HPV vaccine may be of value for women already exposed to some HPV strains

Women who are already infected with some of the four strains of human papilloma virus (HPV) that Gardasil protects against are protected by the vaccine against pre-cancerous or cancerous cervical cell changes caused by the remaining cancer-causing strains, according to research published in the November 15^th edition of the Journal of Infectious Diseases. The study also showed that the vaccine was highly effective at preventing anogenital and vaginal lesions caused by the remaining strains.

Gardasil is a vaccine against HPV-6, -12, -16 and -18, all of which are associated with cancerous and pre-cancerous cell changes in the cervix (and anus). Clinical trials have shown that it is highly effective at preventing cervical and genital HPV-related disease in women who are uninfected with these strains of HPV.

However, many sexually active women will already be infected with one or more of these four HPV strains and investigators wished to determine the efficacy of the vaccine at preventing disease caused by the remaining strain or strains.

The investigators analysed the results from two clinical trials (the FUTURE I and FUTURE II studies) into the safety and efficacy of the vaccine. The trials were placebo-controlled and enrolled 17,622 women. The investigators restricted their current analysis to women who were infected with between one and four of the HPV strains that Gardasil is designed to protect against.

A total of 4,722 (2,368 of whom received Garadasil, the rest a placebo) women were infected with one or more of the strains that Gardasil protects against and were included in the investigators’ analysis. Patients had a mean age of 20 years, the mean age of sexual debut was 16.5 years, and mean number of lifetime sexual partners was two.

Amongst women infected with between one or three strains of HPV that the vaccine protects against, Gardasil was 100% effective at preventing pre-cancerous or cancerous cervical cell changes caused by the remaining strain(s). Over three years, the efficacy of the vaccine at preventing pre-cancerous or cancerous cervical cell changes due to the remaining strains was 91%.

Furthermore, the vaccine had a 94% efficacy at preventing anogenital and vaginal lesions caused by the strain(s) of HPV with which the women were uninfected.

Side-effects, such as headache, fever, sore throat and nausea occurred with equal frequency in the vaccine and placebo arms.

“The analysis provided here demonstrates that women who are infected with HPV-6, -11, 16, or -18 benefit from administration of the quadrivalent HPV (types 6, 11, 16, 18)…vaccine because they are protected from infections and disease caused by HPV types for which they are naïve at the start of vaccination”, write the investigators, “this benefit is important because the incidence of new HPV infections among such subjects is higher than that among women who are naïve for all four HPV vaccine types…the quadrivalent HPV vaccine to these previously exposed individuals was generally well tolerated.”

So far HPV vaccination strategies have been focused on girls in their pre-teens or very early teens who are unlikely to be sexually active and are therefore unexposed to HPV. However, the study investigators believe that their results show that vaccinating older, sexually experienced girls and young women could be of some value. Study investigator Daron Ferris commented, “these findings confirm that girls and young women already exposed to some virus types afforded protection by the four-type virus will still benefit from vaccination. They will be protected against disease, including cervical cancer, caused by other [HPV] types targeted by the vaccine.”

However, the findings of the study do not demonstrate that the vaccine protects against pre-cancerous and cancerous changes caused by HPV types not included in the vaccine among women who had already acquired one or more of those HPV `oncotypes` by the time they entered the study. Research in sub-Saharan Africa has shown a high prevalence of these oncotypes in women, particularly among those with HIV. Further research will be needed to demonstrate a protective effect in this group of women.

There is currently no evidence to show the safety and efficacy of Gardasil in boys or men or in men and women with HIV, although studies in these populations are currently underway.