ArticlesEfficacy of a bivalent HPV 16/18 vaccine against anal HPV 16/18 infection among young women: a nested analysis within the Costa Rica Vaccine Trial
Introduction
Anal cancer remains rare, with an annual age-standardised incidence in the general population of about 1·5 per 100 000 for women;1 but rates have roughly doubled in recent decades in many countries, including the USA and several European nations.2, 3, 4, 5 The absolute burden of anal cancer is higher for women than men,3, 4, 5 yet, anal cancer disproportionately affects HIV-positive individuals and men who have sex with men, even if they are HIV-negative.6, 7
Human papillomavirus (HPV) causes most anal cancers, with an estimated 75–80% of HPV-associated anal cancers caused by HPV types 16 or 18.8, 9 For other HPV-associated extracervical cancers, including cancers of the oropharynx, vagina, vulva, and penis,9 variable proportions are caused by HPV infection but, when HPV is present, HPV 16 is the predominant type implicated (75–95% of the HPV-associated cancers).9
Two vaccines prevent infection with HPV 16 and HPV 18: the bivalent HPV 16 and HPV 18 vaccine (Cervarix, GlaxoSmithKline Biologicals, Rixensart, Belgium)10 and the quadrivalent HPV 6, 11, 16, and 18 vaccine (Gardasil, Merck, Whitehouse Station, NJ, USA).11 In women, vaccine efficacy has been shown against cervical precancer (both vaccines)10, 11 and vaginal and vulvar HPV infections and related diseases (quadrivalent only).12 For men, vaccine efficacy has been shown against penile, perianal, perineal HPV infections as a combined endpoint (quadrivalent only).13 To our knowledge, direct evidence for efficacy against anal HPV infection has only been shown in one unpublished trial14 of the quadrivalent vaccine in about 600 men who have sex with men. The bivalent vaccine has not been assessed at extracervical sites.
We assessed the efficacy of the bivalent HPV vaccine to decrease anal HPV infection using data nested in a community-based randomised trial of cervical vaccine efficacy in young adult women.
Section snippets
Patients
Women included in this study were participants in a double-blind, randomised clinical trial initially designed to assess the efficacy of a bivalent HPV vaccine against persistent type-specific infection with HPV 16, HPV 18, or both (from here on referred to as HPV 16/18) and associated precancerous lesions at the cervix.15, 16 The study enrolled women residing in Guanacaste and selected areas of Puntarenas, Costa Rica, identified via a census, between June 28, 2004, and Dec 21, 2005. Main
Results
Of the 7466 women randomly assigned to HPV or control vaccines, 6352 attended the 4-year study visit (figure). 384 of women were virgins and therefore not eligible for anal specimen collection. Another 1744 women refused anal specimen collection. After exclusion of 14 missing anal HPV results because of inadequate specimen volume, the full analytical cohort consisted of 4210 women. Median follow-up time was 54·2 months (4·5 years) and was similar between groups (HPV 54·2 months [range
Discussion
A randomised analysis of data from our community-based HPV vaccine trial in Costa Rica shows that the bivalent HPV vaccine is efficacious against prevalent anal HPV 16/18 infections in young women measured 4 years after vaccination. We also show, to our knowledge for the first time, evidence of cross-protection against a composite endpoint of HPV types 31/33/45 at an extragenital site; providing confirmation that the protection afforded by the bivalent HPV vaccine goes beyond the HPV types
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