Oropharyngeal Cancer: Clinical Guidelines

List of Abbreviations

AUC (area under ROC curve) – area under the ROC curve

ECOG – Eastern Cooperative Oncology Group performance status scale

ENE – extracapsular nodal extension

IMRT – intensity-modulated radiotherapy (volumetric modulated arc therapy)

QUANTEC – quantitative analyses of normal tissue effects in the clinic

TNM (abbreviation for tumor, nodus, and metastasis) – International staging system for malignant tumors (pT – pathological tumor staging; pN – pathological regional lymph node staging)

VMAT – volumetric modulated arc therapy

IV – intravenous

HPV – human papillomavirus

DNA – deoxyribonucleic acid

IHC – immunohistochemical

ICT – induction chemotherapy

CT – computed tomography

RT – radiotherapy

LNs – lymph nodes

mAb – monoclonal antibody

MRI – magnetic resonance imaging

PCT – polychemotherapy

PCR – polymerase chain reaction

RNA – ribonucleic acid

LoD – level of reliability of evidence

US – ultrasound examination

LoR – level of conviction of recommendation

CCF – chronic cancer pain syndrome

CRT – chemoradiotherapy

Terms and Definitions

Anterior wall of the oropharynx – base of the tongue, valleculae.

Lateral walls of the oropharynx – palatine tonsils, tonsillar fossae, anterior and posterior palatine arches, glossotonsillar sulci.

Posterior wall of the oropharynx – right and left sides.

Superior wall of the oropharynx – inferior surface of the soft palate, uvula.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Oropharyngeal cancer – a malignant tumor originating from the non-keratinizing epithelium elements of the oropharynx [1].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The main etiological factors for the development of oropharyngeal cancer are considered to be [1, 2]:

• bad habits: smoking, especially combined with the consumption of high-proof alcohol, chewing various mixtures (naswar, betel, etc.);

• human papillomavirus (HPV), particularly types 16 and 18.

1.3 Epidemiology of the Disease or Condition

In 2021, 2,833 cases of malignant neoplasms of the oropharynx were registered in Russia, with the standardized incidence rate being 2.3 cases per 100,000 population in males and 0.40 cases per 100,000 population in females. The disease is most frequently detected at the age of 40 to 74 years. The peak incidence rate occurs at the age of 65–69 years (5.9 cases per 100,000 population). Annually, the number of newly diagnosed cases of malignant neoplasms of the oropharynx increases by an average of 3.1% [1, 3].

1.4 Features of Coding the Disease or Condition

ICD-10 Coding

C01 – Malignant neoplasm of base of tongue

C02.4 – Malignant neoplasm of lingual tonsil

C05.1 – Malignant neoplasm of soft palate

C05.2 – Malignant neoplasm of uvula

Malignant neoplasm of tonsil (C09):

C09.0 Malignant neoplasm of tonsillar fossa

C09.1 Malignant neoplasm of tonsillar pillar (anterior or posterior)

C09.8 Overlapping lesion of tonsil

C09.9 Malignant neoplasm of tonsil, unspecified

Malignant neoplasm of oropharynx (C10):

C10.0 Malignant neoplasm of vallecula

C10.1 Malignant neoplasm of anterior surface of epiglottis C10.2 Malignant neoplasm of lateral wall of oropharynx

C10.3 Malignant neoplasm of posterior wall of oropharynx

C10.4 Malignant neoplasm of branchial cleft

C10.8 Overlapping lesion of oropharynx

C10.9 Malignant neoplasm of oropharynx, unspecified

Neoplasm of uncertain or unknown behavior of oral cavity and digestive organs (D37)

D37.0 Lip, oral cavity and pharynx

International Classification of Diseases for Oncology (ICD-O, 4th Edition, 2010): Classification of Oropharyngeal Tumors

Malignant epithelial tumors:

• 8070/3 Squamous cell carcinoma, NOS

• 8051/3 Verrucous carcinoma, NOS

• 8083/3 Basaloid squamous cell carcinoma

• 8052/3 Papillary squamous cell carcinoma

• 8074/3 Spindle cell squamous cell carcinoma

• 8075/3 Adenoid squamous cell carcinoma

• 8560/3 Adenosquamous carcinoma

• 8082/3 Lymphoepithelial carcinoma

1.5 Classification of the disease or condition

The stage of spread of epithelial malignant tumors of the oropharynx is presented in the 8th edition of the TNM staging system for cancer by the AJCC and takes into account HPV status.

The T category includes the following grades:

* Note: Extension of the tumor to the mucosa of the lingual surface of the epiglottis when the primary site is at the base of the tongue and lingual valleculae does not constitute invasion of the larynx.

The N category indicates the presence or absence of regional lymph node (LN) metastases.

Clinical staging of regional lymph nodes (cN) in p16-negative oropharyngeal cancer:

Pathomorphological staging of regional lymph node collectors (pN) in p16-negative oropharyngeal cancer:

*Tumor extension into the mucosa of the lingual surface of the epiglottis, when the primary tumor is located in the tongue base and lingual valleculae, does not indicate laryngeal involvement.

The N category indicates the presence or absence of regional lymph node metastases

Clinical staging of regional lymph node basins (cN) in p16-positive oropharyngeal cancer*:

*Information on ENE+ should be reported separately in order to determine the parameters for chemoradiotherapy, if administered.

Pathomorphological staging of regional lymph node basins (pN) in p16-positive oropharyngeal cancer*:

*Information on ENE+ should be reported separately in order to determine the parameters for chemoradiotherapy, if administered.

The M category describes the presence or absence of distant metastases:

M0 No distant metastases

M1 Distant metastases present

Table 1. Stage grouping

1.6 Clinical presentation of the disease or condition

Clinical manifestations of oropharyngeal cancer depend on the extent, location, and growth pattern of the tumor (exophytic, ulcerative, infiltrative). The clinical picture includes early, advanced, and neglected (far-advanced) stages. Palatine tonsil cancer is the most common (64%). In the early stage, patients typically present with complaints of discomfort during swallowing and pain, which initially may be interpreted as "tonsillitis" for which unsuccessful anti-inflammatory treatment is performed. Upon examination, a dense, nodular infiltrate with ulceration is most frequently revealed. The tumor occupies the affected tonsil and may spread to surrounding tissues and organs (retromolar region, tongue base, soft palate, faucial pillars). Pain may radiate to the ear and the corresponding part of the head. Necrotic processes occurring within the tumor exacerbate inflammation, resulting in halitosis and trismus. Oropharyngeal cancer is characterized by a high metastatic potential. Regional lymph node involvement is observed in 77–80% of patients. Metastases are usually located in the upper deep jugular chain, submandibular, and retropharyngeal LNs, and often have an infiltrative character. The onset of neck metastases may precede the clinical manifestations of the primary tumor. When cancer is located at the base of the tongue, observed in 20.8% of patients, tongue mobility is impaired, severe radiating pain occurs, and swallowing is impaired. In some cases, tumors of the tonsil and tongue base can reach a large size, causing only a feeling of "discomfort" when swallowing. Soft palate cancer is diagnosed in 9.1% of patients, most frequently located in the uvula area and along the free edge; as the muscles become infiltrated, the acts of swallowing and speech are impaired. Cancer of the posterior pharyngeal wall occurs rarely (5.2%); the tumor rapidly spreads through the pharynx and to underlying structures. Distant metastases of oropharyngeal cancer occur in 14–30% of patients and can be localized in the lungs, bones, and other organs [4, 5].

2. Diagnostics, medical indications and contraindications for diagnostic methods

The diagnosis is established based on:

1. anamnestic data, specifically the presence of a neoplasm refractory to conservative treatment for 2–3 weeks;

2. physical examination, including a thorough clinical inspection, palpation of the mass, adjacent tissues, and regional lymph nodes (LNs);

3. cytological examination of the primary tumor (cytological examination of upper respiratory tract discharge and imprints, cytological examination of smears from the upper respiratory tract mucosal surface, cytological examination of upper respiratory tract tissue micro preparations), cytological examination of lymph node biopsy specimens (enlarged or suspicious), cytological examination of lymph node tissue preparation;

4. pathological examination of biopsy (surgical) material;

5. instrumental examinations, including ultrasound (US) of the neck, ultrasound of soft tissues (one anatomical zone), fibrolaryngoscopy, esophagogastroduodenoscopy, computed tomography (CT) of the facial skull and neck with intravenous bolus contrast enhancement / magnetic resonance imaging (MRI) of the facial skull and neck with intravenous contrast enhancement, positron emission tomography combined with computed tomography (PET-CT) with tumor-tropic radiopharmaceuticals with contrast enhancement, as clinically indicated.

2.1 Complaints and Anamnesis

Comments: Risk factors to highlight include harmful lifestyle habits (smoking, consumption of strong alcoholic beverages), occupational hazards, and chronic infection (chronic pharyngitis, tonsillitis, frequent tonsillitis, human papillomavirus [HPV]). When determining smoking history, it is advisable to use the pack-years metric, which accounts for cumulative exposure based on the duration and intensity of smoking.

2.2 Physical Examination

2.3 Laboratory Diagnostics

Comment: The surrogate marker for HPV association specified in the international classification for staging and mandatory for testing is the expression of the p16 protein in tumor cells by the IHC method

Comment: Routine pathological examination should report the following parameters:

• tumor size;

• depth of tumor invasion;

• histological structure of the tumor;

• tumor differentiation grade;

• presence of lymphovascular and perineural invasion (negative results must also be stated);

• pT;

• pN (indicating the total number of examined and involved LNs, and evidence of extranodal extension of the tumor);

• status of resection margins (negative results or close resection margins must also be stated);

• HPV 16 and 18 status in the tumor using PCR, IHC, and/or in situ hybridization.

