Two Doses of HPV Vaccine May Protect as Much as Standard 3-dose Course

Two doses of the human papillomavirus (HPV) vaccine Cervarix were as effective as the current standard three-dose regimen after four years of follow-up, according to researchers from the National Cancer Institute (NCI), part of the National Institutes of Health, and their colleagues. The results of the study, based on data from a community-based clinical trial of Cervarix in Costa Rica, appeared online Sept.9, 2011, in the Journal of the National Cancer Institute.

Worldwide, approximately 500,000 new cases of cervical cancer are diagnosed every year, and about 250,000 women die from the disease. An overwhelming majority of these new cases and deaths occur in low-resource countries. Virtually all cases of cervical cancer are caused by persistent infection with HPV. Cervarix is one of two vaccines approved by the U.S. Food and Drug Administration to protect against persistent infection with two carcinogenic HPV types, 16 and 18, which together account for 70 percent of all cervical cancer cases. The vaccine is intended to be administered in three doses given over the course of six months. To date, investigators have observed up to eight years of protection from persistent HPV infection with the vaccine. Studies are ongoing to determine the maximum length of protection.

The cost of the vaccine as well as the logistical difficulties of administering three doses to an adolescent population in resource-poor countries is greater than administering two doses. Even in wealthier countries such as the United States, few adolescent females complete the entire course of three vaccinations. According the Centers for Disease Control and Prevention, although approximately 49 percent of American girls ages 13 to 17 received one dose of the vaccine in 2010, only 32 percent received all three doses. In the United States, the predominately used HPV vaccine is Gardasil, which has a different formulation than Cervarix. Gardasil also protects against up to 90 percent of genital warts because it targets HPV strains 6 and 11 as well as 16 and 18.

The NCI-sponsored Costa Rica Vaccine Trial was designed to assess the efficacy of Cervarix in a community-based setting. Women ages 18 to 25 years were randomly assigned to receive the HPV vaccine or a Hepatitis A vaccine as the control treatment. Although the investigators intended to administer all three doses of the assigned vaccine to all 7,466 women in the study, about 20 percent of the participants received only one or two doses of the HPV or control vaccine. A third of women did not complete the vaccine series because they became pregnant or were found to have possible cervical abnormalities, reasons that would not likely bias the findings.

The investigators found that, after four years of follow up, two doses of the vaccine conferred the same strong protection against persistent infection with HPV 16 and 18 as did the full three-dose regimen. From just a single dose, they also observed a high level of protection, but they are cautious about the long-term efficacy of a single dose because other vaccines of this type usually require a booster dose. Additional studies are needed to evaluate the efficacy of a single dose, as well as the duration of protection for both one and two doses.

“Our study provides evidence that an HPV vaccine program using two doses will work. It may be that vaccinating more women, with fewer doses for each, will reduce cervical cancer incidence more than a standard three-dose program that vaccinates fewer women,” said Aimée R. Kreimer, Ph.D., lead author and investigator in NCI’s Division of Cancer Epidemiology and Genetics. “The main question will be whether the duration of protection from fewer doses is adequate.”

Kreimer emphasized that findings from this study of the Cervarix vaccine in women in Costa Rica may not be relevant for all populations, such as those in which HIV infection, malnutrition, or endemic diseases may influence the immune response. In addition, it is not known whether the same results would be obtained with the other FDA-approved HPV vaccine, Gardasil, because the vaccine formulations are different.

“Further studies are needed to confirm our findings in other populations as well as to quantify the duration of protection for fewer than three doses,” said Kreimer. “If other studies confirm that fewer than three doses provide adequate protection against persistent cervical HPV 16 and 18 infection, we may be one step closer to prevention of cervical cancer, especially for women in resource-poor settings, where the need is greatest.”

It is important to note that regulatory agencies have approved the HPV vaccine based on prevention of cervical precancers, not persistent infections. From studying the natural history of HPV and cervical cancer, experts know that persistent infections are first steps toward precancer. Furthermore, vaccine recommendations take into consideration many factors and studies. In the United States, the CDC’s Advisory Committee on Immunization Practices determines federal recommendations regarding vaccination.

This study was carried out by an international team of experts from the NCI, the Costa Rica HPV Vaccine Trial, and colleagues at DDL Diagnostic Laboratory in the Netherlands.


