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

Teen Pregnancy May Be Reduced by Sex Education in Schools, Says Study

Sex education may reduce teen pregnancy without increasing the amount of sexual intercourse among teens, or the incidence of sexually transmitted diseases among them, according to new research.

"It is not harmful to teach teens about birth control in addition to abstinence," said study lead author Pamela Kohler, a program manager at the University of Washington in Seattle.

Which approach will postpone sexual experience? Instruction on birth control, or advice on how to say No. That’s the longstanding debate between sex educators and parents. The findings of a study analyzing the response from 1,719 teens, heterosexual and aged between 15 and 19, and the 2002 national survey, found that one in four teens received abstinence-only education, 9%—primarily those living in rural areas and the poor%—received no sex education at all, while the remaining two-thirds received comprehensive instruction with discussion of birth control.

Predictably, those teens receiving comprehensive sex education were 60% less likely to become pregnant or impregnating someone than those receiving no sex education at all. The one in four teens receiving abstinence-only education were 30% less likely to become pregnant than those receiving no sex education at all, although this number was dismissed as statistically insignificant by the researchers because so few teens fit the categories researchers analyzed.

The findings support comprehensive sex education, Kohler said. "There was no evidence to suggest that abstinence-only education decreased the likelihood of ever having sex or getting pregnant." Don Operario, Ph.D., a professor at Oxford University in England, said the study provides "further compelling evidence" about the value of comprehensive sex education and the "ineffectiveness" of the abstinence-only approach.

Still, the study does not show how educators should implement comprehensive sex education in the classroom, said Operario, who studies sex education. "We need a better understanding of the most effective ways of delivering this type of education in order to maximize audience comprehension and community acceptability."


The study appeared in the April, 2008 issue of the Journal of Adolescent Health.

Concerns Voiced Over Long-Term Effects of Synthetic Progestins

In a study done at the University of Oregon, the widely used synthetic progestin medroxyprogesterone acetate (MPA) decreased endothelial function in premenopausal women. The finding, researchers said, raises concerns about the long-term effects of MPA and possibly other synthetic hormones on vascular health in young women.

The vascular endothelium lines the inside of blood vessels. In recent years, it has been found to be a dynamic organ that serves an important role in the prevention of atherosclerosis. "The logical conclusion of this study is that over a long period of time it would not be good to have exposure to an agent that is reducing blood vessel flexibility, because it could be associated with the development of heart disease or related problems," said co-author Dr. Paul F. Kaplan, a long-time Eugene gynecologist and senior researcher in the UO’s human physiology department. He stressed, however, that a longer, larger study is needed.

MPA is the active ingredient of Provera, used to treat abnormal uterine bleeding, induce menstrual cycles and relieve symptoms of menopause. Depo/Provera, an injectible long-lasting contraceptive in common use by many young women, contains MPA as an active ingredient. MPA was also used in the Women’s Health Initiative (WHI) including a clinical study on hormone replacement. This was stopped because of health concerns in post menopausal women. Millions of women use hormone therapies with a variety of progestin types for contraception.

The UO study is among the first to target the impact of MPA in premenopausal women. Fourteen women, 19-27 years old, participated in the study after exams to screen out various health conditions. The five-member UO team—led by Jessica R. Meendering, a former UO doctoral student now a professor of exercise science at the University of Nebraska in Omaha—studied the effects of the sex hormone estradiol by itself and in combination with MPA on endothelial function of the brachial artery. The health of the endothelium in this artery has been shown to be a telling proxy for the coronary arteries and a good predictor of cardiovascular risk.

When researchers gave an oral version of MPA to determine its impact, they found that it wiped out the positive effects on endothelial function that estradiol had provided. MPA reduced the function by reducing the brachial artery’s ability to dilate—grow bigger in diameter—in response to the stress of changing blood flow, Kaplan said.

Source: Journal of Physiology: Heart and Circulatory Physiology

Researchers Find that Head and Neck Cancers May Be Different Diseases

Different risk factors for head and neck cancer have been identified by researchers at Johns Hopkins Kimmel Cancer Center, raising the possibility that they are different forms of these diseases.

Head and neck tumors caused by the human papillomavirus (HPV) were generally associated with sexual behaviors and smoking marijuana, rather than tobacco and alcohol. It was also found that people with the viral-linked cancer were mostly white, younger, married, and college-educated with income of $50,000 or more. Those not attributable to HPV were associated with tobacco, alcohol and poor oral hygiene, most generally listed as the causes of head and neck cancer. The findings are to be published in the March 12 issue of the Journal of the National Cancer Institute.

"Our results indicate that HPV-positive and HPV-negative head and neck cancers have different risk-factor profiles and should be considered two distinct diseases," says Maura L. Gillison, M.D., Ph.D., an associate professor of oncology and epidemiology at Hopkins. "They just happen to occur in the same place."

HPV infection has been seen in up to 72% of patients, and is associated with the development of some neck and head cancers, mostly in the upper throat and back of the tongue. Gillison noted that the incidence of HPV-linked cancer has nearly doubled over the past 30 years, and that head and neck cancer patients with HPV-positive tumors are mlore responsive to treatment and survive longer than HPV-negative patients.

According to Gillison, the American Joint Committee on Cancer is now considering incorporating HPV status in its guidelines for determining clinical stages of head and neck cancer.