Several methods are used in clinical practice. One of them is the determination of p16 expression using IHC analysis. The p16 protein is a surrogate biomarker that significantly correlates with HPV status and is determined by detecting E6/E7 messenger RNA (mRNA) expression. Other methods for detecting HPV are PCR and in situ hybridization. The sensitivity of IHC and PCR is high, but in situ hybridization has the highest specificity. An analysis of HPV diagnostic methods showed that the sensitivity and specificity of IHC range from 94 to 97% and 83 to 84%, respectively, whereas the sensitivity and specificity of in situ hybridization for detecting HPV type 16 are 85–88% and 88–95%, respectively. The lower specificity of IHC may be due to the fact that some p16-positive tumors lack HPV DNA. The lower sensitivity of in situ hybridization may be due to the presence of other HPV types in the tumor. Considering the differences in sensitivity and specificity of various methods for diagnosing HPV infection status, they can be used in combination [6, 7, 8, 9, 10].

2.4 Instrumental Diagnostics

Comment: regional metastases are diagnosed in 80% of cases and are often the first clinical manifestation of the disease. *Lymph nodes with altered structure according to medical imaging data should be considered suspicious.

Comment: in the presence of cranial nerve involvement symptoms, MRI is the preferred method for assessing perineural invasion [2]. CT has higher diagnostic accuracy for evaluating cortical bone destruction [2].

Comment: if chest CT cannot be performed, targeted chest radiography is indicated

Comment: If PET-CT or CT is not feasible, targeted chest radiography and abdominal ultrasound are indicated for tumor staging and treatment planning [2].

Comment: if brain MRI is not feasible, contrast-enhanced brain CT is indicated [2].

2.4.1 Planning of radiotherapy and chemoradiotherapy

Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C, Level of Evidence – 5

Comment: if MRI—which provides superior soft tissue and spatial visualization—is not available, planning of radiotherapy (RT) and chemoradiotherapy (CRT) requires contrast-enhanced CT of the facial skull and contrast-enhanced neck CT, or PET-CT with a tumor-tropic radiopharmaceutical (fluorodeoxyglucose [18F]) with contrast enhancement

2.4.2 Evaluation of antitumor treatment efficacy

2.4.3 Follow-up monitoring

Comment: if CT is not feasible, targeted chest radiography is indicated

GCP CGrading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment: if PET-CT or contrast-enhanced CT of the chest and abdomen is not feasible, targeted chest radiography and comprehensive abdominal ultrasound are indicated.

2.5 Other Procedures

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

The prescription and use of medicinal products specified in the clinical guideline are aimed at providing the patient with clinically effective and safe medical care; therefore, their prescription and use in a specific clinical situation are determined in accordance with the instructions for use of specific medicinal products, implementing the precautions described in the instructions, and dose adjustments may also be made taking into account the patient's condition.

Specialized anti-tumor treatment for patients with oropharyngeal cancer should be carried out taking into account the experience and equipment of the clinic, as well as patient preferences in light of expected outcomes both in terms of oncological efficacy and preservation of patients' quality of life.

In early stages (T1-2N0M0), preference should be given to single-modality treatment (either RT or surgery). Treatment that subsequently requires a combination with another modality (adjuvant RT/CRT, salvage surgery) is undesirable due to a decrease in patients' quality of life resulting from the cumulative side effects of each modality.

In advanced oropharyngeal cancer, the priority is to increase patient survival through either standalone or combined/multimodality treatment. Treatment of patients with recurrent disease should aim to increase survival and improve quality of life by employing the most effective methods, taking into account prior treatment, as well as the patient's age and performance status.

3.1. General principles of treatment depending on the stage

• For p16-negative T1–2, N0 cancer with no distant metastases, if conservative treatment is chosen, it is recommended to administer standalone RT to increase survival and preserve quality of life [23].

GCR BLEL 2Grade of Recommendation – B (Level of Evidence – 2)

• For p16-negative T1–2, N1 cancer with no distant metastases, if conservative treatment is chosen, it is recommended to administer concurrent CRT to increase survival and preserve quality of life [24].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comment: If residual tumor and/or metastatic lymph nodes persist after conservative treatment, surgical intervention is indicated. In case of complete regression of metastatic nodes following conservative treatment methods, active surveillance is indicated [2, 25, 26, 27].

Comment: If unfavorable histological factors are identified, such as a close resection margin (less than 5 mm), perineural/perivascular/lymphatic invasion, pT3/pT4, pN2 or pN3, or metastasis located in level IV or V cervical lymph nodes, adjuvant RT or concurrent CRT is indicated (CRT is discussed on an individual basis in the presence of two or more of these unfavorable factors, taking into account the patient's age and performance status).

If routine pathomorphological examination of the surgical specimen reveals such an unfavorable histological feature as extracapsular extension of the metastasis/metastases, adjuvant concurrent CRT is indicated.

In the presence of positive resection margins, repeat surgery (if feasible) or concurrent CRT is indicated [2, 25, 26, 27, 30].

Level of Recommendations – BLevel of Evidence – 2Level of Recommendations – B (Level of Evidence – 2)

Comment: If residual tumor and/or metastatic lymph nodes persist after conservative treatment, surgical intervention is indicated. In case of complete regression of metastatic nodes following conservative treatment methods, active surveillance is indicated [2, 25, 26, 27].

• For p16-negative T3, T4, N0–1 cancer, in the presence of contraindications to RT/CRT or patient refusal, it is recommended to perform surgical intervention with unilateral or bilateral neck dissection to increase survival [2].

Level of Recommendations – CLevel of Evidence – 5Level of Recommendations – C (Level of Evidence – 5)

Comment: if no additional prognostically unfavorable factors are identified in the routine pathomorphological examination of the biopsy (surgical) material (resected specimen) after surgical treatment, adjuvant radiation therapy is indicated.

If unfavorable histological factors are identified, such as a close resection margin (less than 5 mm), perineural/perivascular/lymphatic invasion, pT3/pT4, pN2 or pN3, or metastasis located in level IV or V cervical lymph nodes, adjuvant RT or concurrent CRT is indicated (CRT is discussed on an individual basis in the presence of two or more of these unfavorable factors, taking into account the patient's age and performance status).

If routine pathomorphological examination of the surgical specimen reveals such an unfavorable histological feature as extracapsular extension of the metastasis/metastases, adjuvant concurrent CRT is indicated.

In the presence of positive resection margins, repeat surgery (if feasible) or concurrent CRT is indicated [2, 25, 26, 27.]. Level of Recommendations – B (Level of Evidence – 2)

Comment: If residual tumor and/or metastatic lymph nodes persist after conservative treatment, surgical intervention is indicated. In case of complete regression of metastatic nodes following conservative treatment methods, active surveillance is indicated [25, 26, 27].

• For p16-negative T3, T4, N2–3 cancer, in the presence of contraindications to RT/CRT or patient refusal, it is recommended to perform surgical intervention with unilateral or bilateral neck dissection to increase survival [2].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment: If no prognostically unfavorable factors are identified in the routine pathomorphological examination of the resected specimen after surgical treatment, adjuvant radiation therapy is indicated.

If unfavorable histological factors are identified, such as a close resection margin (less than 5 mm), perineural/perivascular/lymphatic invasion, pT3/pT4, pN2 or pN3, or metastasis located in level IV or V cervical lymph nodes, adjuvant RT or concurrent CRT is indicated (CRT is discussed on an individual basis in the presence of two or more of these unfavorable factors, taking into account the patient's age and performance status).

If unfavorable histological features such as extracapsular extension of metastasis/metastases and/or positive resection margins are identified, adjuvant concurrent CRT is indicated [2, 25, 46, 27, 30].

Level of Recommendations – BLevel of Evidence – 2Level of Recommendations – B (Level of Evidence – 2)

• For p16-positive T1–2, N0 cancer, if conservative treatment is chosen, it is recommended to administer standalone RT to increase survival and preserve quality of life [2, 12, 28, 33].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment: If residual tumor and/or metastatic lymph nodes persist after conservative treatment, surgical intervention is indicated. In case of complete regression of metastatic nodes following conservative treatment methods, active surveillance is indicated [2, 25, 26, 27].

Comment: if unfavorable histological features such as a close resection margin, perineural/perivascular/lymphatic invasion, pT3/pT4, a single positive node > 3 cm or multiple positive nodes, or level IV or V lymph node involvement are identified, adjuvant RT or concurrent CRT is indicated (CRT is discussed on an individual basis in the presence of two or more of these unfavorable factors, taking into account the patient's age and performance status).

If routine pathomorphological examination of the surgical specimen reveals such an unfavorable histological feature as extracapsular extension of the metastasis/metastases +/- positive resection margins, adjuvant concurrent CRT is indicated.

In the presence of a positive resection margin, repeat surgery (if feasible) or concurrent CRT is indicated [2, 25, 26, 27, 30].

• For p16-positive T0–2, N1 cancer (single ipsilateral node ≤ 3 cm), if conservative treatment is chosen, it is recommended to administer CRT to increase survival, or standalone RT to reduce treatment toxicity (standalone RT is discussed when using IMRT/VMAT, taking into account the clinic's experience and equipment) [2, 35, 36]

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment: If residual tumor and/or metastatic lymph nodes persist after conservative treatment, surgical intervention is indicated. In case of complete regression of metastatic nodes following conservative treatment methods, active surveillance is indicated [2, 25, 26, 27].

• For p16-positive T1–2, N0–1 cancer (one ipsilateral node ≤ 3 cm), if surgical treatment is chosen, it is recommended to perform primary tumor resection +/- ipsilateral (for lateralized tumor process) or bilateral (for central tumor localization or extension across the midline) neck dissection to increase survival [37].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment: if adverse histological features are identified, such as close resection margin, perineural/perivascular/lymphatic invasion, pT3/pT4, a single positive node > 3 cm or multiple positive nodes, level IV or V lymph node involvement, adjuvant RT or concurrent CRT is indicated (CRT is discussed individually in the presence of two or more of these adverse factors, taking into account the patient's age and performance status)

If routine pathomorphological examination of the surgical specimen reveals such an unfavorable histological feature as extracapsular extension of the metastasis/metastases +/- positive resection margins, adjuvant concurrent CRT is indicated.

