The Human Papilloma Virus (HPV) is one of the most common sexually transmitted infections (STI) in the world, with an estimated 5.5 million people infected annually. Sexually active individuals have an 80 to 85% chance of being infected at some time in their lives. Although it is considered a sexually transmitted disease, it can be spread by skin-to-skin genital contact without intercourse. It is most prevalent in women 20-24 years of age, and prevalence decreases with age, dropping significantly after age 30. It is thought that the younger, developing cervix is more likely to be infected, but these infections tend to be short-lived and are usually cleared by the immune system.
About 20% of women infected with HPV will develop chronic infection, and of these about 2% will develop cervical cancer. Researchers have determined that HPV is found in almost 100% of cervical cancers worldwide. There are an estimated 493,000 cases of cervical cancer and 273,500 deaths each year worldwide. It is less common in the U.S., where Pap smears are routine, with 14,000 new cases and 3,900 deaths each year.
There are about 100 different strains of HPV, 40 of which can infect the anal and genital tissues. Many people think of HPV as the virus that causes genital warts, yet only a few of the 100 strains actually cause warts, and these strains are not the ones that cause cervical cancer. There are 15 strains thought to be “high risk” and able to cause cervical cancer. Strains 16 and 18 are by far the most common types, and one or both are present in approximately 70% of cervical cancers worldwide. Despite this strong link, only a very small percentage of high-risk HPV infections will ever become invasive cancer (estimated at 2%). The time between initial exposure and the development of cancer can vary from months to years, but the average time is thought to be 15 years. Unfortunately, the high-risk HPV strains do not usually cause any symptoms to alert someone that she has the infection. The low-risk strains are not considered a risk for cervical cancer, but they can cause low-grade lesions (CIN 1) and several of these strains can cause genital warts.
There is a lot of talk in the media recently about the new HPV vaccines developed by Merck (Gardasil) and Glaxo Smith Kline (Cervarix). The vaccines are given in a three shot series over six months and will cost between $300-500. They are made of an inactive form of the virus so there is no risk of contracting HPV from the vaccine. The Advisory Committee on Immunization Practices, a group consisting of 15 experts in fields associated with immunization, meets on June 29 th , 2006 to make recommendations on how the vaccine is used (who gets it, is it mandatory, etc.).
OncoLink sat down with Christina Chu, MD, Assistant Professor in the Division of Gynecologic Oncology at the University of Pennsylvania Health System, to get the facts on this new development.
: Dr. Chu, thanks for joining us today. Let's start with the basics of the vaccines. What do they protect against and for whom are they meant?
Dr. Chu: The recently FDA-approved Gardasil vaccine is a vaccine against 4 specific types of the Human Papilloma Virus (Types 6, 11, 16, and 18) that are responsible for the majority of cases of cervical cancer, precancer, and genital warts. The Cervarix vaccine is not yet FDA-approved, but will cover HPV types 16 and 18. HPV types 16 and 18 are implicated in approximately 70% of cervical cancer, and HPV types 6 and 11 are responsible for 90% of genital warts. In addition, HPV types 16 and 18 are responsible for 70% of cases of severe dysplasia of the cervix (CIN3), moderate to severe dysplasia of the vulva and vagina (VIN 2-3, and VAIN 2-3), as well as half of all cases of moderate dysplasia of the cervix (CIN2). Together, these 4 types of HPV virus also cause about 35 to 50% of all low-grade cervical, vaginal, and vulvar dysplasias (CIN 1, VIN 1, VAIN 1).
Merck recently earned FDA-approval for the Gardasil vaccine in girls and young women ages 9 to 26 years. These vaccines are primarily meant as a means to help prevent infection with these four specific types of HPV. I think that the best candidates for this vaccine will be girls who have not yet initiated sexual contact, especially since HPV does not require actual sexual intercourse to be transmitted--skin to skin contact is enough. Also, recent findings from a clinical trial using the Cervarix vaccine formulated with an adjuvant (a substance designed to make a vaccine more effective) showed that girls ages 10-14 who received the vaccine developed helpful immune responses that were twice as high as young women who received the vaccine between ages 15-25. In other words, the vaccine was more effective in causing an immune response when given to the younger women.
: What about women who have already been exposed to HPV or have previously had dysplasia or abnormal Pap smears?
Dr. Chu: These vaccines are primarily designed as preventative measures. While the studies that have been done have included some women with prior exposure to the HPV virus, it is not clear that vaccination is effective as a treatment for women who already have established infections. Keep in mind, however, that currently used tests do not tell us which type of virus and individual may be infected, just that there is evidence of infection with one of 15 or so “high risk” types, which include HPV 16 and 18. Even if a patient has infection with one particular type (6, 11, 16, or 18), treatment may still provide protection against the other strains included in the vaccine.
: The vaccine is given in a three shot series over six months. How soon after receiving it are you protected, and how long will the protection last?
Dr. Chu: So far, clinical trials of both the Gardasil and Cervarix vaccines have shown immune responses reaching high levels as soon as 3 months after the first injection, although the peak of immunity is not reached until about 7 months (one month after the last injection). Current data shows that protection seems to last at least 4 years or so, which is how long the studies have been in progress. Immunity may last longer, but only time and further study will confirm that.
: How effective are the vaccines and are there any risks to them?
Dr. Chu: These vaccines appear to be very effective at preventing cancers and precancers of the cervix, vulva, and vagina that are caused by HPV 16 and 18. In clinical trials, the Gardasil vaccine prevented 100% of high-grade cervical precancers and non-invasive cancers, as well as 100% of all high-grade vulvar and vaginal precancers related to HPV 16 and 18. The vaccine also prevented 99% of genital warts related to HPV 6 or 11. It is important to remember that these vaccines cannot prevent all cancer and precancer, since a number of cases are caused by strains of HPV not covered by these vaccines.
So far, side effects have been mild. No serious adverse reactions have been reported that exceed those experienced by patients given a placebo. In fact, some studies have shown that women receiving placebo vaccinations reported more side effects than those receiving the real vaccine. In general, only 1 in 1000 patients discontinued the vaccines due to side effects. For Gardasil, the most common side effects were reported to be only mild or moderate. Main symptoms were pain (84% for those receiving Gardasil, vs. 75% of those receiving placebo), swelling (25% for Gardasil vs. 16% for placebo), redness at the injection sites (25% Gardasil vs. 18% placebo), fever (10% Gardasil vs. 9% placebo), and itching (3% for both Gardasil and placebo). It also is important to note that these vaccines cannot cause infection with HPV.
: Once a woman receives a HPV vaccine, can she stop having annual Pap smears?
Dr. Chu: At this point, women must continue to have regular screening with Pap tests and exams, since we do not know how long immunity lasts, and since other strains of HPV not covered by the vaccines may cause precancer and cancer.
: Well, it takes two to tango, so what about the boys? Is there a use for the vaccine in men?
Dr. Chu: Currently, the FDA approval for Gardasil is only for girls and young women. While the idea of vaccinating men is attractive in that it may serve to further cut transmission rates, there is unlikely to be much direct benefit for boys and men. HPV 16 and 18 are not generally associated with male genital tract cancers, and heterosexual men rarely develop genital cancers caused by HPV. However, men may someday benefit from vaccination against strains of HPV that cause genital warts.