Efficacy of the human papillomavirus (HPV) vaccine

PICHON-RIVIERE A,; AUGUSTOVSKI, F; ALCARAZ A; BARDACH, ARIEL; COLANTONIO, LISANDRO; GARCIA MARTÍ, SEBASTIAN; GLUJOVSKY, D; LOPEZ, A; REGUEIRO, A

Documentos de Evaluación de Tecnologías Sanitarias

IECS

Año: 2006 p. 1 - 30

1668-2793

This report aims to assess the efficacy of HPV vaccine.A search was performed on the main literature databases, on the web site of the York Centre for Reviews and Dissemination (CRD), U.S Medicare and Medicaid, on the Internet's general search engines and metasearch engines, health technology assessment agencies and private health sponsors. Systematic reviews, meta-analysis, controlled randomized clinical trials, observational studies, health technology assessments, clinical practice guidelines and coverage policies from other health systems were searched. Priority was given to systematic and narrative reviews and randomized clinical trials (RCT). Case series were also included. Web sites from the main local and U.S. medical societies and associations related to the topic were also consulted.Bivalent vaccine (types 16 and 18) The efficacy of the vaccine was evaluated in a double blind, placebo controlled RCT in 1113 women, from 15 to 25 years of age, performed in the U.S., Canada and Brazil. The follow-up was 4.5 years. Seroconversion occurred in 95% of the women. Protection against persistent infection (more than a year) took place in 100% of the women who received vaccine. The efficacy regarding the incidence of infection (new infection) was 96.9%. More than 99% of the patients vaccinated sustained the level of protective antibodies for more than 4.5 years, against both viral types studied. No case of cervical intraepithelial neoplasia (CIN) was observed in the vaccine group, versus 8 cases reported for the placebo group. In another study conducted in 776 women 15-55 years old with a 4.5 year follow-up, the bivalent vaccine showed similar results including women in the elder group (46 to 55 years old).Tetravalent vaccine (types 6; 11; 16 and 18): The efficacy of the tetravalent vaccine was assessed in a Phase IIB RCT conducted in 552 women (average age 20 years old) carried out in the U.S., Europe and Brazil. The follow-up was over 48 months. The results were statistically significant with p <0.001 for the following observations: Overall protection against persistent infection for types 16 and 18 occurred in 89% of the patients with 100%, 86% and 89% for types 6, 16 and 18, respectively. There were no cases of HPV11. Protection against CIN occurred in 100% of the intervention group. Seven cases of CIN were seen in the placebo group. Protection against all external genital warts caused by HPV 6-11 took place in 100 % of the participants; 7 were seen in the placebo group. Vaccine efficacy against the 4 types was 90% (95% CI 71-97%). In a Phase III double blind RCT including more than 12,000 women 16-26 years old, with a two-year follow-up, 9 cases of CIN or adenocarcinoma in situ were detected in the vaccine group, whereas 143 in the placebo (94% efficacy). Nine cases of external genital warts were observed in the vaccine group, versus 174 in the placebo (95% efficacy). The vaccine was well tolerated and there were no serious adverse effects.At present, there are several international Phase III RCTs being performed for both vaccines; on the whole they include more than 40,000 patients and they will continue in the next coming years.The studies identified suggest that the vaccine strategy in young women would have a cost-effectiveness within the acceptable range for developed countries (U$S 20,000 to 60,000 per QALY gained), whereas no studies were identified in our country.