If a positive resection margin is present, repeat surgery is indicated, if feasible, or concurrent CRT [2, 25, 26, 27, 30].

• For p16-positive T2, N1 (1 ipsilateral metastatic lymph node > 3 cm or 2 or more ipsilateral metastatic lymph nodes ≤ 6 cm on one side) or T0–2, N2 or T3, N0–2 cancer, it is recommended to administer concurrent CRT to increase survival [2, 12, 24, 33].

GCR BLEL 2Grade of Recommendation – B (Level of Evidence – 2)

• For p16-positive T2, N1 (1 ipsilateral metastatic lymph node > 3 cm or 2 or more ipsilateral metastatic lymph nodes ≤ 6 cm on one side) or T0–2, N2 or T3, N0–2 cancer, if conservative treatment is chosen, it is recommended to administer induction chemotherapy followed by RT/CRT to increase survival [12, 24, 33].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment: If residual tumor and/or metastatic lymph nodes persist after conservative treatment, surgical treatment is indicated. In case of complete regression of metastatic nodes following conservative treatment, active surveillance is indicated [2, 25, 26, 27].

• For p16-positive T2, N1 (1 ipsilateral metastatic lymph node > 3 cm or 2 or more ipsilateral metastatic lymph nodes ≤ 6 cm on one side) or T0–2, N2 or T3, N0–2 cancer, if surgical treatment is chosen, it is recommended to perform primary tumor resection and ipsilateral (for cN0–3 on one side) or bilateral (for cN2–3 on both sides) neck dissection to increase survival [2].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comment: if adverse histological features are identified, such as close resection margin, perineural/perivascular/lymphatic invasion, pT3/pT4, a single positive node > 3 cm or multiple positive nodes, level IV or V lymph node involvement, adjuvant RT or concurrent CRT is indicated (CRT is discussed individually in the presence of two or more of these adverse factors, taking into account the patient's age and performance status).

If routine pathomorphological examination of the surgical specimen reveals such an unfavorable histological feature as extracapsular extension of the metastasis/metastases +/- positive resection margins, adjuvant concurrent CRT is indicated.

If a positive resection margin is present, repeat surgery is indicated, if feasible, or concurrent CRT [2, 25, 26, 27, 30].

• For p16-positive T0–3, N3 or T4, N0–3 cancer, concurrent CRT is recommended to increase survival [12, 31, 38].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment: If residual tumor and/or metastatic lymph nodes persist after conservative treatment, surgical treatment is recommended. In case of complete regression of metastatic nodes following conservative treatment, active surveillance is indicated [2, 25, 26, 27].

If adverse histological features are identified, such as close resection margin, perineural/perivascular/lymphatic invasion, pT3/pT4, a single positive node > 3 cm or multiple positive nodes, level IV or V lymph node involvement, adjuvant RT or concurrent CRT is indicated (CRT is discussed individually in the presence of two or more of these adverse factors, taking into account the patient's age and performance status)

If routine pathomorphological examination of the surgical specimen reveals such an unfavorable histological feature as extracapsular extension of the metastasis/metastases +/- positive resection margins, adjuvant concurrent CRT is indicated.

If a positive resection margin is present, repeat surgery is indicated, if feasible, or concurrent CRT [2, 25, 26, 27, 30].

LoE BGoE 3Level of Evidence – B (Grade of Recommendation – 3).

Local recurrence or residual tumor without prior RT.

• In case of local recurrence or residual tumor without prior RT, for a resectable process, surgery is recommended to improve survival [2].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment: if adverse histological features are identified, such as close resection margin, perineural/perivascular/lymphatic invasion, pT3/pT4, pN2 or pN3, adjuvant RT or concurrent CRT is indicated (CRT is discussed individually in the presence of two or more of these adverse factors, taking into account the patient's age and performance status).

If postoperative routine pathomorphological examination of the surgical specimen reveals such adverse histological features as extracapsular extension of metastasis/es and/or positive resection margins, adjuvant concurrent CRT is indicated [2, 12, 26, 29, 30].

• In case of local recurrence or residual tumor without prior RT, if the process is resectable and surgery is declined, concurrent CRT is recommended to increase survival [2].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

• In case of local recurrence or residual tumor without prior RT, if the process is unresectable, chemotherapy is recommended with subsequent discussion of potential RT/CRT to increase survival [2].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment: If residual tumor and/or metastatic lymph nodes persist after conservative treatment, surgical treatment is indicated. In case of complete regression of metastatic nodes following conservative treatment, active surveillance is indicated [2, 27, 29, 30].

• In case of local recurrence or residual tumor after RT, if the tumor is resectable, surgery is recommended to improve survival [2].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

• In case of local recurrence or residual tumor after RT, if the tumor is unresectable, discussion of an individualized plan with potential drug therapy, re-irradiation/concurrent CRT, or palliative care is recommended to improve survival [2].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comments: Drug therapy section.

The feasibility of re-irradiation is discussed when the patient's general condition is 0–1 on the ECOG scale and not earlier than 6 months (preferably not earlier than 2 years) after prior irradiation [39]

• For patients with local recurrence or residual tumor with distant metastases, to assess survival and reduce the risk of complications, treatment selection is recommended based on the ECOG performance status [2]:

— for an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, polychemotherapy (PCT) or monotherapy is recommended;

— for an ECOG performance status of 2, monochemotherapy or palliative care is recommended;

— for an ECOG performance status of 3, palliative care is recommended.

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

3.2. Principles of surgical treatment

All patients must be evaluated prior to treatment by a head and neck surgical oncologist, who should take the following steps: review the adequacy of biopsy material, staging, and imaging of the tumor process (CT, MRI) to determine the extent of tumor spread; rule out synchronous primary tumors; assess the current performance status and feasibility of surgical treatment; if initial treatment was non-surgical, develop a prospective follow-up plan that includes appropriate dental, nutritional, and lifestyle evaluations, as well as interventions and any other additional studies necessary for complete rehabilitation. For patients undergoing elective surgery, the surgical intervention, the margins of the clinically defined tumor with tumor-free surgical margins must be planned out. Surgical intervention should not be modified based on the pre-treatment clinical response observed at the current examination (tumor regression), except for cases of tumor progression that necessitate a more extensive operation to encompass the entire tumor during definitive resection [2, 40].

• Surgical treatment is not recommended for patients with oropharyngeal malignancies in the following cases: T4b stage, direct tumor extension from regional lymph nodes to the skin, direct extension to mediastinal structures, prevertebral fascia, or cervical vertebrae due to unresectability of the process, intraoperative and postoperative risks, low efficacy, and low probability of a radical surgical outcome [2].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment: Surgical removal should be planned based on the extent of the primary tumor established during clinical examination and careful interpretation of relevant radiographs. Transoral resections using a CO2 laser under optical magnification or robot-assisted surgery are preferred. If the tumor is adjacent to a motor or sensory nerve, perineural invasion cannot be excluded. In this situation, the nerve should be dissected proximally and distally and resected to obtain a clear margin. It has been confirmed that frozen section analysis (urgent pathomorphological examination of the surgical specimen) of the proximal and distal nerve margins is recommended to obtain tumor-free tissue.

• In patients with oropharyngeal malignancies who are candidates for surgery, it is recommended to achieve an R0 resection status to reduce the risk of tumor recurrence [41].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comment: Adequate removal is defined as a distance of ≥1.5 cm from the resection margin to the macroscopically visible tumor or a negative frozen section margin. In general, frozen section evaluation is usually performed intraoperatively. If the macroscopically tumor-free zone at the resection margin is <1.5 cm, the line of resection cannot be determined due to unclear tumor boundaries, or residual tumor is suspected. A detailed description of the resection margin must be included in the operative report. Margins can be assessed from the resected specimen or, alternatively, from the tumor bed with proper orientation. A clear margin is defined as a distance of ≥5 mm from the invasive tumor front to the resection margin. A close margin is defined as a distance of <5 mm from the invasive tumor front to the resection margin. The primary tumor should be marked so that the pathologist can adequately assess the orientation of the specimen. Neck dissection specimens must be oriented or sectioned sequentially to determine the level of lymph nodes included in the dissection zone. Surgical defects should be repaired using conventional techniques at the surgeon's discretion. Primary closure is recommended whenever possible, but without compromising wide tumor-free margins. Plastic closure using local/regional flaps, free flaps, split-thickness skin grafts, or other flaps with or without mandibular reconstruction is performed at the surgeon's discretion.

Lymph node dissection.

• When the primary tumor is localized in the oropharynx and a surgical treatment approach is chosen, selective neck dissection of levels II–IV is recommended to improve patient survival [42].

LEI CQOE 4Level of Evidence – C (Quality of Evidence – 4)

Comments: Prophylactic neck dissection (levels II–IV) is mandatory for T3–T4 primary tumors, as well as for primary tumors located in the tonsil and tonsillar fossa starting from T1–T2 stage, since the risk of regional lymph node metastasis reaches 50% [42]. Removal of lymph nodes at levels II–V is advisable if one of the following factors is present:

· palpable metastasis in level IV or V;

· regional metastasis >6 cm in diameter;

· large multiple metastases (>3 cm);

· pronounced extracapsular extension involving critical anatomical structures (sternocleidomastoid muscle, internal jugular vein, common carotid artery);

· recurrent disease

3.3. Principles of radiotherapy

All patients must be evaluated prior to treatment by a radiation oncologist, preferably one specializing in head and neck tumors, who should take the following steps: review the adequacy of morphological verification, staging, and imaging of the tumor process (CT, MRI) to determine the extent of tumor spread; rule out synchronous primary tumors; assess the current performance status and feasibility of radiotherapy/chemoradiotherapy; develop a prospective patient management plan that includes sanitation of the oropharyngeal area, including dental examination, provision of adequate nutrition, pain management, wound healing, and other measures necessary for adequate and timely rehabilitation. For patients receiving chemotherapy/chemoradiotherapy, the tactics for administering full-dose anticancer therapy within optimal timeframes must be mapped out.

