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HPV and p16 Testing in Oropharyngeal Squamous Cell Carcinoma

Methodology, Interpretation, and Significance



Beyond Hot Topic is an opportunity for viewers to submit questions to the Hot Topic presenter. The opportunity to submit questions for this topic is now closed.

The following questions were submitted by viewers and answered by the presenter, Joaquín García, MD, Assistant Professor of Laboratory Med/Pathology, College of Medicine at Mayo Clinic in Rochester, Minnesota. 

Questions are presented as submitted (unedited).

  1. How is "not strong and diffuse" p16 immunostaining interpreted and handled (eg, diffuse weak to moderate staining or patchy strong staining)?

    Current head and neck pathology literature supports designating a case of oropharyngeal squamous cell carcinoma (OPSCC) as p16 positive if at least 70% of tumor cells show strong immunoreactivity. Actually, the vast majority of p16-positive cases show staining in >90% of tumor cells, making the designation rather straightforward. It is important to recognize that p16 immunoreactivity is not exclusive to OPSCC but can be seen in other head and neck epithelial malignancies—these tumors are more likely to exhibit focal and weak staining patterns. I would, therefore, suggest using caution in calling a tumor p16 positive if <70% of tumor cells show strong nuclear and cytoplasmic staining. In fact, I would be inclined to repeat the stain, or interpret it as negative or equivocal rather than signing it out as p16 positive.

  2. Which HPV methodology does Mayo Clinic use routinely for testing a newly diagnosed oropharyngeal squamous cell carcinoma?

    At Mayo Clinic Rochester, we test all newly diagnosed cases of OPSCC for p16 expression using immunohistochemistry and high-risk HPV infection by in situ hybridization. We typically perform these studies on resection rather than biopsy specimens.

  3. Is frozen or fresh tissue useful for HPV typing or is FFPE the gold standard?

    Fortunately, p16 immunohistochemistry and HPV in situ hybridization testing on formalin-fixed, paraffin-embedded (FFPE) tissue is currently considered the gold standard in clinical settings (ie, surgical pathology material).

  4. Do you also perform HPV or p16 testing for laryngeal and pharyngeal cancers?

    In the head and neck, we do not feel there is sufficient scientific evidence currently to support reflexive p16 immunohistochemistry and HPV in situ hybridization testing in anatomic sites other than the oropharynx (tonsil and base of tongue).

  5. Is there any role for screening for oral cancers with HPV screening?

    This is a major topic of discussion within the head and neck oncology community. Currently, there is no screening tool that is considered "ready for prime time," but this may change in coming years. One major obstacle for designing HPV screening tools in this context is that HPV can be identified in normal, benign, and malignant squamous epithelium, as well as nonsquamous lesions.

  6. Does Dr. García have a recommendation for HPV/p16 testing in OPSSC in general community practice?

    I would encourage community pathology practices to at least perform p16 immunohistochemistry on newly diagnosed cases of OPSCC. Given that the majority of p16-positive cases of OPSCC are also HPV positive, and only a fraction of p16-negative cases are HPV positive, some argue that p16 testing alone is sufficient. However, if high-risk HPV in situ hybridization testing is available, I would suggest performing this routinely as well if requested by clinical colleagues. In our practice at Mayo Clinic Rochester, members of the head and neck oncology community prefer to have both p16 and HPV testing performed.

  7. What about HPV testing as a screening tool for OPSCC? Currently there are no FDA-approved methodologies for this, yet OPSCC is on the rise.

    This is a major topic of discussion within the head and neck oncology community. Currently, there is no screening tool that is considered "ready for prime time," but this may change in coming years. One major obstacle for designing HPV screening tools in this context is that HPV can be identified in normal, benign, and malignant squamous epithelium, as well as nonsquamous lesions.


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