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HPV Vaccine Protects Against Anal Infection in Women

 

The bivalent human papillomavirus (HPV) vaccine (Cervarix, GlaxoSmithKline), which is indicated for the prevention of cervical diseases caused by infection with HPV-16 and HPV-18, also provides "strong protection" against anal infection with these HPV types in young women, according to authors of new trial conducted in Costa Rica.

The study is the first to show that an HPV vaccine can prevent anal HPV infection in females.

However, the protection was not as effective at the anus as it was in the cervix, which was used as a comparator. The women, who were vaccinated at ages 18 to 25 years, were tested 4 years later for anal and cervical HPV-16 and HPV-18 infections to assess the vaccine’s efficacy.

In a cohor

t of 4210 women, vaccine efficacy at the anus against prevalent HPV-16/18 infection was 62% compared with 76.4% in the cervix (= .031 for interaction by anatomical site).

The efficacy was higher in a subset of women in the study who received their vaccination before exposure to HPV.

In this restricted cohort of 1989 women, vaccine efficacy against anal HPV-16/18 infection was 83.6%, which was "similar" to vaccine efficacy of 87.9% in the cervix.

HPV causes most anal cancer, which is a "rare" disease, point out the study authors, led by Amiee Kreimer, MD of the National Cancer Institute in Bethesda, Maryland. An estimated 75% to 80% of HPV-associated cancers are caused by HPV-16 or HPV-18.

The study's findings are welcome news for women, suggest 2 experts who penned an editorial that accompanies the study online in The Lancet Oncology.

"Women have twice the incidence of anal cancer as men...and are predisposed to anal HPV infection if they already have cervical neoplasia, irrespective of anal intercourse," write Diane Harper, MD, and Stephen Vierthaler, MD, of University of Missouri–Kansas City School of Medicine.

However, the findings beg the question of how HPV vaccination should be used. "The public health benefit of prophylactic HPV vaccines for anal cancer is an open question," say the pair.

According to the editorialists, the natural history of the infection is different in distinct populations. HPV infections are both more common and virulent in men who have sex with men and in immunosuppressed men. For these reasons, vaccinating men who have sex with men for the prevention of anal cancer is good public health policy, they argue. Another study of the quadrivalent vaccine Gardasil has shown evidence of efficacy against anal HPV infection in men who have sex with men.

However, the cost-effectiveness of vaccination for men and women "pivot on the duration of vaccine efficacy," say the editorialists.

"Without duration of efficacy of at least 15 years, cancers will not be prevented for women or men who have sex with men, only postponed," write Dr. Harper and Dr. Vierthaler.

The study authors also acknowledge the wild card of duration.

"HPV vaccines have great potential for prevention of a large proportion of HPV-associated cancers at the anus and other anatomical sites...assuming adequate duration of protection," write the study authors.

In the new study, the median follow-up from vaccination was 4.1 years.

As a result, more study is needed, say the study authors. "Further, showing that the protection lasts beyond the 4 years assessed in this study will be important to ensure women are protected during the ages of higher exposure."

Randomized Controlled Trial

The 7466 study participants were residents of Guanacaste and selected areas of Puntarenas, Costa Rica. They were aged 18 to 25 years and not pregnant or breastfeeding. The young women were randomly assigned (1:1) to receive the HPV vaccine Cervarix or a control hepatitis A vaccine (modified preparation of Havrix, GlaxoSmithKline). Vaccines were administered in three 0.5 mL doses at enrollment, 1 month, and 6 months.

Four years after vaccination, 6352 women returned for the final study visit. They were supposed to provide a one-time anal specimen for assessment of vaccine efficacy against anal HPV-16/18 infection at this time. However, many declined, at that 4-year visit, to undergo the one-time anal specimen collection, which was performed with a dry swab. Also, 384 women had not yet had sexual intercourse and were also not included. As a result, the full cohort was reduced to 4210 women.

An additional analysis was performed in a restricted cohort of 1989 women who were HPV naive, and this was possible because testing was performed before enrollment. All of the young women were tested for evidence of HPV-16 and HPV-18 in both cervical tissue and blood cells.

Women with and without evidence of HPV infection at enrollment were allowed to participate in the study.

At 4 years, the prevalence of HPV-16/18 infections was not common — in either the anus or cervix and in either vaccinated women or controls.

For instance, in the full cohort, among the 2103 young women who received the HPV vaccine, there were 47 infections of HPV-16/18 in the anus (2.2% prevalence). Among the 2107 controls, there were 124 such infections (5.9% prevalence).

These prevalence findings were then converted and reported as vaccine efficacy. In this case, vaccine efficacy at the anus against prevalent HPV-16/18 infection was 62% in the full cohort, as noted above.

The study also showed, for the first time, that this HPV vaccine provides cross-protective efficacy that was statistically significant against other cancer-causing HPV types 31 and 45 at a site other than the genitalia, "providing confirmation that the protection afforded by the bivalent HPV vaccine goes beyond the HPV types included in the vaccine formulation," say the study authors.

At the 4-year visit, the women also completed a questionnaire that included a yes/no question about engaging in anal sex.

Women in the full cohort who reported anal sex had an anal vaccine efficacy of 73.9%, whereas those who did not report anal sex had an anal vaccine efficacy of 55.3% (P = .13 for interaction by anal sex status,). In contrast, cervical vaccine efficacy was similar whether or not the women reported engaging in anal sex.

In the restricted cohort, these findings were not replicated: anal and cervical vaccine efficacy estimates were more similar (range, 80%-88%), regardless of anal sex status.

The study authors attempted to explain how women who did not have anal sex ended up with anal infections and lower vaccine efficacy. "One possibility might be that a greater proportion of the anal infections detected in women who did not have anal sex might be superficial virions shed from genital sites for which the vaccine would not be expected to protect," they write.

The study was funded by the National Cancer Institute. Two coauthors report that they are named inventors on US government–owned HPV vaccine patents that are licensed to GlaxoSmithKline and Merck and for which the National Cancer Institute receives licensing fees. They are entitled to limited royalties as specified by federal law. The other authors declare that they have no conflicts of interest. The institutions at which Dr Harper has performed HPV vaccine trials have received funding from Merck and GlaxoSmithKline. She has also received honoraria for speaking and for participation on advisory boards in the past from both companies.

Lancet Oncol. 2011;12:862-870, 828-829. Abstract

 

 

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