Radiotherapy as primary or adjuvant treatment should be performed in specialized centers with appropriate equipment and expertise in treating oropharyngeal cancer [43].

A deep understanding of anatomy, clinical presentation, and imaging of specific disease manifestations is required. High-precision radiotherapy techniques are preferred, such as IMRT (intensity-modulated radiotherapy) and VMAT (volumetric modulated arc therapy). Proton therapy is considered in cases of significant normal tissue dose constraints. 3D conformal radiotherapy is also acceptable.

The optimal approach in clinical practice is to deliver the planned doses of ionizing radiation to the target volume while minimizing the dose to organs at risk. It is acceptable to discuss volume reduction by excluding vital structures free from tumor involvement at the time of radiotherapy planning, provided that the dose limits for these structures would otherwise exceed QUANTEC criteria (quantitative analyses of normal tissue effects in the clinic) [41]. The radical radiation dose volume should not be modified based on the clinical response observed prior to radiotherapy (after induction chemotherapy), except in cases of tumor progression. Anatomical changes during the course of radiotherapy (e.g., rapid tumor shrinkage, significant weight loss) may necessitate repeat diagnostic imaging and treatment replanning (adaptation).

• Definitive radiotherapy is recommended for the primary lesion and clinically apparent regional metastases (high-risk area) at a dose of 66–70 Gy (2.0–2.2 Gy/fraction) daily, Monday through Friday, for 6–7 weeks; and for the locoregional area (intermediate/low-risk area), including regional lymph nodes, at a dose of 44–50 Gy (2.0 Gy/fraction) or 54–63 Gy (1.6–1.8 Gy/fraction) to improve survival rates [2, 17, 18, 19].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment: In specialized centers with appropriate equipment and experience in treating oropharyngeal cancer, accelerated radiotherapy is acceptable up to a total dose of 66–70 Gy (2.0 Gy/fraction, 6 fractions per week). When using 3D conformal radiotherapy, conventional fractionation is strongly recommended (a fractional dose of 2 Gy up to a total dose of 50 Gy to the locoregional area and up to a total dose of 70 Gy to the primary tumor and clinically apparent regional metastases, respectively.

For localized oropharyngeal lesions (T1–2N0), individually planned brachytherapy is also an option [44].

• Concurrent chemoradiotherapy (CCRT) as a definitive treatment is recommended for the primary tumor and clinically apparent regional metastases (high-risk area) at a dose of 70 Gy (2.0 Gy/fraction) daily from Monday to Friday for 6–7 weeks; for the locoregional area (intermediate/low-risk area), including regional lymph nodes, at a dose of 44–50 Gy (2.0 Gy/fraction) or 54–63 Gy (1.6–1.8 Gy/fraction), taking into account the risk of subclinical spread and the radiotherapy technique [2, 17, 18, 19].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comment: The standard approach is the combination of radiotherapy with cisplatin** at a dose of 100 mg/m² with hyperhydration on days 1, 22, and 43 of radiotherapy (recommended total dose during radiotherapy is 300 mg/m²). Radiotherapy combined with #carboplatin** at a dose of 70 mg/m² and #fluorouracil** at a dose of 600 mg/m² on days 1–4 every 3 weeks is also possible (considering the high toxicity of this regimen) [45, 46].

Following induction chemotherapy, cetuximab** or carboplatin** is recommended as an alternative to cisplatin**, taking into account the patient's tolerability of CCRT and general physical status. Cetuximab** is administered at a loading dose of 400 mg/m² one week prior to radiotherapy, followed by a maintenance dose of 250 mg/m² weekly during radiotherapy.

Omitting platinum-based CCRT regimens in favor of cetuximab** is advisable in cases of a high risk of failing/not completing the definitive CCRT plan and a high risk of platinum toxicity (glomerular filtration rate <50–60 ml/min, patient age >65 years, severe concomitant renal, cardiovascular, neurological, or hepatic pathology, and/or a poor performance status (ECOG >1)) [36, 47].

The benefit of non-conventional dose fractionation schedules in concurrent chemoradiotherapy has not been confirmed [48].

• Postoperative radiotherapy is recommended to the bed of the removed primary tumor and regional metastases at a dose of 60–66 Gy (2.0 Gy/fraction) daily from Monday to Friday for 6–6.5 weeks, and to the locoregional area, including unaffected regional lymph nodes, at 44–50 Gy (2.0 Gy/fraction) or 54–63 Gy (1.6–1.8 Gy/fraction), taking into account the risk of subclinical spread and the radiotherapy technique [2, 17, 18, 19].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comments: The preferred interval after surgery is ≤6 weeks and should not exceed 3 months. A total dose of 66 Gy is delivered to the high-risk area—the region of a positive resection margin or extracapsular extension of a metastasis.

• Postoperative concurrent chemoradiotherapy is recommended to the bed of the removed primary tumor and regional metastases at a dose of 60–66 Gy (2.0 Gy/fraction) daily from Monday to Friday for 6–6.5 weeks, and to the locoregional area, including unaffected regional lymph nodes, at 44–50 Gy (2.0 Gy/fraction) or 54–63 Gy (1.6–1.8 Gy/fraction), taking into account the risk of subclinical spread and the radiotherapy technique [2, 17, 18, 19, 30].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

Comments: Concurrent platinum-based chemotherapy is recommended, preferably cisplatin** at a dose of 100 mg/m² every 3 weeks [30]. In the presence of comorbidities that preclude concurrent platinum-based chemoradiotherapy (chronic renal failure, severe heart disease, etc.), replacing platinum compounds with cetuximab** during radiotherapy is preferred [47].

The preferred interval after surgery is ≤6 weeks and should not exceed 3 months. A total dose of 66 Gy is delivered to the high-risk area—the region of a positive resection margin or extracapsular extension of a metastasis.

The benefit of non-conventional dose fractionation schedules in concurrent chemoradiotherapy has not been confirmed [47].

• Palliative radiotherapy is recommended for the palliation or prevention of locoregional symptoms when radical treatment with standard radiotherapy is not feasible. Individualized radiotherapy planning aimed at minimizing treatment toxicity may be chosen, including doses of 50 Gy (2.5 Gy/fraction) and 30 Gy (3 Gy/fraction) [49, 50, 51, 52].

Level of Recommendations – CLevel of Evidence – 4Level of Recommendations – C (Level of Evidence – 4)

3.4 Principles of systemic chemotherapy

• When choosing induction chemotherapy as the primary treatment method for all patients with oropharyngeal cancer to improve survival, it is recommended to use the following chemotherapy regimen:

Preferred: docetaxel** 75 mg/m² on day 1 + cisplatin** 75 mg/m² on day 1 + #fluorouracil** 1000 mg/m²/day on days 1–4, for a total of 2–3 cycles of chemotherapy at 3-week intervals [53].

LoE CGoE 5Level of Evidence – C (Grade of Recommendation – 5

As an alternative induction chemotherapy regimen, the following scheme may be considered: #paclitaxel** 175 mg/m2 on day 1 + cisplatin** 100 mg/m2 on day 2 + #fluorouracil** 500 mg/m2 continuous infusion on days 2–6, for a total of 3 cycles of chemotherapy at 3-week intervals [54, 55].

GCR BLEL 2Grade of Recommendation – B (Level of Evidence – 2)

• As definitive concurrent chemoradiotherapy following induction, it is recommended that all patients with oropharyngeal cancer receive chemotherapy including cisplatin** 100 mg/m² once every 3 weeks to improve survival [56].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comment: Given the high toxicity of this concurrent therapy regimen, weekly administration of carboplatin** AUC 1.5 or cetuximab** 400 mg/m² one week prior to radiotherapy and 250 mg/m² weekly during radiotherapy is an option. In the presence of comorbidities that preclude concurrent platinum-based chemoradiotherapy (chronic renal failure, severe heart disease, etc.), replacing platinum drugs with cetuximab** during radiotherapy is preferred - [47].

• For patients with a local unresectable recurrence or residual tumor after prior radiotherapy, as well as in the presence of distant metastases, mono- or polychemotherapy is recommended to increase survival, see Table 1 [2].

Table 1. Medical therapy regimens for squamous cell carcinoma of the head and neck [51].

¹ For patients with an ECOG performance status of 2.

² Suboptimal treatment regimens; can be used only in case of absolute contraindications to anti-EGFR mAbs.

³ In the 2nd and subsequent lines of therapy for platinum-resistant tumors. Can be prescribed regardless of PD-L1 expression level.

⁴As first-line therapy in the presence of PD-L1 CPS > 20. In case of progression during or after platinum-based chemotherapy, with a TPS level ≥ 50%. The recommended duration of use corresponds to the design of registration trials.

⁵As first-line therapy when PD-L1 expression is ≥ 1%.

⁶The regimen corresponds to clinical trials; in case of poor tolerability, the dose should be reduced.

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment: Taking into account the patient's general condition and/or treatment goals, the following drugs or their combinations can be prescribed as first-line therapy (the number of courses is determined by tolerability and treatment efficacy)

3.5. Other treatment modalities

The procedure and recommendations for pain management in malignant neoplasms of the oral cavity correspond to the recommendations presented in the clinical guidelines "Chronic Pain Syndrome (CPS) in Adult Patients Requiring Palliative Medical Care"

Comment: the risk of bleeding is stated in the presence of an ulcerated locally advanced tumor process involving adjacent structures, a cavity in the tumor area or tumor recurrence, proximity of the tumor to the branches of the carotid artery, a non-healing wound, or active bleeding from the tumor.

