A Pooled Analysis of Continued Prophylactic Efficacy of Quadrivalent Human Papillomavirus (Types 6/11/16/18) Vaccine against High-grade Cervical and External Genital Lesions

Department of Virus, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society/Rigshospitalet, Copenhagen, Denmark.
Cancer Prevention Research (Impact Factor: 4.44). 10/2009; 2(10):868-78. DOI: 10.1158/1940-6207.CAPR-09-0031
Source: PubMed


Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18-related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions based on end-of-study data from three clinical trials. Additionally, we stratify vaccine efficacy by several baseline characteristics, including age, smoking status, and Papanicolaou (Pap) test results. A total of 18,174 females ages 16 to 26 years were randomized and allocated into one of three clinical trials (protocols 007, 013, and 015). Vaccine or placebo was given at baseline, month 2, and month 6. Pap testing was conducted at regular intervals. Cervical and anogenital swabs were collected for HPV DNA testing. Examination for the presence of vulvar and vaginal lesions was also done. Endpoints included high-grade cervical, vulvar, or vaginal lesions (CIN 2/3, VIN 2/3, or VaIN 2/3). Mean follow-up time was 42 months post dose 1. Vaccine efficacy against HPV 6/11/16/18-related high-grade cervical lesions in the per-protocol and intention-to-treat populations was 98.2% [95% confidence interval (95% CI), 93.3-99.8] and 51.5% (95% CI, 40.6-60.6), respectively. Vaccine efficacy against HPV 6/11/16/18-related high-grade vulvar and vaginal lesions in the per-protocol and intention-to-treat populations was 100.0% (95% CI, 82.6-100.0) and 79.0% (95% CI, 56.4-91.0), respectively. Efficacy in the intention-to-treat population tended to be lower in older women, women with more partners, and women with abnormal Pap test results. The efficacy of quadrivalent HPV vaccine against high-grade cervical and external anogenital neoplasia remains high through 42 months post vaccination.

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    • "These vaccines protect against HPV types 16 and 18 (Cervarix) and HPV types 6, 11, 16, and 18 (Gardasil). Both vaccines are highly effective against HPV 16/18, and Gardasil has shown greater than 98% efficacy against HPV 6/11-associated genital warts [6–8]. Although these vaccines will likely reduce the incidence of HPV-associated diseases in the long-term, they do not protect against the other high-risk HPV types and are ineffective at treating established infections [9,10]. "
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    • "Vaccination also provided high protection for the TVC group, which includes individuals previously exposed to HPV, against HPV16/18 type associated CIN2 (>54.8%), CIN3 (>45.1%) and AIS (>60%) [7,8,10] (Table 2). HPV vaccination is highly efficient at reducing both HPV 16/18 and associated pre-cancerous lesions, particularly when given to a HPV naïve population such as that targeted by mass vaccination programs. "
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    • "For the bivalent vaccine, efficiency for prevention of HPV-16/18-related cervical intraepithelial neoplasia (CIN) was 98% [Paavonen et al. 2009]. For the quadrivalent vaccine , the efficacy for CIN was 100% for all four HPV subtypes, in addition to a 98.9% reported efficacy for prevention of HPV-6/11/16/18-related genital warts, and 100% efficacy for HPV-16/18- related vulval and vaginal intraepithelial neoplasia [Kjaer et al. 2009; Munoz et al. 2009]. "
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