Prevention is now a reality : reducing the burden of cervical cancer and other HPV disease through vaccination

Sylvester, Gregg C

Abstract

OBJECTIVE
The lifetime risk of HPV infection exceeds 50%. HPV infection causes cervical cancer; a subset of vulvar and vaginal cancers; cervical, vulvar, and vaginal dysplastic lesions; and genital warts. HPV 16/18 cause 70% of cervical pre-cancers and cancers, HPV 6/11 cause 90% of genital warts, and together HPV 6/11/16/18 cause 35-50% of low grade but clinically important cervical dysplasias. A vaccine targeting these types will substantially reduce the burden of HPV disease. The following is a review of the efficacy, immunogenicity and safety of the Merck Quadrivalent HPV vaccine with updated post-licensure data.
METHODS
Merck Quadrivalent HPV vaccine is the only quadrivalent HPV (Types 6/11/16/18) L1 virus-like-particle (VLP) vaccine. Efficacy trials in 20,845 16-26 year old women were conducted, with primary efficacy analyses in per-protocol populations (subjects received 3 doses; were HPV seronegative at Day 1 and HPV DNA negative through completion of vaccination). Immunogenicity studies were also conducted in 2794 boys and girls, aged 9-15 years. For all studies, serum anti-HPV levels were measured by type-specific immunoassays and summarized as anti- HPV-6, 11, 16, and 18 neutralizing antibody geometric mean titers (GMTs) and seroconversion rates. Adverse experiences were recorded (diary card).
RESULTS
At the time of licensure, the prophylactic efficacy of a 3-dose regimen of Merck Quadrivalent HPV vaccine against HPV 16/18-related moderate/high grade cervical precancer and noninvasive cervical cancer was 100% (0 cases vaccine versus 53 cases placebo). With an additional year of follow-up, prophylactic efficacy against this endpoint was 99% (95% confidence intervals [CI]: 93%, 100%; 1 case vaccine versus 85 cases placebo), and efficacy specifically against adenocarcinoma in situ was 100% (95% CI: 31%, 100%; 0 cases vaccine versus 7 cases placebo). Updated prophylactic efficacy against HPV 6/11/16/18-related external genital lesions (vulvar/vaginal precancers and warts) was 99% (95% CI : 96%, 100%; 2 cases vaccine versus 189 cases placebo). In adult women, vaccine-induced anti-HPV responses were detected in 99.5% of subjects one month Postdose 3. Through up to 5 years of follow-up, anti-HPV GMTs remained at or above those measured following clearance of HPV infection and efficacy was maintained. A robust immune memory was evidenced by the rapid and strong increase in GMTs triggered by the administration of an immune challenge at 4.5 years post-dose 3. In a separate study, antibodies triggered by Merck Quadrivalent HPV vaccine were found to neutralize in-vitro HPV 31 and 45 pseudovirions, pointing to a potential for protection against additional HPV types. In adolescents aged 9-15 years, Merck Quadrivalent HPV vaccine was highly immunogenic. GMTs in girls and boys were 1.7-2.7 fold higher than those observed in young adult women. In all studies, vaccine was generally well-tolerated, though a slightly higher proportion of subjects reported one or more injection site adverse experiences than the placebo group.
CONCLUSION
Vaccination of adolescents and young adults with Merck Quadrivalent HPV vaccine is expected to greatly reduce the burden of cervical and other genital cancers, dysplasia, and genital warts.

Prevention is now a reality : reducing the burden of cervical cancer and other HPV disease through vaccination

Abstract

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