GCR CLOE 5Grade of Recommendations – C (Level of Evidence – 5).

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• Nutritional and metabolic rehabilitation is recommended to improve survival, reduce the incidence of complications from anticancer treatment, and improve treatment tolerability and patients' quality of life [93].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comments: Nutritional support when planning surgical treatment or radiation therapy is carried out in the presence of at least one of the specified factors: unintentional weight loss over the past 6 months (loss of 5% or more), body mass index <20 kg/m², hypoproteinemia <60 g/l or hypoalbuminemia <30 g/l, impaired ability to take food over the past week. In the case of chemotherapy, the indications are: body mass index <20 kg/m2; weight loss of more than 5% over 6 months; hypoproteinemia <60 g/l or hypoalbuminemia <30 g/l; inability to eat adequately by mouth; moderate to severe enteropathy.

4.1. Rehabilitation during chemotherapy

• For patients with oropharyngeal malignancies receiving chemotherapy, it is recommended to start physical activity early to prevent the onset and progression of sarcopenia, reduce fatigue, improve the quality of life and psychological state of patients receiving adjuvant chemotherapy, and increase exercise tolerance [94].

GOR BLOE 3Grade of Recommendation – B (Level of Evidence – 3).

Comments: Performing a set of exercise therapy including aerobic exercise and Tai Chi elements for 4 months during chemotherapy leads to an increase in forced vital capacity, blood oxygen saturation, muscle strength, range of motion in large joints, and a decrease in body mass index [95].

• To reduce fatigue and increase endurance in patients with oropharyngeal malignancies undergoing chemoradiotherapy, physical rehabilitation is recommended [96].

GCP BLoE 2Grade of Recommendation – B (Level of Evidence – 2).

Comment: A combination of exercise therapy (in the form of moderate-intensity aerobic exercise combined with resistance exercises) and psychological support is used as a comprehensive treatment for fatigue during chemotherapy [94]. In addition, it is advisable to conduct a 6-week course of general medical massage to reduce fatigue during combination treatment [97].

4.2. Rehabilitation during radiotherapy

The success of anticancer treatment and rehabilitation depends on the patient's baseline condition. Thus, risk factors for the early onset and development of severe side effects include exhaustion and a severe psychological state of the patient, older age, comorbidities, injuries to the oral mucosa and pharynx, presence of decayed teeth, severe pain syndrome, smoking, and alcohol intake. Preparation for treatment and adequate patient management is such an important task that the participation of relevant allied specialists as part of a multidisciplinary team (palliative oncologist, nutritionist, dentist, etc.), as well as the scope of supportive care, are indicated in international guidelines as a prerequisite for successful treatment of patients with head and neck tumors.

The management of oropharyngeal cancer patients receiving or having received radiation therapy requires a comprehensive approach including at least three core components of supportive care: wound healing, pain management, and nutritional support, combined with maintaining patient contact and treatment adherence at all stages. It should be noted that supportive care and rehabilitation methods are much more diverse and also imply detoxification therapy, correction of hematological toxicity, antiulcer, antiemetic, and antibiotic therapy, among others. Furthermore, careful post-treatment monitoring of patients and correction of potential delayed side effects of radiation therapy (xerostomia, bone and/or soft tissue necrosis, etc.) are mandatory.

Adequate nutrition and maintenance of water balance are vital. Combating "iatrogenic" malnutrition resulting from radiotherapy (RT) and chemoradiotherapy (CRT) is a crucial task in the successful treatment of patients with head and neck tumors. A special role is played by a balanced dietary intake, which is reflected in maintaining a stable body weight. It should be noted that nutritional support is administered for therapeutic purposes, as the period of RT is characterized by the body's increased need for energy and plastic substrates. In patients without severe dysphagia receiving RT and CRT, oral enteral nutrition is the method of choice. Nutritional therapy should be initiated immediately upon identification of malnutrition or in the absence of adequate oral intake for 7 days.

Level of Evidence: 5 (Grade of Recommendation: C).

Comments: Enteral medical nutrition is initiated when oral dietary intake is inadequate (i.e., less than 60% of total energy requirements for 10 days). A loss of more than 10% of baseline body weight is an indication for enteral nutrition. The optimal option for nutritional support is sip feeding using high-protein formulas (taking into account comorbid conditions, including renal pathology). If adequate oral nutrition is impossible, it should be provided via a nasogastric tube (estimated placement duration up to 3–4 weeks) or via gastrostomy. Parenteral nutrition may also be initiated if necessary. The calculation of the patient's basic requirements focuses on the total amount of energy consumed and the quantitative ratio of various substrates. The required number of calories is most frequently calculated based on energy expenditure, aiming to prevent the escalation of energy deficit [109, 110, 111]. The primary goal of nutritional support is to replenish losses at least at the rate of: protein / amino acids: no less than 1.2 g/kg/day and up to 2 g/kg/day; energy: 25–30 kcal/kg/day [111]. For patients receiving RT and CRT, it is optimal to use formulas enriched with omega-3 fatty acids and dietary fiber, as well as to combine nutritional support with physical exercise.

From the onset of manifestations until the complete resolution of radiation mucositis, the use of topical healing agents is indicated (A01AD11 Other agents for local wound healing (gels, urea solution, ointments, etc.)). Regular oral rinsing with isotonic solution removes food debris and accumulated secretions. Oils (olive, peach, sea buckthorn, or rosehip) are recommended for intraoral applications or nasal instillation. In the presence of pain syndrome, local anesthetics (D04AB: Topical products for joint and muscular pain / local anesthetics) and systemic analgesics (N02B Other analgesics and antipyretics) are used [110]. Pain management should be prescribed in accordance with the WHO analgesic ladder. Opioid analgesics (N02A Opioids) are most frequently required, and attention should be paid to transdermal delivery systems [112].

From the onset of radiation dermatitis and until reactions subside completely, the use of topical wound-healing agents is indicated (D11AX Other dermatological preparations, A11CA01 Retinol (vitamin A)) (gels, dioxomethyltetrahydropyrimidine), as well as sunscreens. The skin must be protected from friction and irritation. Urea cream and oily vitamin A solution are used to combat xerosis. In bio-radiation dermatitis, the use of vitamin K cream is advisable. In the post-radiation period, normal irradiated tissues are very vulnerable and must therefore be handled with care. Invasive diagnostic procedures and biopsies should be avoided in the early stages unless absolutely necessary. Dietary counseling is indicated, combined if necessary with A02B Drugs for peptic ulcer and gastroesophageal reflux disease (GERD) [113, 114]. Trauma, alcohol, smoking, and irritating foods easily induce mucosal ulceration, which is often accompanied by exposure of the mandibular bone with subsequent development of osteomyelitis. A frequent cause of radiation osteomyelitis is tooth extraction in the previously irradiated area; therefore, conservative methods should be prioritized whenever possible, and tooth extraction should only be performed when necessary under antibiotic coverage.

• All patients scheduled for RT/CRT are recommended a dental consultation and examination followed by support at all stages of treatment and rehabilitation [116, 117].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

• All patients receiving/who have received RT/CRT who present with pain are recommended a consultation with an algologist (palliative care physician) to ensure treatment tolerance, adequate rehabilitation, and improved quality of life [118].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5).

• Patients with malignant neoplasms of the oropharynx receiving chemoradiotherapy are recommended an early start of physical exercise to improve quality of life and treatment tolerance [119].

Grade of Recommendation BLevel of Evidence 3Grade of Recommendation – B (Level of Evidence – 3).

5. Prevention and Dispensary Observation

For the purpose of prevention and early diagnosis, attention should be paid to primary symptoms. In particular, the disease is asymptomatic in the early stages. The oropharynx is accessible for examination; upon consulting a primary care specialist (otorhinolaryngologist, general practitioner, dentist, etc.), patients may present with self-detected ulcers, nodular neoplasms, or asymmetry in the oropharynx. Complaints may also include pain and a lump-in-the-throat sensation, numbness, discomfort during swallowing, unexplained fever, neck masses, halitosis, voice changes, chewing difficulties, restricted tongue mobility, and masticatory muscle trismus.

The role of carcinogenic factors must be taken into account: smoking (including secondhand smoke), alcohol consumption, exposure to asbestos, wood dust, petroleum refining products, ionizing radiation, and HPV. Primary care physicians must conduct educational work among the population, explaining the role of these factors in cancer development, and pay attention to precancerous conditions, which include chronic inflammatory diseases, leukoplakia of the oral mucosa, and papillomas.

Dispensary follow-up (Active surveillance)

Comments: The scope of examination includes:

- anamnesis taking and physical examination;

- ultrasound of the neck lymph nodes bilaterally, abdominal and pelvic organs;

- MRI of the facial skull and neck with intravenous contrast/ CT of the facial skull and neck with intravenous bolus contrast enhancement;

- fibrolaryngoscopy;

- targeted chest X-ray every 12 months;

- CT of the chest and abdomen with intravenous bolus contrast enhancement / magnetic resonance imaging of the chest and abdomen with intravenous contrast enhancement as clinically indicated

- Positron emission tomography combined with computed tomography using tumorotropic radiopharmaceuticals with contrast enhancement, as clinically indicated;

- blood thyroid-stimulating hormone (TSH) level testing every 6–12 months if neck irradiation was performed, to assess thyroid function.

The goal of follow-up is early detection of disease progression for the timely initiation of chemotherapy or surgical treatment of resectable metastatic lesions and recurrent tumors, as well as the detection of metachronous head and neck tumors.

6. Organization of Medical Care

Medical care, with the exception of medical care provided as part of clinical trials, in accordance with Federal Law No. 323-FZ dated November 21, 2011, "On the Basics of Protecting the Health of Citizens in the Russian Federation," is organized and provided:

1) in accordance with the regulations on the organization of medical care by types of medical care, approved by the authorized Federal Executive Authority;

2) in accordance with the procedure for the provision of medical care in the profile "oncology", mandatory for implementation throughout the Russian Federation by all medical organizations;

3) based on these clinical guidelines;

4) taking into account the standards of medical care approved by the authorized Federal Executive Authority.

