Human Papillomavirus Testing in Head and Neck Carcinomas

Over the past few decades, our understanding of HPV’s role in certain head and neck cancers, particularly those in the oropharynx, has increased. Patients with high-risk (HR) HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) have a better prognosis and may be candidates for less aggressive treatments. Consequently, accurate assessment of tumor HPV status is critical.

HPV 16 is the most common HR-HPV type associated with OPSCC, but a significant minority (10%-12%) of OPSCC cases can be associated with other HR-HPV types including 18, 31, 33, etc, with as many as 18 different types which should be covered in any HPV-specific test that is utilized. Based on large studies across many different countries worldwide, HR-HPV ISH or PCR should include at least types 16, 18, 26, 33, 35, and 58.

Recommendation 1 – Pathologists should perform HR-HPV testing on all patients with newly diagnosed OPSCC, including all histologic subtypes. This testing may be performed on the primary tumor or on a regional lymph node metastasis when the clinical findings are consistent with an oropharyngeal primary.

More than 100 studies identified in the systematic review of the literature from just the past 4 years informed this recommendation.

Because of the abundant literature on p16 IHC as an independent predictor of improved patient prognosis and based on its widespread availability, ease of use, reproducibility of interpretation, low cost, and excellent performance on small specimen samples, the expert panel concluded that pathologists should perform HR-HPV testing by surrogate marker p16 IHC on oropharyngeal tissue specimens (ie, non-cytology) or on cervical nodal metastases (also non-cytology) when a mass lesion is clinically or radiographically identified in the oropharynx. Additional HPV-specific testing should be performed in several different “caveat” scenarios, most importantly when morphology does not match p16 results and in low attributable fraction (<50%) geographic areas. HPV-specific testing may also be done at the discretion of the pathologist, treating clinician, or in the context of a clinical trial. Further, there are scenario-specific recommendations from the expert panel for the use of HPV-specific testing in distant metastasis tumor specimens.

As with any clinical, evidence-based guideline, specifically following the recommendations is not mandatory. Recommendations may be incorporated into future versions of the CAP Laboratory Accreditation Programs (LAP) checklists; however, they are not currently required by LAP or any regulatory or accrediting agency. It is only highly encouraged that laboratories adopt these recommendations. The hope is that over time, laboratories and clinicians will follow the guideline recommendations.

Pathologists should routinely perform HR-HPV testing on newly diagnosed sinonasal SCC.HPV-specific testing is recommended, but performing p16 immunohistochemistry followed by HPV-specific testing for p16 positive tumors is acceptable. Pathologists should not routinely perform HR-HPV testing on other non-OPSCCs (larynx, oral cavity, nasopharynx, hypopharynx) nor on non-squamous carcinomas of the oropharynx. Routine HR-HPV testing in non-OPSCCs is not indicated because there is insufficient evidence to support prognostic or therapeutic differences based on the presence or absence of HR-HPV. Additionally, there was insufficient evidence to support HR-HPV testing on non-squamous carcinomas of the oropharynx. While HR-HPV testing can be performed on a select, case-by-case basis, routine testing is not recommended.