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HPV Vaccine Prevents Oral Infection, May Lower Risk of Mouth and Throat Cancer

Vaccination against human papillomavirus (HPV) types 16 and 18 reduced oral infection by more than 90% in a large study in Costa Rica, which is likely to bring down the rate of mouth and throat cancers in years to come, according to a report in the July 17, 2013, online edition of PLoS ONE.

There are more than 100 known types of HPV, and most people start getting infected soon after they become sexually active. Many individuals naturally clear the virus, but in others it persists and can cause abnormal cell changes. Types 16 and 18 are the most likely to cause cervical, anal, vulva, penis, and probably oral cancer, while types 6 and 11 are the main causes of genital warts. According to the U.S. Centers for Disease Control and Prevention (CDC), 8400 cases of oropharyngeal cancer annually are attributable to HPV.

Studies have established that vaccines can dramatically reduce genital and anal HPV infection. There are 2 approved vaccines: Cervarix is effective against types 16 and 18, while Gardasil is effective against 16, 18, 6, and 11. Several countries instituted routine HPV vaccination for young women in the 1990s, and more recently for young men as well. Epidemiological studies have shown reduced rates of genital warts and pre-cancerous genital and anal cell changes (dysplasia or neoplasia) several years after widespread adoption.

Rolando Herrero with the World Health Organization's International Agency for Research on Cancer and colleagues conducted a randomized controlled trial to investigate whether thebivalent HPV16/18 vaccine is also protective against oral HPV infection.

The analysis included 7466 women, age 18 to 25 years, enrolled in the NCI Costa Rica Vaccine Trial, sponsored by the U.S. National Cancer institute, which looked at prevention of cervical HPV infection. Participants were randomly assigned (1:1) to receive the HPV16/18 vaccine or a hepatitis A vaccine as a control. Follow-up continued for 4 years. At the final blinded study visit, 5840 women (92%) provided throat specimens for analysis.

Results

• Overall prevalence of identifiable HPV in oral mucosa was relatively low, at 1.7%.
• Approximately 4 years after vaccination, there was just 1 case of HPV16 or HPV18 infection in the vaccinated group, compared with 15 infections in the control group.
• The represented a vaccine efficacy or protection rate of 93.3%.
• Corresponding efficacy against cervical HPV16/18 infection was 72.0% for the same cohort at the same visit.
• There was no statistically significant change in rates of oral infection with other HPV types not included in the vaccine.

Based on these findings, the study authors concluded, "HPV prevalence 4 years after vaccination with the ASO4-adjuvanted HPV16/18 vaccine was much lower among women in the vaccine arm compared to the control arm, suggesting that the vaccine affords strong protection against oral HPV16/18 infection, with potentially important implications for prevention of increasingly common HPV-associated oropharyngeal cancer."

This is the first study to report on the efficacy of an HPV vaccine against oral infection, they noted in their discussion.

As the study was designed to evaluate cervical HPV infection, it did not measure oral HPV infection status at baseline, and therefore could not determine how many new infections occurred, only prevalence at the end of follow-up. The researchers said efficacy might be even higher in an analysis limited to women known to be uninfected with HPV16 and HPV18 at baseline.

Since it takes a long time for cancer to develop, not all infections with high-risk HPV lead to malignancies, and mouth and throat cancers are relatively rare, the study was not able to show a reduction in cancer itself. In addition, there are no established precursor or pre-cancerous abnormalities for oral cancers, similar to high-grade intraepithelial neoplasia or squamous intraepithelial lesions for cervical or anal cancer.

"Until now, there have been no data on efficacy of any of the HPV vaccines for prevention of oral HPV infection, and this remains the case in men," the authors summarized. "However, it is likely that the protection we observed among women will also be present in men, as [viral efficacy] of both vaccines has been demonstrated against HPV infections among men and women at all mucosal sites evaluated."

Our results, they added, "suggest that administration of the HPV vaccine will guard against oral infection by the HPV types responsible for the vast majority of HPV-related [oropharyngeal cancer], and open the possibility of primary prevention of these increasingly common malignancies."

7/24/13

Reference

R Herrero, W Quint, A Hildesheim, et al. Reduced Prevalence of Oral Human Papillomavirus (HPV) 4 Years after Bivalent HPV Vaccination in a Randomized Clinical Trial in Costa Rica. PLoS ONE 8(7):e68329. July 17, 2013(Epub ahead of print).

Other Source

National Cancer Institute.HPV vaccine shown to also protect against oral HPV infection. NCI News Note. July 17, 2013.