Primary specialized health care is provided by an oncologist and other specialist physicians at an outpatient oncological care center or in a primary oncological office, or in the outpatient department of an oncological dispensary (oncological hospital).

If an oncological disease is suspected or detected in a patient, general practitioners, district general practitioners, general practice physicians (family physicians), specialist physicians, and mid-level medical personnel shall refer the patient in the established manner for consultation at an outpatient oncological care center, a primary oncological office, or the outpatient department of an oncological dispensary (oncological hospital) for the provision of primary specialized health care.

Consultation at an outpatient oncological care center, a primary oncological office, or the outpatient department of an oncological dispensary (oncological hospital) must be performed no later than 5 working days from the date of issuance of the referral for consultation. The oncologist of the outpatient oncological care center (in the absence of an outpatient oncological care center, the oncologist of the primary oncological office or the outpatient department of the oncological dispensary (oncological hospital)) shall arrange for the acquisition of biopsy (surgical) material, as well as other diagnostic tests necessary to establish the diagnosis, including the extent of the oncological process and the stage of the disease.

In the event of the impossibility of acquiring biopsy (surgical) material or performing other diagnostic tests within the medical organization that incorporates the outpatient oncological care center (primary oncological office), the attending physician shall refer the patient to an oncological dispensary (oncological hospital) or to a medical organization providing medical care to patients with oncological diseases.

The timeframe for performing pathological examinations necessary for the histological verification of malignant neoplasms shall not exceed 15 working days from the date of receipt of the biopsy (surgical) material by the pathoanatomical bureau (department).

The timeframes for diagnostic instrumental and laboratory examinations in case of suspected oncological disease shall not exceed the timeframes established in the state guarantee program for the free provision of medical care to citizens, approved by the Government of the Russian Federation.

The diagnosis of an oncological disease is established by an oncologist, and in the case of malignant neoplasms of lymphoid, hematopoietic, and related tissues included in ICD-10 categories C81–C96, also by a hematologist.

The oncologist of the ambulatory cancer care center (primary oncology office) refers the patient to an oncological dispensary (cancer hospital) or another medical organization providing medical care to patients with oncological diseases, including those subordinate to a federal executive authority (hereinafter referred to as a federal medical organization), to clarify the diagnosis (in case of the impossibility of establishing a diagnosis, including the extent of the oncological process and the stage of the disease), determine treatment tactics, and in the presence of medical indications for specialized, including high-tech, medical care.

For oncological diseases included in ICD-10 categories C37, C38, C40–C41, C45–C49, C58, D39, C62, C69–C70, C72, C74, as well as corresponding International Classification of Diseases for Oncology (ICD-O) 3rd edition codes 8936, 906–909, 8247/3, 8013/3, 8240/3, 8244/3, 8246/3, 8249/3, the oncologist of an oncological dispensary (oncological hospital) or other medical organization providing medical care to patients with oncological diseases shall, in order to determine treatment tactics, organize a consultation or a medical board (consilium), including via telemedicine technologies, at federal state budgetary institutions subordinate to the Russian Ministry of Health that provide medical care (hereinafter referred to for the purposes of this Procedure as national medical research centers).

In complex clinical cases, to clarify the diagnosis (in the event of the impossibility of establishing the diagnosis, including the extent of the oncological process and the stage of the disease) for the purpose of evaluation, interpretation, and description of the results, the oncologist shall arrange for the referral of:

digital images obtained from pathomorphological examination results to the pathoanatomical bureau (department) of the fourth group (reference center) through information interaction, including via telemedicine technologies for remote interaction between medical workers;

digital images obtained from radiation imaging results to the remote diagnostic consultation center for radiation diagnostics through information interaction, including via telemedicine technologies for remote interaction between medical workers;

biopsy (surgical) material for repeated pathomorphological, immunohistochemical, and molecular genetic studies: to the pathoanatomical bureau (department) of the fourth group (reference center), as well as to molecular genetic laboratories for molecular genetic testing.

Treatment tactics are determined by a medical board (consilium) of physicians, including oncologists, a radiation oncologist, and a neurosurgeon (for nervous system tumors) of a medical organization that includes departments of surgical methods for the treatment of malignant neoplasms, systemic antineoplastic therapy, and radiation therapy (hereinafter referred to as the oncological consilium), including an oncological consilium conducted using telemedicine technologies, with the involvement of other specialist physicians if necessary.

Dispanserization (follow-up) by an oncologist for a patient with a diagnosed oncological disease is established and carried out in accordance with the procedure for follow-up of adults with oncological diseases.

For record-keeping purposes, information about a newly diagnosed case of an oncological disease shall be sent within 3 working days by the oncologist of the medical organization where the respective diagnosis was established to the oncological dispensary or the organization of the subject of the Russian Federation performing the function of registering patients with newly diagnosed malignant neoplasms, including via the Unified State Health Information System.

Specialized, including high-tech, medical care in medical organizations providing medical care to the adult population with oncological diseases is provided on the basis of medical indications stipulated by the regulations on the organization of specialized, including high-tech, medical care.

Specialized medical care, with the exception of high-tech medical care, in medical organizations subordinate to federal executive authorities is provided based on the medical indications provided for in paragraph 5 of the procedure for referring patients to medical organizations and other organizations subordinate to federal executive authorities for the provision of specialized (excluding high-tech) medical care, provided in the appendix to the provision on organizing the provision of specialized, including high-tech, medical care.

Waiting times for the provision of specialized (excluding high-tech) medical care must not exceed the timeframes established in the program of state guarantees of free medical care for citizens, approved by the Government of the Russian Federation.

If a patient with an oncological disease has medical indications for medical rehabilitation, the oncologist arranges for it to be provided in accordance with the procedure for organizing adult medical rehabilitation.

If a patient with an oncological disease has medical indications for sanatorium-resort treatment, the oncologist arranges for it in accordance with the procedure for organizing sanatorium-resort treatment.

Palliative medical care for a patient with oncological diseases is provided in accordance with the provision on organizing the provision of palliative medical care, including the procedure for interaction between medical organizations, social service organizations, public associations, and other non-profit organizations operating in the field of health protection.

If an oncological disease is suspected and/or detected in a patient during the provision of emergency medical care, the patient is transferred or referred to medical organizations providing medical care to patients with oncological diseases to determine management tactics and the need for additional other methods of specialized antitumor treatment.

Indications for hospitalization in a medical organization in an emergency or urgent form are:

1) the presence of complications of the oncological disease requiring the provision of specialized medical care in an emergency and urgent form;

2) presence of complications of treatment (surgical intervention, RT, drug therapy, etc.) of the oncological disease.

Indications for planned hospitalization in a medical organization are:

1) the need to perform complex interventional diagnostic medical procedures requiring subsequent monitoring in an inpatient or day-hospital setting;

2) the presence of indications for specialized antitumor treatment (surgical intervention, RT, including contact, EBRD and other types of RT, drug therapy, etc.) requiring monitoring in an inpatient or day hospital setting.

Indications for discharging a patient from a medical organization are:

1) completion of a course of treatment or one of the stages of providing specialized, including high-tech, medical care in an inpatient or day hospital setting, provided there are no treatment complications requiring drug correction and/or medical interventions in an inpatient setting;

2) refusal of the patient or their legal representative from specialized, including high-tech, medical care in an inpatient or day hospital setting established by the multidisciplinary team of the medical organization providing cancer care, provided there are no complications of the underlying disease and/or treatment requiring drug correction and/or medical interventions in an inpatient setting;

3) in cases of non-compliance by the patient with prescriptions or the internal regulations of the medical and prophylactic institution, provided this does not threaten the patient's life and the health of others;

4) the need to transfer the patient to another medical organization according to the relevant medical specialty profile.

The conclusion on the feasibility of transferring a patient to a specialized medical organization is made after a preliminary consultation based on the provided medical documents and/or a preliminary examination of the patient by specialist physicians of the medical organization to which the transfer is planned.

7. Additional Information

Factors influencing the prognosis of the disease include:

• size and extent of the primary tumor;

• depth of invasion of the primary tumor;

• tumor differentiation grade;

• presence/absence of perivascular, perilymphatic, perineural invasion;

• regional lymph node status (pN) (neck lymph node metastases halve patient survival)

• extranodal tumor extension;

• surgical resection margin status (R0-1);

• HPV status of the tumor.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Tatev A. Agababyan, Head of the Department of Diagnostic Radiology, A.F. Tsyb Medical Radiological Research Center — branch of the National Medical Research Radiological Center of the Russian Ministry of Health, PhD in Medicine, Obninsk https://orcid.org/0000-0002-9971-3451

2. Sevil B. Alieva, MD, PhD, Leading Researcher, Department of Radiation Oncology, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, member of the All-Russian Public Organization "Russian Society of Head and Neck Oncology Specialists".

3. Yuri V. Alymov, PhD in Medicine, Oncologist, Department of Surgical Treatment Methods No. 5 (Endocrine Oncology), N.N. Trapeznikov Institute of Clinical Oncology of the N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, Executive Director of the All-Russian Public Organization "Russian Society of Head and Neck Oncology Specialists"; ORCID: https://orcid.0000-0002-6851-9867

4. Anna S. Artemyeva, PhD in Medicine, Pathomorphologist, Head of the Scientific Laboratory of Tumor Morphology, N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health, Associate Professor at the Department of Additional Professional Education, N.N. Petrov National Medical Research Center of Oncology

5. Anna V. Boyko, MD, PhD, Professor, Head of the Department of Radiation Therapy with Modification, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center of the Russian Ministry of Health.

