HPV vaccine against anal HPV infection and anal intraepithelial neoplasia.
BACKGROUND
The rate of anal cancer is increasing among both women and men, particularly men who have sex with men. Caused by infection with human papillomavirus (HPV), primarily HPV type 16 or 18, anal cancer is preceded by high-grade anal intraepithelial neoplasia (grade 2 or 3). We studied the safety and efficacy of quadrivalent HPV vaccine (qHPV) against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 infection in men who have sex with men.


METHODS
In a substudy of a larger double-blind study, we randomly assigned 602 healthy men who have sex with men, 16 to 26 years of age, to receive either qHPV or placebo. The primary efficacy objective was prevention of anal intraepithelial neoplasia or anal cancer related to infection with HPV-6, 11, 16, or 18. Efficacy analyses were performed in intention-to-treat and per-protocol efficacy populations. The rates of adverse events were documented.


RESULTS
Efficacy of the qHPV vaccine against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 was 50.3% (95% confidence interval [CI], 25.7 to 67.2) in the intention-to-treat population and 77.5% (95% CI, 39.6 to 93.3) in the per-protocol efficacy population; the corresponding efficacies against anal intraepithelial neoplasia associated with HPV of any type were 25.7% (95% CI, -1.1 to 45.6) and 54.9% (95% CI, 8.4 to 79.1), respectively. Rates of anal intraepithelial neoplasia per 100 person-years were 17.5 in the placebo group and 13.0 in the vaccine group in the intention-to-treat population and 8.9 in the placebo group and 4.0 in the vaccine group in the per-protocol efficacy population. The rate of grade 2 or 3 anal intraepithelial neoplasia related to infection with HPV-6, 11, 16, or 18 was reduced by 54.2% (95% CI, 18.0 to 75.3) in the intention-to-treat population and by 74.9% (95% CI, 8.8 to 95.4) in the per-protocol efficacy population. The corresponding risks of persistent anal infection with HPV-6, 11, 16, or 18 were reduced by 59.4% (95% CI, 43.0 to 71.4) and 94.9% (95% CI, 80.4 to 99.4), respectively. No vaccine-related serious adverse events were reported.


CONCLUSIONS
Use of the qHPV vaccine reduced the rates of anal intraepithelial neoplasia, including of grade 2 or 3, among men who have sex with men. The vaccine had a favorable safety profile and may help to reduce the risk of anal cancer. (Funded by Merck and the National Institutes of Health; ClinicalTrials.gov number, NCT00090285.).
Department of Medicine, University of California at San Francisco, Box 0654, San Francisco, CA 94143, USA. joel.palefsky@ucsf.edu
Joel M
JM
Palefsky
Anna R
AR
Giuliano
Stephen
S
Goldstone
Edson D
ED
Moreira
Carlos
C
Aranda
Heiko
H
Jessen
Richard
R
Hillman
Daron
D
Ferris
Francois
F
Coutlee
Mark H
MH
Stoler
J Brooke
JB
Marshall
David
D
Radley
Scott
S
Vuocolo
Richard M
RM
Haupt
Dalya
D
Guris
Elizabeth I O
EI
Garner
D000293:Adolescent; D000328:Adult; D001004:Anus Diseases / Q000517:prevention & control* / Q000821:virology; D001005:Anus Neoplasms / Q000517:prevention & control / Q000821:virology; D002278:Carcinoma in Situ / Q000517:prevention & control* / Q000821:virology; D004311:Double-Blind Method; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D052140:Human papillomavirus 11; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D052163:Human papillomavirus 6; D006801:Humans; D008297:Male; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines; D055815:Young Adult
D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines