July 2006

Literature Review

Prophylactic human papillomavirus vaccines
Go to full text in PubMed: Lowy DR, Schiller JT. J Clin Invest 2006;116;1167

This is a report from the National Cancer Institute of the NIH dealing with the exciting development of vaccines for human papillomavirus (HPV). These vaccines are being developed by Merck and Glaxo. Both target HPV16 and HPV18 which account for about 70% of cases of cervical cancer; the Merck vaccine also targets HPV6 and HPV11 which account for about 90% of external genital warts. The following summarizes background information relevant to this issue:

• Cervical cancer: 10% of cancers in women
• Developing countries account for 80% of cases due to lack of cancer screening programs – e.g. Pap smear
• Oncogenic HPV types: total is 15, HPV16 accounts for 50%; HPV18 accounts for 20%
• Prevalence of HPV infection: 20-40% of sexually active 20 year old; lifetime risk 75%
• Most important risk for high grade dysplasia: infection with HPV16 or HPV18 that persists > 6 months
• The interval between infection and malignant progression take > 10 years

The following table summarizes four clinical trials with these new vaccines:

*Values for controls/vaccine recipients
** 1. Koutsky LA, et al N Engl J Med 2002;347;1645
     2. Harper DM et al. Lancet 2004;364;1757
     3. Villa LL, et al. Lancet Oncol 2005;107;18
     4. Mao C, et al. Obstet Gynec 2006;107;18

In terms of impact, the short term outcome in industrialized countries such as the US would be an anticipated reduction in the number of CIN2 cases by about 1/3 to 1/2 for vaccinated women compared to those without the vaccine.  This would reduce medical and psychological morbidity in the short run and reduce the incidence of cervical cancer in the long run.  For the developing countries which account for 80% of cervical cancers, the potential is to save several hundred thousand cancers annually, but there would be a substantial lag before this benefit would be realized and the authors consider that vaccination in low-resource settings would be considered cost-effective only if the expense of the vaccine was modest. 

Literature Review by John G. Barlett, M.D. Professor, Division of Infectious Diseases

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