6. Mikhail V. Bolotin, PhD in Medicine, Researcher, Department of Surgical Treatment No. 11 for Upper Aerodigestive Tract Tumors, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, member of the All-Russian Public Organization "Russian Society of Head and Neck Oncology Specialists".

7. Larisa V. Bolotina, MD, PhD, Associate Professor of the Russian Academy of Sciences, Head of the Chemotherapy Department, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center of the Russian Ministry of Health. Chair of the Head and Neck Tumors Group of Practical Guidelines of the Russian Society of Clinical Oncology, Board Member.

8. Vyacheslav V. Vinogradov, MD, PhD, Professor, Head of the Scientific and Clinical Department of Otorhinolaryngological Oncology, Scientific and Clinical Center of Otorhinolaryngology of the Federal Medical-Biological Agency of Russia.

9. Lyubov Yu. Vladimirova, MD, PhD, Professor, Head of the Department of Drug Treatment of Tumors, National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation

10. Elena V. Gameeva, MD, PhD, Acting General Director, Federal Scientific and Clinical Center for Medical Rehabilitation and Balneology of the Federal Medical-Biological Agency of Russia

11. Artem R. Gevorkov, PhD in Medicine, Senior Researcher, Radiation Oncologist, Department of Radiation Therapy with Modification, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center of the Russian Ministry of Health, member of the All-Russian Public Organization "Russian Society of Head and Neck Oncology Specialists"

12. Mikhail M. Girshovich, PhD in Medicine, Radiation Oncologist, N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health; https://orcid.org/0000-0002-7925-9570

13. Igor A. Gulidov, Head of the Department of Radiation Therapy, A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center of the Russian Ministry of Health

14. Aleksandr O. Guz, PhD in Medicine, Oncologist, Head of the Department of Head and Neck Tumors, Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine

15. Nikolay A. Daikhes, Corresponding Member of the Russian Academy of Sciences, MD, PhD, Professor, Director of the Scientific and Clinical Center of Otorhinolaryngology of the Federal Medical-Biological Agency of Russia.

16. Ekaterina L. Dronova, Radiologist, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, member of the All-Russian Public Organization "Russian Society of Head and Neck Oncology Specialists".

17. Marina A. Engibaryan, MD, PhD, Head of the Department of Head and Neck Tumors, National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, member of the All-Russian Public Organization "Russian Society of Head and Neck Oncology Specialists".

18. Sergey A. Ivanov, MD, PhD, Professor of the Russian Academy of Sciences, Director of the A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center of the Russian Ministry of Health

19. Anastasia V. Ignatova, PhD in Medicine, Oncologist, Department of Surgical Treatment Methods No. 5, N.N. Trapeznikov Institute of Clinical Oncology of the N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, member of the All-Russian Public Organization "Russian Society of Head and Neck Oncology Specialists", Assistant at the Department of General and Clinical Dentistry, Peoples' Friendship University of Russia. ORCID: https://orcid.org/0000-0002-6796-0968

20. Veronika V. Klimenko, PhD in Medicine, Physician at the Clinical and Diagnostic Department, N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health; https://orcid.org/0000-0003-1079-4492

21. Anna L. Korniyetskaya, PhD in Medicine, Senior Researcher, Chemotherapy Department, Department of Drug Treatment of Tumors, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center of the Russian Ministry of Health.

22. Ekaterina V. Kostromina, PhD in Medicine, Ultrasound Diagnostics Physician, Radiologist at the Department of Diagnostic Radiology, Researcher at the Scientific Department of Diagnostic and Interventional Radiology, N.N. Petrov National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, Associate Professor at the Department of Radiology and Medical Imaging, Faculty of Postgraduate Education, Saint Petersburg State Medical University; https://orcid.0000-0002-4245-687X

23. Larisa A. Krasilnikova, PhD in Medicine, Cytopathologist N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health

24. Mikhail A. Kropotov, MD, PhD, Head of the Surgical Department No. 10 of Head and Neck Tumors, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health

25. Svetlana I. Kutukova, MD, PhD, Associate Professor, Academician I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Health of the Russian Federation, City Clinical Oncology Dispensary of Saint Petersburg

26. Denis E. Kulbakin, MD, PhD, Senior Researcher, Oncologist at the Department of Head and Neck Tumors, Cancer Research Institute of Tomsk National Research Medical Center

27. Aleksandr V. Mordovsky – PhD in Medicine, Researcher, Department of Head, Neck and Microsurgery, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center of the Russian Ministry of Health

28. Irina V. Novikova – PhD in Medicine, Senior Researcher, Department of Head, Neck and Microsurgery, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center of the Russian Ministry of Health

29. Ali M. Mudunov, MD, DSc, Professor of the Russian Academy of Sciences, Head of Surgical Treatment Department No. 10 for Head and Neck Tumors, National Medical Research Center for Oncology named after N.N. Blokhin of the Russian Ministry of Health, President of the All-Russian Public Organization "Russian Society of Head and Neck Oncology Specialists"

30. Shamil I. Musin, MD, PhD, Head of Surgical Department No. 6, Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Bashkortostan

31. Sergey O. Podvaznikov, MD, DSc, Professor, Russian Medical Academy of Continuous Professional Education of the Russian Ministry of Health, Vice-President of the All-Russian Public Organization "Russian Society of Head and Neck Oncology Specialists".

32. Aleksey A. Nevolskikh, MD, DSc, Deputy Director for Clinical Work, A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Center for Radiology of the Russian Ministry of Health.

33. Vyacheslav V. Polkin, MD, PhD, Head of the Department of Radiation and Surgical Treatment of Head and Neck Diseases, A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Center for Radiology of the Russian Ministry of Health

34. Polyakov Andrey Pavlovich, MD, PhD, Associate Professor, Head of the Department of Head, Neck and Microsurgery, P.A. Herzen Moscow Oncology Research Institute — branch of the National Medical Research Radiological Centre of the Russian Ministry of Health, member of the All-Russian Public Organization "Russian Society of Head and Neck Tumors"

35. Ponomareva Olga Igorevna, Radiologist, Department of Radiotherapy, N.N. Petrov National Medical Research Center of Oncology

36. Radzhabova Zamira Akhmed-Gadzhievna, MD, PhD, Associate Professor of the RAS, Head of the Department of Head and Neck Tumors, N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health, Associate Professor of the Department of Continuing Professional Education, N.N. Petrov National Medical Research Center of Oncology

37. Reshetov Igor Vladimirovich, MD, PhD, Academician of the RAS, Head of the Department of Oncology, Radiotherapy and Reconstructive Surgery, I.M. Sechenov First Moscow State Medical University, President of the All-Russian Public Organization "Federation of Specialists in the Treatment of Head and Neck Diseases"

38. Romanov Ilya Stanislavovich, MD, PhD, Senior Researcher, Department of Oncoendocrinology, N.N. Blokhin National Medical Research Center of Oncology, Associate Professor of the Department of Oncology, Faculty of Continuing Professional Education, Pirogov Russian National Research Medical University

39. Rubtsova Natalia Alevtinovna, MD, PhD, Head of the Department of Diagnostic Radiology, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health. Chief Freelance Specialist in Diagnostic and Instrumental Radiology of the Russian Ministry of Health in the Central Federal District of the Russian Federation.

40. Rudyk Andrey Nikolaevich, MD, PhD, Oncologist, Oncology Department No. 5 (Head and Neck Tumors), Professor M.Z. Sigal Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Tatarstan, Acting Head of the Department of Maxillofacial Surgery and Surgical Dentistry, Associate Professor of the Department of Oncology, Radiology and Palliative Medicine, Kazan State Medical Academy — branch of the Russian Medical Academy of Continuous Professional Education of the Russian Ministry of Health, Associate Professor of the Department of Surgical Diseases of Postgraduate Education, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan.

41. Semiglazova Tatiana Yuryevna, MD, PhD, Professor, Head of the Scientific Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health

42. Stepanova Alexandra Mikhailovna, Deputy General Director, Federal Scientific Clinical Center for Medical Rehabilitation and Balneology of the Federal Medical-Biological Agency (FMBA of Russia)

43. Sukortseva Natalia Sergeevna, Assistant at the Department of Oncology, Reconstructive Surgery and Radiotherapy, Oncologist at University Clinical Hospital No. 1 of Sechenov University

44. Elena V. Tkachenko, MD, PhD, Head of the Short-Term Antitumor Drug Therapy Department, Researcher at the Scientific Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, National Medical Research Center for Oncology named after N.N. Petrov of the Russian Ministry of Health, https://orcid.org/0000-0001-6375-8335

45. Falaleeva Natalia Alexandrovna, Head of the Department of Drug Treatment of Malignant Neoplasms, A.F. Tsyb Medical Radiological Research Centre — branch of the National Medical Research Radiological Centre of the Russian Ministry of Health

46. Fedenko Alexander Alexandrovich, MD, PhD, Professor of the RAS, Head of the Department of Drug Treatment of Tumors, P.A. Herzen Moscow Oncology Research Institute — branch of the National Medical Research Radiological Centre of the Russian Ministry of Health

47. Evgeny V. Khmelevsky, MD, PhD, Professor, Head of the Department of Radiation Therapy, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health, radiation oncologist at the P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health.

48. Khodjibekova Malika Maratovna, MD, PhD, Radiologist at the Department of Radionuclide Diagnostics, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health.

49. Tsirlina Evgenia Vladimirovna, MD, PhD, Endocrinologist, Department of Functional Diagnostics, N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health

50. Choinzonov Evgeny Lhamatsyrenovich, MD, DSc, Academician of the RAS, Director of the Cancer Research Institute, Tomsk National Research Medical Center; Head of the Department of Head and Neck Tumors, Cancer Research Institute, Tomsk National Research Medical Center; Head of the Department of Oncology, Siberian State Medical University of the Russian Ministry of Health; Member of the All-Russian Public Organization "Russian Society of Head and Neck Tumors Specialists"

51. Yakovleva Lilia Pavlovna, PhD, Oncologist, Head of the Center for Diagnostics and Treatment of Head and Neck Tumors, Loginov Moscow Clinical Scientific Center of the Ministry of Health of the Russian Federation

No conflict of interest

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

• oncologists;

• surgeons;

• radiologists;

• medical geneticists;

• medical students, residents, and graduate students.

