Dear Dr. Poyner,

I am 45 years old and newly single.  This dating scene is alarming enough without considering the risk of HPV and cancer that I hear so much about in the media.  I have never had an abnormal pap smear and have had only 4 sexual partners in my life, the last one for 20 years.

I am smart enough to choose a partner carefully and to insist on condom use.  I have heard that even condoms won’t protect me from HPV exposure.  What can I do to limit my exposure to this disease?  My gynecologist told me that I was too old to get that vaccine against HPV.  Can you explain this to me?

Betsy

Dear Betsy,

Before we get to your core question, let’s look overall at what HPV really is.

The  human papilloma viruses, referred to as HPV, are a group of over 100 related viruses and each HPV virus in the group is given a number, which is called an HPV type. Sixty HPV types cause common warts on non-genital skin, such as on the hands and feet.  The 40 other types infect mucosal areas of the body; these are referred to the “genital HPV types”, which infect the male and female genital regions.

These latter types of HPV are responsible for genital warts, also referred to as condyloma acuminatum, — dysplasia (or precancers) of the cervix and other external genital structures (labia, perineum, and vagina),  most often caused by HPV-6 and HPV-11.  Because these genital warts rarely develop into cancer, HPV-6 and HPV-11 are called “low-risk” viruses.  But some other HPV types that affect genital tissues have been linked with cancer, including anal cancer in both men and women. These are called “high-risk” HPV types and include HPV-16 and HPV-18, most commonly.

Genital HPV is transmitted mainly by direct genital contact. It’s most  common soon after a woman becomes sexually active, with and up to 75% of sexually active women have had an HPV infection at some point in their lives.

Usually they’ve had no symptoms, unless the HPV is the type that causes genital warts. Many women will never know that they have been infected with the HPV virus, as the body’s immune system “clears” the virus (either through destruction of the virus or suppression of the virus to undetectable levels). However, some women may harbor the virus for prolonged periods of time and over years may develop cervical, vaginal, vulvar or anal cancers.

There are no reliably demonstrated treatments for HPV, once a woman is infected; therefore prevention of the virus becomes quite important. Because the virus is transmitted through contact with infected skin, condoms are not 100% effective (however they should still be used in order to prevent other sexually transmitted diseases). Prevention strategies include: limiting the number of sexual partners, not having sex with people who have had many partners and getting the HPV vaccine before exposure.

Now on to the vaccine.

In 2006, the Food and Drug Administration (FDA) approved Gardasil, a tetravalent HPV vaccine that prevents two types of HPV (HPV 16 and 18) that cause 70% of all cervical cancers. and prevents two types of HPV (HPV 6 and 11) that cause 90% of all genital warts. Since the vaccine is most effective before exposure to HPV, the initial studies used to FDA approve the vaccine, were composed of young HPV women who had had no sexual contact. The FDA determined that the vaccine is safe and effective for females aged 9 to 26 years and approved the vaccine.

The risk of HPV exposure is highest soon after women become sexually active. Therefore, it is likely that women over 26 have already been exposed to HPV and would not benefit as much from the vaccine. However, all sexually active women are at risk for HPV exposure throughput their lives. Researchers have found that only a few women are infected with all four common HPV types that Gardasil protects against. The theory is that the vaccine would prevent women infected with one or more of the strains from contracting the others. The FDA therefore granted priority review status to Merck’s application to expand marketing of its human papillomavirus vaccine, Gardasil, to women ages 27 to 45.  The FDA however rejected Merck’s application to expand the use of Gardasil in this age group pending more data and information.

A second HPV vaccine submission to the FDA is also in progress, Cervarix, from GlaxoSmithKline (GSK). This is a bivalent vaccine against HPV 16 and 18 that has demonstrated immune responses in older women. GSK said it has decided to wait until results from a Phase III trial of the vaccine are available before seeking U.S. approval. The study results likely will be submitted to FDA in the first half of 2009, with an FDA decision expected no more than six months later.

Some physicians may advocate and use the HPV vaccine “off label”, without demonstration of effectiveness for women over the age of 26. They argue that the immune response should be robust enough.  The doctors who are choosing to use the HPV vaccine off label support report that it is unlikely that an older woman would have had prior exposure to all four common HPV types and therefore would derive some benefit from the vaccine. Other physicians advocate no “off label” vaccinations. As with the administration of any medication or vaccine the benefits should always be weighed against the risks.

Although the HPV vaccine, Gardasil, appears to be very safe some adverse events have been reported and we have overall only a 2 and one half year experience with vaccination of large numbers of women outside of controlled studies. Therefore, although the two HPV vaccines may be promising for older women, they have yet to be approved and we all wait the additional data /information of the effectiveness and safety of these vaccines in women over the age of 26. Up until that time, decisions of vaccination must be made with discussions of the risks and benefits of an “off label” use between women and their treating physicians.