Source: NIH

Stress May Increase HPV and Cervical Cancer Risk

Sress can reduce the immune system’s ability to resist HPV, a common sexually transmitted disease that may lead to cancer, according to a recent study published in the Annals of Behavioral Medicine. No such association is seen, however, between past major life events, such as divorce or job loss, and the body’s response to the infection.

"HPV infection alone is not sufficient to cause cervical cancer," explained Fox Chase Cancer Center’s Carolyn Y. Fang, Ph.D. "Most HPV infections in healthy women will disappear spontaneously over time. Only a small percentage will progress to become precancerous cervical lesions or cancer."

Women with precancerous cervical lesions were asked to complete a questionnaire detailing their stress in the past month, such as divorced, death of a close family member or job loss. "We were surprised to discover no significant association between the occurrence of major stressful life events and immune response to HPV16. This could be due to the amount of time that has passed since the event occurred and how individuals assess and cope with the event," said Fang.

"Our findings about subjective daily stress told a different story, however. Women with higher levels of perceived stress were more likely to have an impaired immune response to HPV16. That means women who report feeling more stressed could be at greater risk of events that had occurred, such as divorce, death of a close family member or loss of a job.

"We were surprised to discover no significant association between the occurrence of major stressful life events and immune response to HPV16. This could be due to the amount of time that has passed since the event occurred and how individuals assess and cope with the event," said Fang. "Our findings about subjective daily stress told a different story, however. Women with higher levels of perceived stress were more likely to have an impaired immune response to HPV16. That means women who report feeling more stressed could be at greater risk of developing cervical cancer because their immune system can’t fight off one of the most common viruses that causes it."

Fang’s study was funded by a grant from the National Cancer Institute.


Source: Annals of Behavioral Medicine (Vol. 17, No. 1)

HPV Vaccine Not Effective for Treating Genital Warts in Women

For women with human papillomavirus (HPV) infection, use of the HPV-16/18 vaccine will not accelerate reduction of the virus and should not be used to treat the infection, according to a study in the August 15, 2007 issue of JAMA.

HPV vaccines were designed to prevent HPV infection and the development of cervical precancers and cancer. Some research has suggested that HPV vaccines could help clear the virus in women already infected, according to background information in the article.

Allan Hildesheim, Ph.D., of the National Cancer Institute, Bethesda, Md., and colleagues conducted a study to address the question of whether women positive for HPV DNA should be encouraged to receive HPV-16/18 vaccination to induce or accelerate clearance of their infections. The trial was conducted in two provinces of Costa Rica and included 2,189 women age 18 to 25 years who were positive for HPV DNA. Participants were randomly assigned to receive three doses of HPV-16/18 vaccine (n = 1,088) or a control hepatitis A vaccine (n = 1,101) over 6 months.

There was no evidence that HPV vaccination significantly altered rates of viral clearance. At the 6-month visit, rates of clearance were 33.4 percent vs. 31.6 percent for HPV-16/18 among participants who received the HPV vaccine and the control vaccine, respectively. At the 12-month visit, rates of clearance among participants in the HPV group and the control group, respectively, were 48.8 percent vs. 49.8 percent for HPV-16/18.

There was no evidence of vaccine effects with further analysis on selected study entry characteristics reflective of disease extent, including HPV-16/18 antibody results, cytologic results, and HPV viral load. Similarly, no evidence of vaccine effects was observed in analyses stratified by other study entry parameters thought to potentially influence clearance rates and efficacy of the vaccine, including time since sexual initiation, oral contraceptive use, cigarette smoking, and concomitant infection with Chlamydia trachomatis or Neisseria gonorrhoeae.

"These findings have important clinical implications. For example, in countries where HPV DNA testing is incorporated in cervical cancer screening and prevention efforts, adult women who have abnormal Papanicolaou test results induced by HPV infection and/or who test positive for an oncogenic HPV type using the clinically available HC2 test might be interested in receiving the HPV vaccine to treat their existent infection," the authors write. "…our results demonstrate that in women positive for HPV DNA, HPV-16/18 vaccination does not accelerate clearance of the virus and should not be used for purposes of treating prevalent infections."


Source: JAMA. 2007;298(7):743-753.