Vaccine shows promise in preventing cervical cancer

Follow-up shows 100% effectiveness rate

An investigational vaccine has reduced the incidence of both human papillomavirus type 16 (HPV-16) infection and HPV-16-related cervical intraepithelial neoplasia (pre-cancer of the cervix), according to research published in the Nov. 21, 2002, issue of the New England Journal of Medicine.

In the double-blind study, none of the women who were vaccinated and had not been previously infected with HPV-16 became infected, whereas 3.8% of those who were not vaccinated developed HPV infection each year. "Immuniz-ing HPV-16-negative women [with the vaccine] may reduce their risk of cervical cancer," the researchers concluded.

HPV-16 is the most common type of HPV linked to cancer; it is present in 50% of cervical cancers and high-grade cervical intraepithelial neoplasias and in 25% of low-grade cervical intraepithelial neoplasias. The monovalent vaccine, intended to prevent infection by HPV-16, contains virus-like particles that are devoid of DNA and are not infectious. However, they still generate a potent immune response.

To study the vaccine, researchers included 1,533 women ages 16-23 in the primary analysis. The women were not pregnant, reported no prior abnormal Pap smears, and reported that they had had no more than five male sex partners during their lifetime. They were randomly given either three doses of placebo or the HPV-16 vaccine, at day 0, month 2, and month 6.

The primary endpoint was persistent HPV-16 infection, defined as the detection of HPV-16 DNA in samples with use of polymerase chain reaction. At least 31 cases of persistent HPV-16 infection were required for the study to show a statistically significant reduction in the primary endpoint. This occurred at about two years into the study. The women will continue to be followed for a total of four years.

The women were followed for a median of 17.4 months after completing the vaccination regimen. All 41 cases of HPV-16 infection, including nine cases of HPV-16-related cervical intraepithelial neoplasia, occurred in the placebo group.

An accompanying editorial in the New England Journal of Medicine praised the research. "Five HPVs — types 16, 18, 31, 33, and 45 — are responsible for most cervical cancers. If women were vaccinated against these types of HPV before they became sexually active, there should be a reduction of at least 85% in the risk of cancer and a decline of 44% to 70% in the frequency of abnormal Papanicolaou smears attributable to HPV. Because the more pernicious cancers appear most often with HPV-16 and HPV-18, the level of protection from death due to cervical cancer could exceed 95%," says Christopher P. Crum, MD, director of women’s and perinatal pathology division at Brigham and Women’s Hospital in Boston.

An advance such as an effective vaccine against HPV could have profound results on the current standard of care, he continues. "If the promise implicit in the study by Koutsky et al is realized, we could, in our lifetime, see the gradual but progressive dismantling of the barriers to preventing cervical cancer. The captives of our current system — both patients and their caregivers — may be set free."

Merck Research Laboratories, which manufactures the vaccine, funded the research and also has financially supported some of the researchers.