Speculation overinflates long-term efficacy of vaccine for anal dysplasia

Patients with severe anal warts and anal intraepithelial neoplasia can need general surgery, which might still result in a high recurrence rate of disease. Anal disease associated with human papillomavirus (HPV) aff ects both HIV-negative and HIVpositive men and women, with HIVpositive patients developing more severe disease in a shorter time than those without HIV. Randomised trials such as the one by Olivier Richel and colleagues are increasingly necessary to guide appropriate treatments. The conclusion off ered by Ulrike Wieland and colleagues—that prophylactic HPV vaccination of boys might reduce anal intra epithelial neoplasia and anal cancer—is misleading to researchers, clinicians, and patients. Although mathematical models show that vaccination of males with prophylactic HPV vaccines increases the disruption of HPV transmission and infection among the entire population, little evidence exists of the quadrivalent vaccine’s long-term effi cacy for treatment of anal disease. Long-term effi cacy of the vaccine depends on antibody titres and memory B-cell responses in the human host. Studies of the quadrivalent vaccine show that immunogenicity diff ers by sex. Males lose detectable antibody titres to HPV 18, HPV 6, and HPV 11 signifi cantly faster than females after only 24 months from the fi rst of three vaccine doses (fi gure). It takes 8·5 years to see a 14% loss of detectable anti-HPV 16 titres in females, but corresponding longterm studies (of at least 8·5 years) to determine the full extent of antiHPV titre loss in males have not yet been undertaken. Nonetheless, if the vaccination of males at 11 years of age results in nearly 40% losing detectable titres to one of the two cancer-causing types at 13 years of age, it is suspect that long-term effi cacy can result in a signifi cant reduction in anal cancers. Investigations in females have looked at the antibody and memory B-cell response in recipients of the quadrivalent vaccine 24 months after the fi rst vaccine dose, fi nding memory B-cell responses to HPV 16 in only 67% of the population and to HPV 18 in only 53% of the population. No studies of memory B-cell response in males given the quadrivalent vaccine have been registered. Without long-term comprehensive work to understand the immunogenicity, effi cacy, and safety of the quadrivalent vaccine in males and in males who have sex with males (one of the highest risk populations for anal cancer), little chance for primary prevention of these cancers exists. Continuation of the intense work on chemotherapy, immune modulators, and other therapeutic vaccines for individuals with recalcitrant HPV anal disease is necessary. This work cannot be stopped in the hope that the prophylactic vaccine will remain eff ective in the next generation.