Methods used for evidence collection/selection: search in electronic databases; analysis of current scientific developments on oropharyngeal cancer in Russia and abroad; synthesis of practical experience of Russian and foreign specialists.

Table 2. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table 3. Scale for assessing levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 4. Scale for assessing grades of recommendation (GR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines

The mechanism for updating clinical guidelines provides for their systematic revision at least once every 3 years, as well as upon the emergence of new data from the standpoint of evidence-based medicine regarding the diagnosis, treatment, and prevention of rehabilitation for specific diseases, or in the presence of justified additions/comments to previously approved Clinical Guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

Reference materials are not provided.

Appendix B. Physician Action Algorithms

Flowchart of diagnosis and treatment of a patient with oropharyngeal cancer

Management algorithm for a patient with suspected oropharyngeal cancer

Appendix C. Patient Information

Guidelines for post-treatment follow-up

Follow-up after completed treatment is essential for maintaining the patient's health. Typically, during the 1st year, consultations with an oncologist are recommended every 1–3 months, in the 2nd year every 2–6 months, and at 3–5 years every 4–8 months. After 5 years from surgery, visits are conducted annually or upon the appearance of symptoms. Nevertheless, the frequency of visits may be increased depending on the disease characteristics and associated risks, and is discussed individually in each specific case. If complaints arise or symptoms present before treatment recur, it is necessary to consult a doctor immediately without waiting for the scheduled visit.

The purpose of these visits is to monitor not only the oncological disease, but also side effects, including delayed ones (e.g., hypothyroidism after neck radiation therapy, nutritional status decline, assessment of speech and swallowing functions, etc.).

Recommendations regarding lifestyle and nutrition should be individualized taking into account the extent of treatment received, the risks and severity of complications, and the patient's characteristics.

Benefits of quitting smoking and alcohol consumption:

• higher survival rates;

• greater treatment efficacy;

• fewer and less severe side effects of anticancer treatment (cardiopulmonary complications, fatigue, weight loss, mucositis, loss of taste);

• faster recovery of general condition after treatment;

• lower risk of recurrence;

• lower risk of secondary tumors;

• lower risk of infections;

• higher quality of life.

1. If body temperature rises to 38 °C or higher:

• start antibiotic therapy as prescribed by the oncologist (chemotherapy specialist).

2. In case of stomatitis:

• diet with mechanical and thermal sparing of the mucosa;

• frequent mouth rinsing (every hour) with chamomile, oak bark, or sage decoctions, lubricate the oral cavity with sea buckthorn (peach) oil;

• treat the oral cavity as prescribed by the oncologist (chemotherapy specialist).

3. In case of diarrhea:

• diet: exclude fatty, spicy, smoked, sweet, dairy, and high-fiber foods. Lean meat, flour products, fermented milk products, and rice water are permitted. Drink plenty of fluids;

• take medications as prescribed by a clinical oncologist (chemotherapy specialist).

4. For nausea:

• take medications as prescribed by a clinical oncologist (chemotherapy specialist).

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. WHO/ECOG Performance Status Scale

Russian title: WHO Patient Performance Status Scale/ECOG

Original title: The Eastern Cooperative Oncology Group/World Health Organization Performance Status (ECOG/WHO PS)

Source (official developer website, validated publication): https://ecog-acrin.org/resources/ecog-performance-status

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP: Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982, 5(6):649-655

Type: rating scale

Purpose: to describe the patient's level of functioning in terms of their ability to care for themselves, daily activities, and physical abilities (walking, work, etc.).

Contents:

Key (interpretation): provided within the scale itself

Appendix G2. Questionnaire for initial patient presentation to a primary care physician within the framework of cancer awareness

Russian title: Questionnaire for initial patient presentation to a primary care physician within the framework of cancer awareness

Original title (if applicable): none

Source (official developer website, validation publication): https://oncology-association.ru/

Type (underline): questionnaire

Purpose: assessment of the probability of malignant neoplasms in a patient

Assessment tool, content:

Questionnaire for initial patient presentation to a primary care physician within the framework of cancer awareness (select correct answers, underline as appropriate, fill in if necessary)

Date of completion:

Full name:

1. Do you have occupational hazards at work?

1. No

2. Yes

2. How many years do you work / have you worked with occupational hazards?

1. Up to 1 year

2. Up to 3 years

3. From 3 to 5 years

4. 6–10 years

5. More than 10 years

6. More than 15 years

3. Have any of your close relatives had or do they have cancer of the ENT organs?

1. No

2. Has had or has

3. I don't know

4. Do you smoke (or have you smoked)?

1. No

2. Yes

3. More than 20 cigarettes per day

4. Smoking history less than 10 years

5. Smoking history 10–15 years

6. Smoking history more than 20 years

5. Have you noticed any weight loss recently?

1. No

2. I don't know

3. Yes, by more than 5 kg

4. Yes, I was on a diet

5. Are you bothered by increased weakness and fatigue that is disproportionate to exertion?

1. No

2. More than 1 month

3. More than 6 months

7. Are you troubled by excessive generalized sweating, possibly worsening at night?

1. No

2. Yes, it appeared within the last 6–12 months

3. Always been present

8. Do you have pallor or skin discoloration?

1. No

2. Yes

3. I don't know

9. Have you recently noticed enlarged lymph nodes or other lumps in your neck?

1. No

2. Yes, painless

3. Yes, painful

10. Do you have any skin growths or long-standing non-healing ulcers on your face, scalp, or neck?

1. No

2. Yes

3. If yes, specify what exactly? (type your own answer)

11. Have you recently noticed facial deformity due to newly appeared masses or swelling (changes in the shape of the nose, eyes, etc.)?

1. No

2. Yes

3. If yes, specify what exactly? (type your own answer)

12. Are you troubled by a prolonged cough or throat clearing?

1. No

2. Yes

3. With sputum

4. Blood-tinged

13. Are you bothered by hoarseness?

1. No

2. Periodically

3. Constantly over the last month

4. Yes, not evaluated and not treated

5. Yes, treatment received was ineffective

14. Are you troubled by difficulty breathing through the natural airways?

1. No

2. Sometimes

3. Frequently

4. Difficulty breathing is present at rest

5. With minor physical exertion

6. With significant physical exertion

15. Are you troubled by a "lump or foreign body sensation" in your throat?

1. No

2. Sometimes

3. Frequently or constantly

16. Are you troubled by an unpleasant taste in your mouth and/or bad breath?

1. No

2. Sometimes

3. Frequently or constantly

17. Are you troubled by difficulty swallowing food?

1. No

2. Yes, only liquids

3. Yes, only solid food

4. Swallowing is painful

5. Choking and coughing occur while eating

6. Within the last month

7. More than 3 months

18. Are you troubled by difficulty breathing through your nose?

1. No

2. Rarely

3. Frequently (constantly)

4. Nasal breathing difficulty on both sides

5. Nasal breathing difficulty on the right/left

6. Nasal breathing absent on both sides

7. Nasal breathing absent on the right/left

19. Rate your sense of smell:

1. Normal

2. Decreased

3. Absent

4. Bilaterally

5. Right/left

20. Do you experience nasal discharge and/or post-nasal drip?

1. No

2. Rarely

3. Frequently (constantly)

4. Mucous or clear

5. Purulent with an unpleasant odor

6. Blood-tinged

21. Do you feel discomfort or pain in the facial area corresponding to the paranasal sinuses?

1. No

2. Rarely

3. Frequently (constantly)

22. Have you recently noticed any new growth in the nasal cavity or throat?

1. No

2. Yes

3. Painless

4. Painful

5. Bleeding

Key (interpretation): Affirmative answers to questions 1 through 8, in the presence of symptoms described in questions 9 through 23, suggest a possible tumor disease; in such cases, a detailed examination by relevant specialists is required.

Appendix G3. NRS 2002 SCALE

Russian title: NRS-2002 scale for nutritional risk screening.

Original title: NRS-2002.

Source (official developer website, validation publication):

Kondrup J., Allison S.P., Elia M., Vellas B., Plauth M. Educational and Clinical Practice Committee, European Society of Parenteral and Enteral Nutrition (ESPEN). ESPEN Guidelines for Nutrition Screening 2002 Clinical Nutrition (2003) 22(4): 415 - 421.

Type: rating scale

Purpose: The European Society for Clinical Nutrition and Metabolism (ESPEN) recommends using the two-step NRS-2002 scale for nutritional risk screening.

Content:

Final screening

Notes:

1. Patient age 70 years or older — add 1 point to the total score.

2. More than 3 points — high risk of malnutrition, requiring the development of a nutritional support program.

3. Less than 3 points — rescreening every week. If surgical treatment is planned, a preoperative preparation program is required.

Notes: none.

Appendix G4. Malnutrition Universal Screening Tool (MUST)

Russian title: Universal malnutrition screening tool

Original title (if applicable): Malnutrition Universal Screening Tool, MUST

Source (official developer website, validation publication): Stratton R.J., Hackston A., Longmore D., et al. (2004) Malnutrition in hospital outpatients and inpatients: prevalence, concurrent validity and ease of use of the "malnutrition universal screening tool" ("MUST") for adults. Br J Nutr 92, 799 - 808

Type: scale

Purpose: Screening for malnutrition in elderly and senile patients

Content (template):

Total score: ___________/30

Interpretation of results (full scale from A to T):

>23.5 points — normal nutritional status

17–23.5 points — risk of malnutrition

<17 points — malnutrition.