Responding to alarming trends in head and neck cancers associated with the human papillomavirus (HPV), the College of American Pathologists (CAP) has issued a guideline that recommends testing practices to ensure accurate and consistent HPV diagnosis. “Accurate HPV assessment in head and neck cancers is becoming critical,” said guideline co-chair William C. Faquin, MD, PhD, FCAP, a pathologist at Massachusetts General Hospital, Boston, in a statement. “It is also important to know when testing is not indicated, and this new guideline provides that guidance.”

The National Cancer Institute reports that high-risk HPV causes about 70% of cancers of the oropharynx. HPV head and neck cancers have been on the rise, particularly in middle-aged Caucasian men. Why the disease is so prevalent in this specific demographic group is unknown, project co-chair, James S. Lewis Jr., MD, FCAP, professor of pathology, microbiology, and immunology at Vanderbilt University Medical Center in Nashville, Tennessee, told CLN Stat. “We think there are both behavioral/social factors as well as genetic ones. This is still being defined,” Lewis said. Smoking is another underrecognized risk factor for this type of cancer.

The disease causes few symptoms at the primary site, increasing the likelihood of the cancer spreading to lymph nodes before being detected. One of the most practical aspects of this guidance is a testing algorithm for high-risk HPV (HR-HPV), which outlines the steps/recommendations for addressing a patient specimen in routine clinical practice. “It covers any head and neck squamous cell carcinoma, presenting as a primary lesion or in neck lymph nodes, and methodically takes the pathologist through exactly what we recommend to do (or not to do),” Lewis explained. “We believe [the algorithm] will be the best instrument to help assure consistent practice out there,” he added.

The guideline authors called for HR-HPV tests in all patients newly diagnosed with HPV–positive oropharyngeal squamous cell carcinoma (SCC). This includes all histologic subtypes. Testing can be performed on the primary tumor or on a regional lymph node metastasis, if the clinical findings are consistent with an oropharyngeal primary. This was a strong recommendation, based specifically on how the data is actually used in clinical practice, Lewis said.

The document also recommends routine HR-HPV testing in patients with metastatic SCC of unknown primary in a cervical upper or mid jugular chain (level II or III) lymph node. “An explanatory note on the significance of a positive HPV result is recommended,” the authors suggested.

Given the link between marked overexpression of the tumor suppressor protein p16 and the presence of transcriptionally active HR-HPV, the authors recommended testing oropharyngeal tissue specimens for p16 via immunohistochemistry (IHC), as a surrogate marker for HR-HPV.

There are instances when clinical lab professionals should hold off from routine testing HR-HPV testing. As an example, such testing is not suitable for patients with nonsquamous carcinomas of the oropharynx or nonoropharyngeal primary tumors of the head and neck. Similarly, low-risk HPV testing should not be performed on patients with head and neck carcinomas.

The hope is that these guidelines will encourage testing in all oropharyngeal SCC patients across all practice settings and that it will be done in the same manner, Lewis said. Another goal is to get people to stop testing nonoropharyngeal carcinoma specimens. “It’s a great start,” he said, “but is only the start of the process. We will revisit these guidelines in the coming years and expect that they will change as HR-HPV testing modalities and clinical practice change.”