Human Papillomavirus Testing in Head and Neck Carcinomas Endorsement Guideline

An interview with Dr. Carole Fakhry from Johns Hopkins School of Medicine on the ASCO endorsement of the CAP guideline on human papillomavirus (HPV) testing in head and neck carcinomas. Read the full guideline at www.asco.org/head-neck-cancer-guidelines

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Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Carole Fakhry from Johns Hopkins School of Medicine, lead author on Human Papillomavirus Testing in Head and Neck Carcinomas: ASCO Clinical Practice Guideline Endorsement of the CAP Guideline. Thank you for being here today, Dr. Fakhry.

Thanks for having me.

So first, can you give us a general overview of what this guideline covers?

Sure. This guideline serves to guide multi-disciplinary clinicians in the evaluation of head and neck cancers. And it really starts to clarify which HPV tests to order and when. Also discusses some of the imitations of using surrogate HPV testing in specific situations.

The College of American Pathology Guidelines were recently published and we are providing an endorsement with certain classifications and discussions of nuances that we as a committee felt were important and clinically significant, specifically, aspects that could alter clinical care.

So what are the key recommendations of this guideline?

So first and foremost, the key recommendation is that HPV tumor detection should be performed in oropharynx tumors and not for non-oropharynx tumors. An important aspect of that is that HPV tumor testing should not be altered based on sex, race, age, or smoking history. Another important recommendation is that the term "high-risk" only be used when HPV-specific testing is performed.

That would establish the tumor is ideologically related to the infection human papillomavirus. In the absence of HPV-specific testing, we recommend that the term HPV-related tumors be used, and that p16 deserving for oropharynx tumors only.

And can you tell us a little bit about the qualifying statements made on some of these recommendations, and why the expert panel decided to include these?

Sure. So one of the qualifying statements that we did make was a generalized one, and the one that I kind of just touched upon, that the term "high-risk HPV" should only be used in situations when HPV-specific testing was performed. And that's because sometimes things are p16 positive but not necessarily HPV-related or etiologically related to the infections.

So as a committee, we wanted to make sure that that was clear. In light of that, one of the recommendations from the CAP Guidelines was that for tissue specimens presenting with medistatic squamma cell carcinoma of unknown primary and cervical upper, or mid-jugular, chain lymph nodes, pathologists should perform p16 in situ hybridisation.

They also had added a note saying that additional high-risk HPV testing on p16-positive cases should be performed for tumors located outside of level two or three in the neck, and/or for tumors with keratinizing morphology. So in the qualifying statement, our committee felt that p16 immunohistochemistry alone was not sufficient in the scenario of an unknown primary cancer.

We can get false positives and tumors that are p16-positive but not related to HPV. Can arise in situations of metastasis from the skin cancers, salivary gland malignancies, or even lung primaries. Therefore, in the case of an unknown primary, we would recommend HPV-specific testing. What other important consideration that our committee felt was important to clarify was that in the unknown primary, whether or not a tumor is felt to have keratinizing or non-keratinizing morphology, that HPV-specific testing should be done.

And the reason for that is that the pathologists acknowledge that considering a tumor keratinizing or non-keratinizing may be a difficult distinction for most pathologists, and that discerning HPV status may actually be easier and may help hone in on the diagnosis. And as part of this, what we did was we created an algorithm which simplified the College of American Pathologists algorithm for HPV detection. So there are fewer nodes in terms of HPV detection.

And in general, for oropharynx tumors, we recommend starting a p16 immunohistochemistry. We endorse the 70% cutoff used on immunohistochemistry for p16. And if it's an oropharynx tumor with greater than 70% p16 staining, then that can be considered an HPV-related squama cell carcinoma. For non-oropharynx tumors, we don't ever recommend HPV tumor status evaluation. And then for unknown primary, whether or not it's a level 2 or 3, starting with p16 is adequate, but if it is p16-positive, that needs to be followed up with HPV-specific testing to be deemed HPV-related.

In the College of American Pathology algorithm, acknowledging that determining HPV status can be complex, there are more nodes and more decisions that could be made in terms of discerning what's HPV-related and what's not. And so our committee tried to distill it down and simplify the algorithm.

And finally, how will these guideline recommendations affect patients?

So it is recommended that patients with oropharynx cancer be tested for HPV. And so this really helps their clinicians determine how to best test their tumors. In cases that are not so clear that are not oropharynx tumors, it also helps to guide their clinicians in terms of the when and how to test their tumors.

Great. Thank you for your work on this important guideline, and thank you for your time today, Dr. Fakhry.

Thanks for having me.

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