May 26, 2009

HPV Vaccine More Potent Than Expected

It turns out that Gardasil, the vaccine that protects against wart- and cancer-causing human papillomavirus (HPV), may be even more potent than originally thought. New research suggests it protects women against multiple HPV strains, not just the original four it was developed to target.

Long-term data from studies involving more than 17,000 women offer more good news about Gardasil, the vaccine against human papillomavirus (HPV)—a virus that can cause cervical, anal and penile cancer as well as genital warts. According to a study presented at the International Papillomavirus Conference in Malmö, Sweden, in early May, Gardasil doesn’t just protect women from the four strains of HPV targeted by the vaccine, it may also defend against precancerous cervical lesions caused by other strains of the virus.

This is a welcome announcement not only for women in general, but also for women living with HIV and men who have sex with men (MSM). Women with HIV are at much higher risk than HIV-negative women for infection with HPV and developing cervical cancer; MSM, notably HIV-positive men, are believed to face a heightened risk of anal HPV infection and cancer. Though many HIV-positive women and MSM are already infected with the strains of HPV targeted by Gardasil, vaccination could be tremendously helpful for those who are not.

The Road to Protection

Gardasil was initially tested in more than 20,000 HIV-negative women; it was found to offer nearly 100 percent protection against two cancer-causing HPV strains, types 16 and 18, and two other strains, types 6 and 11, often associated with genital warts. Some scientists, however, have worried that claims of nearly 100 percent efficacy have led people to assume that Gardasil completely protects against cervical cancer from all of the various strains of HPV that have been linked to cervical cancer. The data presented at the time of Gardasil’s approval, they argue, simply didn’t go on long enough to prove the vaccine’s long-term efficacy, nor did the research include lesions caused by other HPV strains, such as types 31 and 45.

Now, a long-term analysis of 17,622 women from the two large Phase III studies used to approve the vaccine has shown that Gardasil may in fact offer significant protection against precancerous lesions caused by strains of HPV other than those targeted by the vaccine, a concept known as cross-protection. Though additional studies will be needed to draw any conclusions, these initial observations are encouraging.

Parsing the Data

Jorma Paavonen, MD, from the University of Helsinki in Finland, and his colleagues from the Quadrivalent HPV Vaccine Phase III Study compared the vaccine to a placebo in roughly 8,000 women with a history of HPV infection and just over 9,000 who had never been infected with any of the four main strains of HPV targeted by Gardasil. He and his colleagues were interested to learn whether the vaccine protected women from strains of HPV other than types 16 and 18.

In an analysis of the women with no history of HPV infection, Gardasil performed as expected. Over the past three and a half years, 48 women who received the placebo developed the most serious type of precancerous lesions: cervical intraepithelial neoplasia grade 2 or 3 (CIN2+) due only to infection with HPV types 16 or 18. Among those who received the vaccine, no cases of CIN2+ caused by HPV 16 or 18 were reported.

Of particular interest to Paavonen are data suggesting that Gardasil might also offer protection against HPV types not targeted by the vaccine. His group isolated HPV types other than 16 and 18 in CIN2+ lesions in 57 women on Gardasil, compared with 79 women who got the placebo. This, Paavonen suggests, represents a 28 percent reduction in the risk of CIN2+ from all strains of HPV, not just types 16 and 18.

There is an important caveat, however. Twenty six of the 79 women in the placebo group with CIN2+ were coinfected with HPV type 16 or 18 and other strains of HPV known to cause precancerous lesions. As it is possible HPV types 16 or 18 contributed to the development of CIN2+ in these women, it is impossible to conclude with certainty that Gardasil is necessarily more effective at protecting against precancerous lesions caused by non-16 or -18 types of HPV. Further exploration of these findings is necessary.  

Paavonen points out, however, that it’s not just the number of precancerous lesions that dropped, but also the invasive and uncomfortable procedures used to diagnose and treat those lesions. The need for cervical biopsies dropped by 22 percent, and the need for treatment of cervical lesions decreased by 42 percent. Paavonen says such procedures not only cause women discomfort and emotional distress, but also increase medical costs. The reduction in invasive procedures, he says, will have a significant public health impact.

Hope for Others

Though Paavonen’s analysis cannot be extrapolated to HIV-positive women or MSM, it is hoped that the vaccine will be efficacious for them as well. The AIDS Clinical Trials Group (ACTG) is in the middle of a study exploring whether the vaccine is safe in HIV-positive women and whether it causes the women to develop antibodies to the strains of HPV that the vaccine targets. If HIV-positive women are able to mount an antibody response that is comparable to HIV-negative women, larger efficacy trials are likely to be conducted.

Similarly, Gardasil is being tested in young men, both heterosexual men and MSM. Interim results suggest the vaccine reduces the persistence of anal and genital warts and precancerous anal lesions by at least 85 percent. Merck has applied to the FDA for approval of the vaccine in young men and is awaiting an answer while also following the men in the trial for a longer period. Thus far, there are no studies ongoing in HIV-positive men, though some researchers have proposed that if the vaccine is proved effective in HIV-negative men it should be offered to HIV-positive men as well.

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Previous Comments:

Wes Meekins, San Diego, 2009-05-28 10:06:06
I certainly hope this Gardasil becomes available soon, unfortunately I am one of these people with a situation of anal warts, not bad but can be corrected with this medication! Please FDA get your act together on these procedures and treatments to help lower our health costs and improve our lives. I am 48 living with HIV who knows what the future clock holds for me?? Please Help! Wes San Diego

Positive in San Diego, San Diego, 2009-05-27 16:10:51
I was vaccinated with Gardasil almost two years ago because I told my doctor that if he wouldn't give it to me, I'd go down to Tijuana and buy it there. He administered it, but my insurance company charged me $700. Well worth it in my opinion, since the mortality rate for HIV at least in my clinic's caseload has been 75% due to HPV-related anal cancer. I think any MSMs who are positive would be best served by getting the vaccine, with our without FDA approval.

Randy, San Jose, 2009-05-27 12:33:20
I know this is wishful thinking and Im way ahead of thses studdies, but as a person who had anal cancer can this vaccine be helpful to me?

Dr. Richard S. Ferri, Brewster, 2009-05-27 10:42:17
This vaccine so needs to be "fast tracked" for men. I see way too many men in practice barebacking and developing anal cancers. We need to deal with this fact, and the issue of "safe sex" being a thing of the past.