Patients With Head and Neck Cancer Require Double-Testing for Accurate Prognosis

Oropharyngeal cancer is frequently associated with HPV, specifically strains 16 and 18, so patients with oropharyngeal cancer (a type of head and neck cancer in the middle of the throat) are routinely tested for HPV.

However, the current standard testing for HPV in tumors is to test for the protein P16 (a common biomarker for HPV) instead of testing for the literal virus.

A recent study published in The Lancet Oncology found not all patients who tested positive for P16 tested positive for HPV, and vice versa. Patients who tested positive for both the biomarker protein and the virus had significantly better five-year survival rates than patients with “discordant” test results, where they were positive for one and not the other.

“Routine HPV testing alongside p16 evaluation, or at least following a positive result on p16 immunohistochemistry, should be mandated in oropharyngeal cancer clinical trials. It is also recommended in the clinical setting for more accurate counselling on prognosis, and in future circumstances in which treatment de-escalation or intensification are being considered,” the study authors concluded.

The study evaluated the data from 13 other international studies and a total of 7,654 patients. A total of 76.5% (5,885 patients) were active or former smokers, a key risk factor for oropharyngeal cancer. The vast majority (78.8%) had locally advanced disease, or stage 3 or 4.

Double-tested patients revealed 46.5% (3,560 patients) were negative for both P16 and HPV and 44.3% (3,390) were positive for the protein and the virus. Of those with discordant test results, 3.8% (289) were positive for HPV but not P16 and 5.4% (415) were negative for HPV while testing positive for the P16 biomarker.

Of note, North American patients were the highest proportion of patients who were HPV-positive but P16-negative (18 of 51 patients from this region).

Other notable differences in patient groups include age, disease stage and drinking and smoking habits. Patients with positive P16 and HPV results were younger, and double-negative patients more often presented with an earlier disease stage. Patients who did not smoke or drink were more likely to be double positive while those that had smoked and drank were more likely to be double negative.

Double-negative patients were also more likely to be treated with surgeries and palliative care than double-positive patients.

Patients with discordant test results saw “significantly lower overall survival and disease-free survival” regardless of which test was positive compared to patients who were positive for both HPV and P16.

The difference in positive status for discordant patients was significant when paired with smoking history. Patients P16 positive and HPV negative who smoked had a much worse prognosis than double-positive smokers but were not significantly different than smokers who were negative for P16 and HPV positive or double-negative smokers.

These data may prove important for treatment decisions in the oropharyngeal patient population and may lead to changes for the HPV testing standards in clinical trials and standard care when evaluating prognosis and treatment decisions.

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