https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673607614160.pdf

Human papillomavirus and cervical cancer

Centers for Disease Control and Prevention (CDC) : Advisory Committee on Immunization Practices (ACIP) : Quadrivalent human papillomavirus vaccine : recommendations of the Advisory Committee on Immunization Practices (ACIP)

BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.

/pdf/quadrivalent-vaccine-against-human-papillomavirus-to-prevent-bjulb1tioi.pdf

Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions

Background A phase 3 trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine in preventing anogenital diseases associated with human papillomavirus (HPV) types 6, 11, 16, and 18. Methods In this randomized, placebo-controlled, double-blind trial involving 5455 women between the ages of 16 and 24 years, we assigned 2723 women to receive vaccine and 2732 to receive placebo at day 1, month 2, and month 6. The coprimary composite end points were the incidence of genital warts, vulvar or vaginal intraepithelial neoplasia, or cancer and the incidence of cervical intraepithelial neoplasia, adenocarcinoma in situ, or cancer associated with HPV type 6, 11, 16, or 18. Data for the primary analysis were collected for a per-protocol susceptible population of women who had no virologic evidence of HPV type 6, 11, 16, or 18 through 1 month after administration of the third dose. Results The women were followed for an average of 3 years after administration of the first dose. In the per-proto...

/pdf/quadrivalent-vaccine-against-human-papillomavirus-to-prevent-36rchbohnq.pdf

Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases.

This report summarizes the epidemiology of human papillomavirus (HPV) and associated diseases, describes the licensed HPV vaccines, provides updated data from clinical trials and postlicensure safety studies, and compiles recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) for use of HPV vaccines. Persistent infection with oncogenic HPV types can cause cervical cancer in women as well as other anogenital and oropharyngeal cancers in women and men. HPV also causes genital warts. Two HPV vaccines are licensed in the United States. Both are composed of type-specific HPV L1 protein, the major capsid protein of HPV. Expression of the L1 protein using recombinant DNA technology produces noninfectious virus-like particles (VLPs). Quadrivalent HPV vaccine (HPV4) contains four HPV type-specific VLPs prepared from the L1 proteins of HPV 6, 11, 16, and 18. Bivalent HPV vaccine (HPV2) contains two HPV type-specific VLPs prepared from the L1 proteins of HPV 16 and 18. Both vaccines are administered in a 3-dose series. ACIP recommends routine vaccination with HPV4 or HPV2 for females aged 11 or 12 years and with HPV4 for males aged 11 or 12 years. Vaccination also is recommended for females aged 13 through 26 years and for males aged 13 through 21 years who were not vaccinated previously. Males aged 22 through 26 years may be vaccinated. ACIP recommends vaccination of men who have sex with men and immunocompromised persons (including those with HIV infection) through age 26 years if not previously vaccinated. As a compendium of all current recommendations for use of HPV vaccines, information in this report is intended for use by clinicians, vaccination providers, public health officials, and immunization program personnel as a resource. ACIP recommendations are reviewed periodically and are revised as indicated when new information and data become available.

/pdf/human-papillomavirus-vaccination-recommendations-of-the-28czmnevd6.pdf

Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP).

Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16–23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrolment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy=100%; 95% CI:12–100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.

/pdf/high-sustained-efficacy-of-a-prophylactic-quadrivalent-human-s8r9q47fx2.pdf

High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up

A. Andersson-Ellstrom

Papers

High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up