Reduced Prevalence of Oral Human Papillomavirus (HPV) 4 Years after Bivalent HPV Vaccination in a Randomized Clinical Trial in Costa Rica

Abstract

BackgroundHuman papillomavirus (HPV) infection, particularly with type 16, causes a growing fraction of oropharyngeal cancers, whose incidence is increasing, mainly in developed countries. In a double-blind controlled trial conducted to investigate vaccine efficacy (VE) of the bivalent HPV 16/18 vaccine against cervical infections and lesions, we estimated VE against prevalent oral HPV infections 4 years after vaccination.Methods and FindingsA total of 7,466 women 18–25 years old were randomized (1∶1) to receive the HPV16/18 vaccine or hepatitis A vaccine as control. At the final blinded 4-year study visit, 5,840 participants provided oral specimens (91·9% of eligible women) to evaluate VE against oral infections. Our primary analysis evaluated prevalent oral HPV infection among all vaccinated women with oral and cervical HPV results. Corresponding VE against prevalent cervical HPV16/18 infection was calculated for comparison. Oral prevalence of identifiable mucosal HPV was relatively low (1·7%). Approximately four years after vaccination, there were 15 prevalent HPV16/18 infections in the control group and one in the vaccine group, for an estimated VE of 93·3% (95% CI = 63% to 100%). Corresponding efficacy against prevalent cervical HPV16/18 infection for the same cohort at the same visit was 72·0% (95% CI = 63% to 79%) (p versus oral VE = 0·04). There was no statistically significant protection against other oral HPV infections, though power was limited for these analyses.ConclusionsHPV prevalence four 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.ClinicalTrials.gov, Registry number NCT00128661

Tonsillectomy and Incidence of Oropharyngeal Cancers

“…Importantly, oropharyngeal cancers (particularly HPV-positive oropharyngeal cancers) are projected to become the most common head and neck cancer in the coming 15 to 20 years (6-8), underscoring the need for prevention strategies. At this time, prophylactic HPV vaccination holds the greatest promise to curb this rise (29). We also show that tonsillectomy was associated with substantial reductions in tonsil cancer risk.…”

The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications

“…Gardasil (Merck) and Cervarix (GlaxoSmithKline) are two commercially available HPV vaccines shown to be effective for cervical carcinoma in large randomized trials (60). Their role in prevention of HPV-related oropharyngeal cancers is currently being evaluated, with one trial showing promising results (61). A trial testing efficacy of Gardasil in 11-year-old boys in Mexico City is underway (NCT02382900).…”

The Growing Epidemic of HPV-Positive Oropharyngeal Carcinoma: A Clinical Review for Primary Care Providers

“…While the specific effect of HPV vaccination on HPVϩ OPSCC itself has not been evaluated yet, the currently available HPV-16/-18 vaccine has recently been found to be even more efficacious against oral HPV infection (vaccine efficacy, 93.3%; 95% CI, 62.5-99.7%) than against cervical HPV infection (vaccine efficacy, 72.0%; 95% CI, 63.0 -79.1%) in a randomized trial of young women in Costa Rica. 18 This efficacy is likely to also be observed in men. In a 2008 analysis of the cost-effectiveness of routine HPV vaccination of 12-year-old girls, the cost per quality-adjusted life-year was $3,906 when cervical, anal, vaginal, vulvar, and oropharyngeal cancers, as well as herd immunity effects, were considered.…”