HPV-mediated (p16-positive) oropharyngeal cancer (staging)

Human papillomavirus (HPV)-mediated oropharyngeal (p16+) cancer staging refers to TNM staging of squamous cell carcinomas of the oropharynx that test positive for p16, an immunohistochemical proxy for HPV infection. Nodal metastases of p16+ squamous cell carcinoma without an identified primary tumour are also staged under this system. This classification is new in the 8^th edition of the classification by the American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC), published in 2017 ^1-4.

Primary tumour (T)

• T0: no primary identified

• T1: tumour ≤2 cm in greatest dimension

• T2: tumour >2 cm and ≤4 cm

• T3

  • tumour >4 cm, or

  • tumour extension to lingual surface of epiglottis

• T4: moderately advanced local disease in which tumour invades any of the following or beyond*:

  • larynx (except lingual surface of epiglottis)

  • extrinsic muscles of the tongue** 

  • medial pterygoid muscle

  • hard palate

  • mandible

*Note: The UICC also lists additional T4 criteria that the AJCC does not: encasement of carotid artery or invasion of lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base (identical to the T4b criteria in p16-negative oropharyngeal cancer staging).

**Note: According to the AJCC, involvement of the palatoglossus muscle within the oropharynx does not change the T category and this criterion mainly denotes invasion "anteriorly to the extrinsic muscles of the tongue in the floor of the mouth" ¹. According to the UICC, this criterion is defined as "deep/extrinsic muscle of tongue (genioglossus, hyoglossus, palatoglossus, and styloglossus)" ⁴. The application of this criterion is controversial because only the genioglossus is deep among the extrinsic tongue muscles ⁵.

Regional lymph node (N)

Clinical (cN) criteria

Clinical criteria apply to all patients before surgical treatment, by using information from physical examination, imaging, and/or needle biopsies.

• NX: regional lymph nodes cannot be assessed

• cN0: no regional lymph node metastasis

• cN1: one or more ipsilateral lymph nodes, all ≤6 cm

• cN2: contralateral or bilateral lymph nodes, all ≤6 cm

• cN3: lymph node(s) >6 cm

Pathological (pN) criteria

Pathological criteria apply only to patients treated with surgery who thus have many specimens available for histopathologic examination.

• NX: regional lymph nodes cannot be assessed

• pN0: no regional lymph node metastasis

• pN1: metastasis in ≤4 lymph nodes

• pN2: metastasis in >4 lymph nodes

Distant metastases (M)

The terms pM0 and MX are not valid TNM categories. The following categories may be used:

• cM0: no evidence of metastases

• cM1: distant metastasis

• pM1: distant metastasis, microscopically confirmed

Stage groups

Clinical (cTNM)

• stage I

  • [T0, T1, T2], [N0, N1], M0

• stage II

  • [T0, T1, T2], N2, M0

  • T3, [N0, N1, N2], M0

• stage III

  • [T0, T1, T2, T3, T4], N3, M0

  • T4, [N0, N1, N2, N3]

• stage IV

  • [Any T], [Any N], M1

Pathological (pTNM)

• stage I

  • [T0, T1, T2], [N0, N1], M0

• stage II

  • [T0, T1, T2], N2, M0

  • [T3 or T4], [N0, N1], M0

• stage III

  • [T3, T4], N2, M0

• ​​stage IV

  • [Any T], [Any N], M1

Both clinical and pathological distant metastasis assessments (cM0, cM1, or pM1) can be used for pTNM stage grouping.

See also

• non-HPV-mediated oropharyngeal (p16-negative) cancer staging

• WHO classification of head and neck tumours

• cervical lymph node staging

• cervical lymph node levels