Vaccination against human papillomavirus (HPV) reduces the prevalence of oral infection by an estimated 88% among young adults in the United States, a protection that could help reduce rates of HPV-related oropharyngeal cancers, according to data that will be presented at the American Society of Clinical Oncology Annual Meeting in Chicago, IL. However, the population-level benefit will remain low unless more people get vaccinated.

Young adults in the United States who received at least one dose of the quadrivalent form of Merck's human papillomavirus (HPV) vaccine Gardasil experienced an estimated 88% reduction in the prevalence of detectable HPV in their oral cavities, according to study data that will be presented at next month's American Society of Clinical Oncology Annual Meeting in Chicago, IL.

Buoyed by the findings, specialists say a renewed focus on HPV prevention could help stem the growing epidemic of HPV-related cancers of the tongue and tonsils, especially among men. There are two caveats, though: First, the direct link between immunization and cancer risk has yet to be demonstrated. Second, “very few people are taking the vaccine and the potential benefit is not going to make a darned bit of difference unless we get the vaccination rates up,” says William Armstrong, MD, from the University of California, Irvine.

In the new study, a team led by Maura Gillison, MD, PhD, from The University of Texas MD Anderson Cancer Center in Houston, who conducted the work while at The Ohio State University in Columbus, evaluated the impact of prophylactic vaccination on oral HPV infection in a cohort of 2,627 individuals ages 18 to 33 in the Centers for Disease Control and Infection's (CDC) national health survey. Infection was measured through DNA contained within cells captured in a mouth rinse. The researchers found that between 2011 and 2014, only 0.11% of those vaccinated had signs of oral HPV, compared with 1.61% of those not vaccinated.

However, vaccination rates were low, with just 29% of women and 7% of men having had at least one dose of Gardasil. In the population as a whole, that reduced the oral HPV burden by only 25% for women and 7% for men. But Gillison notes that “vaccine uptake is higher now than it was” during the study period—with 63% of adolescent girls and 50% of adolescent boys starting an HPV vaccine series, according to the CDC—so there's “tremendous potential to prevent oral infections,” she says.

Most experts anticipate that the lower infection rates will translate into a reduction in HPV-related head and neck cancer. But Carole Fakhry, MD, from Johns Hopkins School of Medicine in Baltimore, MD, cautions against assuming that what's true of anal and cervical cancers—diseases for which prospective data clearly show a protective benefit of vaccination—will also be true of oral cancers.

“These results are promising,” Fakhry says, “but point to the need to further study vaccination prospectively with a specific focus on the long-term natural history of oral HPV infection.”

One such prospective study took place recently in Costa Rica. The prevalence of HPV in the oral cavity was 93% lower in women who received an HPV vaccine compared with women who received one for hepatitis A. Another prospective study, published last year, also documented the link between HPV and oropharyngeal cancer, showing that prior oral infection with the highest-risk strain of HPV was associated with a 22.4-fold increased chance of developing squamous cell carcinoma of the oropharynx.

Those results, combined with Gillison's new data, convince Vikas Mehta, MD, from Montefiore Medical Center in the Bronx, NY, that HPV vaccination can prevent oropharyngeal cancers. Of course, he'd prefer to see that inference proven in a prospective trial. However, without any oral biomarkers similar to the precancerous lesions and warts that can indicate cervical or anal cancer, he thinks such trials would be “extremely difficult,” lasting 20 or 30 years and requiring tens of thousands of participants.

“We could wait that long,” Mehta says, “or we could say, ‘Look, this evidence is pretty robust and now is the time’” to start promoting the vaccine for preventing head and neck cancers. –Elie Dolgin