Human Papillomavirus Testing in Head and Neck Carcinomas: ASCO Clinical Practice Guideline Endorsement of the College of American Pathologists Guideline

Abstract

Purpose The College of American Pathologists produced an evidence-based guideline on testing, application, interpretation, and reporting of human papillomavirus (HPV) and surrogate marker tests in head and neck carcinomas that was determined to be relevant to the American Society of Clinical Oncology (ASCO) membership. Methods The College of American Pathologists HPV Testing in Head and Neck Carcinomas guideline was reviewed by ASCO content experts for clinical accuracy and by methodologists for developmental rigor. On favorable review, an ASCO Expert Panel was convened to review the guideline contents and recommendations. Results The ASCO Expert Panel determined that the recommendations from the HPV Testing in Head and Neck Carcinomas guideline, published in 2018, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the guideline and added minor qualifying statements. Recommendations It is recommended that HPV tumor status should be determined for newly diagnosed oropharyngeal squamous cell carcinomas. HPV tumor status testing may be performed by surrogate marker p16 immunohistochemistry either on the primary tumor or from cervical nodal metastases only if an oropharyngeal primary tumor is present. The threshold for positivity is at least 70% nuclear and cytoplasmic expression with at least moderate to strong intensity. Additional confirmatory testing may be done at the discretion of the pathologist and/or treating clinician. Pathologists should not routinely determine HPV tumor status in nonsquamous carcinomas of the oropharynx or non–oropharyngeal squamous cell carcinomas of the head and neck. When there is uncertainty of histologic type or whether a poorly differentiated oropharyngeal tumor is nonsquamous, HPV tumor status testing may be warranted and at the discretion of the pathologist and/or treating clinician. Additional information is available at: www.asco.org/head-neck-cancer-guidelines .

Vulval squamous cell carcinoma and its precursors

“…in a lymph node biopsy showing only metastatic carcinoma, or a core biopsy specimen), the criteria for interpretation of p16 staining are less clear; we suggest using a cut‐off for abnormal staining of moderate to intense nuclear and cytoplasmic staining of >70% of tumour cells (i.e. the criteria used to interpret p16 immunostaining in head and neck squamous cell carcinomas according to American Society of Clinical Oncology/College of American Pathologists guidelines) . Anecdotally, this cut‐off appears to work well in our experience, with all or almost all tumour cells staining positively for p16 if foci of keratinisation are excluded from consideration.…”

Heterogeneity of p16 immunohistochemistry and increased sensitivity of RNA in situ hybridization in cytology specimens of HPV‐related head and neck squamous cell carcinoma

“…Although patients with HPV‐HNSCC frequently present with lymph node metastases, their prognosis is favorable compared with that of patients with conventional HNSCC, with an improved response to chemoradiation . Given the prognostic implications of HPV status in HNSCC, it is recommended that HPV testing be performed on all newly diagnosed SCCs from patients with suspected oropharyngeal primary tumors . In addition to oropharyngeal primary tumors, tumors of an unknown primary that are metastatic to level II or III lymph nodes (or an unknown cervical lymph node level) also should be tested for HPV …”

“…Given the prognostic implications of HPV status in HNSCC, it is recommended that HPV testing be performed on all newly diagnosed SCCs from patients with suspected oropharyngeal primary tumors . In addition to oropharyngeal primary tumors, tumors of an unknown primary that are metastatic to level II or III lymph nodes (or an unknown cervical lymph node level) also should be tested for HPV …”

“…As such, p16 overexpression as determined by IHC has become a widely used and reliable surrogate for HPV status in patients with oropharyngeal HNSCC . Recently, guidelines for HPV testing in patients with HNSCC were released by the College of American Pathologists (CAP) and subsequently endorsed by the American Society of Clinical Oncology . As per the CAP guidelines for testing surgical specimens, p16 IHC may be used as the sole marker for HPV when testing an oropharyngeal primary tumor, and additional HPV‐specific studies can be performed at the discretion of the pathologist or clinician.…”

Mutation of chromatin regulators and focal hotspot alterations characterize human papillomavirus–positive oropharyngeal squamous cell carcinoma

“…The pathology of the primary tumors was confirmed by 2 independent pathologists, and tumor tissue was microdissected to yield at least 80% tumor purity. Tumors were considered HPV+ if they were positive on p16 immunohistochemistry or if they were positive on in situ hybridization for high‐risk subtypes in accordance with the recent College of American Pathologists guidelines on HPV testing . In equivocal cases, HPV‐16 E6 and E7 viral oncoproteins were detected via polymerase chain reaction for confirmation (Supporting Table 1).…”