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Human papillomavirus (HPV) vaccine research focuses on the prevention and treatment of diseases, such as cervical cancer and genital warts, caused by sexually transmitted human papillomaviruses.

In 2006, the U.S. Food and Drug Administration approved the first preventive HPV vaccine, marketed by Merck & Co. under the tradename Gardasil.

GlaxoSmithKline is expected to seek approval for a similar preventive HPV vaccine, known as Cervarix, early in 2007.

Introduction

Of the more than 120 known HPV types, about 30 are adapted to be transmitted through sexual contact. Infection with sexually-transmitted HPVs is very common in adult populations worldwide. Although a few HPVs, such as types 6 and 11, can cause genital warts, most genital HPV infections come and go without ever causing any symptoms. However, lingering infections with a subset of about a dozen "high-risk" HPV types, can lead to the development of cervical cancer or other genital/anal cancers.

The current generation of preventive HPV vaccines are based on hollow virus-like particles (VLPs) assembled from recombinant HPV coat proteins. The vaccines target the two most common high-risk HPVs, types 16 and 18. Together, these two HPV types cause about 70 percent of all cervical cancer. Gardasil also targets HPV types 6 and 11, which together cause about 90 percent of all cases of genital warts.

Gardasil and Cervarix are designed to elicit virus-neutralizing antibody responses that prevent initial infection with the HPV types represented in the vaccine. The vaccines have been shown to offer 100 percent protection against the development of cervical pre-cancers and genital warts caused by the HPV types in the vaccine, with few or no side effects. The protective effects of the vaccine are expected to last a minimum of 4.5 years after the initial vaccination.

While the study period was not long enough for cervical cancer to develop, the prevention of these cervical precancerous lesions (or dysplasias) is believed highly likely to result in the prevention of those cancers.

Although a 2006 study suggests that the vaccines may offer limited protection against a few HPV types that are closely related to HPVs 16 and 18, it is clear that other high-risk HPV types can circumvent the vaccines. Ongoing laboratory research is focused on the development of HPV vaccines that will offer protection against a broader range of HPV types. There is also substantial research interest in the development of therapeutic vaccines, which seek to elicit immune responses against established HPV infections and HPV-induced cancers.

Target populations

It is important to note that Gardasil and Cervarix are preventive (rather than therapeutic) vaccines and are not expected to benefit women who are already infected. For this reason, the US Centers for Disease Control and Prevention has recommended vaccination of girls as young as nine years old. Sexually-transmitted HPVs are highly contagious, and epidemiological studies have demonstrated a major spike in the incidence of initial HPV infection during adolescence.

Although HPV types 6 and 11 do not cause cervical cancer, they can cause genital warts. "Warts cause considerable discomfort and psycho-social trauma, so this makes the vaccine more attractive and also provides a reason other than altruism for men to be immunized," explains John Schiller of the National Cancer Institute.

Implementation

In developed countries, the widespread use of cervical "Pap smear" cancer screening has dramatically reduced the incidence of invasive cervical cancer. Since the current generation of preventive vaccines will not protect against all the HPV types that can cause cervical cancer, it will be important for women to continue to seek regular Pap smear screening, even after vaccination.

Pap smear screening is too expensive for routine use in developing countries and HPV-induced cervical cancer remains the second most common cancer in women worldwide. Thus HPV vaccines are most urgently needed in developing countries. With a cost of $360, Gardasil is the most expensive vaccine ever developed. The vaccine will be too expensive for initial use in developing countries unless substantial subsidies are offered. Merck has announced that it intends to support programs to offer Gardasil to disadvantaged women worldwide . The Bill & Melinda Gates Foundation has also expressed interest in helping make preventive HPV vaccines available to women in developing countries.

Intellectual history of HPV vaccines

The key initial discoveries leading to development of preventive HPV vaccines stemmed from government-funded basic science research sponsored by the United States, Australia and Germany. For a brief history of the development of HPV VLP technologies, see articles entitled "Who Invented the VLP Cervical Cancer Vaccines?" in the Journal of the National Cancer Institute and "How A Vaccine Search Ended In Triumph" (New York Times, August 29, 2006; external link below).

Controversy

A few conservative religious groups publicly oppose the concept of making HPV vaccination mandatory for pre-adolescent girls, citing fears that vaccination against a sexually-transmitted disease might send a subtle message condoning pre-marital sex.

Therapeutic HPV vaccines

In addition to preventive vaccines, such as Gardasil and Cervarix, laboratory research and several human clinical trials are focused on the development of therapeutic HPV vaccines. In general these vaccines focus on the main HPV oncogenes, E6 and E7. Since expression of E6 and E7 is required for promoting the growth of cervical cancer cells (and cells within warts), it is hoped that immune responses against the two oncogenes might eradicate established tumors .

References

1. MacLachlan Kathleen (2006). "Human Papillomavirus Infection in the College Age Population". collegehealth-e. 1 (4): 2–7.fulltext pdf}}
2. ^ Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trialLancet. 2006 Apr 15;367(9518):1247-55
3. FDA Licenses New Vaccine for Prevention of Cervical Cancer and Other Diseases in Females Caused by Human PapillomavirusFDA press release
4. HPV vaccine moves into late stage trials, Nature Medicine 7, 388 (2001), accessed May 19, 2006
5. FDA Approves Merck's GARDASIL®, the World's First and Only Cervical Cancer Vaccine (Merck press release)
6. Who Invented the VLP Cervical Cancer Vaccines? McNeil, C., Journal of the National Cancer Institute, 2006, 98(7): 433.
7. Pro-Family, Pro-Vaccine -- But Keep It Voluntary Sprigg, P., The Washington Post
8. Vaccination to prevent and treat cervical cancerHum Pathol. 2004 Aug;35(8):971

External links

• Defusing the War Over the "Promiscuity" Vaccine, TIME Magazine, June 21, 2006
• Women’s Health Specialists Welcome Cancer Prevention Vaccine - July 18, 2006
• Health Politics: HPV Vaccine
• Panel Unanimously Recommends Cervical Cancer Vaccine for Girls 11 and Up -- The New York Times
• How a Vaccine Search Ended in Triumph -- The New York Times

• Vaccines