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

Herpes Prevalent in 16 Percent of Americans Aged 14-49

About 1 in 6 Americans (16.2 percent) between the ages of 14 and 49 is infected with herpes simplex virus type 2 (HSV-2), according to a national health survey released today by the Centers for Disease Control and Prevention.  HSV-2 is a lifelong and incurable infection that can cause recurrent and painful genital sores.

The findings, presented at the 2010 National STD Prevention Conference, indicate that herpes remains one of the most common sexually transmitted diseases (STDs) in the United States.

The new estimate, for 2005-2008, comes from CDC’s National Health and Nutrition Examination Survey (NHANES), a nationally representative survey of the U.S. household population that assesses a broad range of health issues.

The findings suggest relatively stable HSV-2 prevalence since CDC’s last national estimate (17 percent for 1999-2004), because the slight decline in prevalence between the two time periods is not statistically significant.

The study finds that women and blacks were most likely to be infected.  HSV-2 prevalence was nearly twice as high among women (20.9 percent) than men (11.5 percent), and was more than three times higher among blacks (39.2 percent) than whites (12.3 percent).  The most affected group was black women, with a prevalence rate of 48 percent.

As with other STDs, biological factors may make women more susceptible to HSV-2 infection. Additionally, racial disparities in HSV-2 infection are likely perpetuated because of the higher prevalence of infection within African-American communities, placing African-Americans at greater risk of being exposed to herpes with any given sexual encounter.

“This study serves as a stark reminder that herpes remains a common and serious health threat in the United States.  Everyone should be aware of the symptoms, risk factors, and steps that can be taken to prevent the spread of this lifelong and incurable infection,” said Kevin Fenton, M.D., director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.  “We are particularly concerned about persistent high rates of herpes among African-Americans, which is likely contributing to disproportionate rates of HIV in the black community.”

Research shows that people with herpes are two to three times more likely to acquire HIV, and that herpes can also make HIV-infected individuals more likely to transmit HIV to others.  CDC estimates that over 80 percent of those with HSV-2 are unaware of their infection.  Symptoms may be absent, mild, or mistaken for another condition.  And people with HSV-2 can transmit the virus even when they have no visible sores or other symptoms.

“Many individuals are transmitting herpes to others without even knowing it,” said John M. Douglas, Jr., M.D., director of CDC’s Division of STD Prevention.  “We can’t afford to be complacent about this disease.  It is important that persons with symptoms suggestive of herpes—especially recurrent sores in the genital area—seek clinical care to determine if these symptoms may be due to herpes and might benefit from treatment.”

Combination of Prevention Approaches Needed to Reduce National Herpes Rates
Although HSV-2 infection is not curable, there are effective medications available to treat symptoms and prevent outbreaks.  Those with known herpes infection should avoid sex when herpes symptoms or sores are present and understand that HSV-2 can still be transmitted when sores are not present. Effective strategies to reduce the risk of HSV-2 infection include abstaining from sexual contact, using condoms consistently and correctly, and limiting the number of sex partners.

CDC does not recommend HSV-2 screening for the general population.   However, such testing may be useful for individuals who are unsure of their status and at high risk for the disease, including those with multiple sex partners, those who are HIV-positive, and gay and bisexual men.


Source: Centers for Disease Control (CDC), March 9, 2010