For this study, 240 patients at the Johns Hopkins Hospital with head and neck squamous cell carcinomas were studied between 2000 and 2006, to identify HPV-positive or negative tumors. All study participants completed a computerized interview that asked questions about their risk factors.

Source: Journal of the National Cancer Institute, March 12, 2008

Experts Say Future Generations Will Experience Increased Infertility

Commenting on infertility, experts from the Aarhus University Hospital, Denmark and the University of California observe that infertility is a common problem in affluent societies, and it affects some 15% of couples who are trying to conceive.

Assisted reproductive methods are used in some countries to conceive up to 6% of children. But fertility is determined by social, behavioral and biological factors, say the authors, which could make studies based on retrospectively collected data unreliable. These cultural and social norms may mask more subtle biological changes in the population, and representative health surveys should include fecundity.

Fecundity is expected to decline over time, the study’s authors predict, because with the availability of assisted conception subfertile couples may have as many children as fertile couples. Genetic factors linked to infertility will become more prevalent in the future. Meanwhile, dealing with the causes of subfecundity, say the authors, is the best way to fight infertility, and neglected research should be undertaken without delay.

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)

Vaccination Controversy Spills Over to Video Sharing Site YouTube

There is a growing debate over the necessity of the number of vaccines administered today. The controversy often surrounds a number of issues, such as pharmaceutical company lobbying to require administration of vaccinations that critics say have not undergone adequate testing.

For example, many states have pending bills that would require young girls to be vaccinated against HPV with Merck’s Gardasil. Currently only Virginia has passed a bill, as controversy has stalled bills in other states. The Virginia bill requires girls entering the sixth grade to be vaccinated, though it allows parents to opt their daughters out.

In February, 2007, Merck & Co. discontinued its lobbying of state
legislatures in an attempt to make it mandatory for girls to be inoculated with
Gardasil.

Others argue that over-vaccination will have long term detrimental effects on human immune systems. In the Journal Immunology Today researchers wrote:

Modern vaccinations, fear of germs and obsession with hygiene are depriving the immune system of the information input upon which it is dependent. This fails to maintain the correct cytokine balance and fine-tune T-cell regulation, and may lead to increased incidences of allergies and autoimmune diseases. If humans continue to deprive their immune systems of the input to which evolution has adapted it, it may be necessary to devise ways of replacing it artificially.

In a study published today in the Journal of the American Medical Association, University of Toronto researchers have uncovered widespread misinformation in related videos on YouTube.

The researchers, Dr. Kumanan Wilson and Dr. Jennifer Keelan, analyzed 153 videos about vaccination and immunization on YouTube, a popular online video-sharing site. Researchers found that more than half of the videos portrayed childhood, HPV, flu and other vaccinations negatively or ambiguously.

Of those videos, researchers report that about 45 per cent contained messages that contradict the 2006 Canadian Immunization Guide, which provides national guidelines for immunization practices. The Canadian recommendations are similar to guidelines from the American Centers for Disease Control and Prevention.

"YouTube is increasingly a resource people consult for health information, including vaccination," says first author Keelan, an assistant professor in U of T’s Department of Public Health Sciences. "Our study shows that a significant amount of immunization content on YouTube contradicts the best scientific evidence at large. From a public health perspective, this is very concerning."

The research team also found that videos skeptical of vaccinations—many of them highly provocative and powerful—received more views and better ratings by YouTube users than those videos that portray immunizations in a positive light.

"Health care professionals need to be aware that individuals critical of immunization are using YouTube to communicate their viewpoints and that patients may be obtaining information from these videos," says Wilson, senior author and an associate professor with U of T’s Department of Medicine. "YouTube users also need to be aware of this, so they can filter information from the site accordingly."

"The findings also indicate that public health officials should consider how to effectively communicate their viewpoints through Internet video portals," Wilson says.


Sources:

  • Journal of the American Medical Association, December 5, 2007
  • Universtiy of Toronto
  • Immunol Today, 1998 Mar;19(3):113-6.

Infertility and Testicular Cancer Linked, Says Study

University of California, San Francisco researchers have found that men with a history of infertility have a markedly increased risk of subsequently developing testicular cancer. The purpose of the study was to assess testicular cancer in infertile men usingna cohort study methodology.

More than 51,000 couples, drawn from 15 California infertility centers during the period 1965 and 1995, were evaluated for infertility. Male subjects’ medical records were linked to the California Cancer Registry, the cumulative Surveillance Epidemiology and End Results Registry (SEER) for the State of California. Cancers preceding infertility were excluded from analysis, and the incidence of testicular cancer in this cohort was compared to age-matched men from the general population.

The study found that men from infertile couples were 60% more likely to develop testicular cancer than other men (standardized incidence ratio 1.695% confidence interval 1.2 to 2.2). This risk was relatively constant across all age strata.

Source: UroToday

FDA: Spontaneous Hearing Loss due to Viagra, Levitra and Cialis

The United States Food and Drug Administration (FDA) approved labeling changes for Viagra, Cialis and Levitra that "more prominently display the potential risk of sudden hearing loss."

While rare, there have been reported incidents of single-sided hearing loss in patients taking the above erectile dysfunction drugs (Type 5 PDE5 inhibitors).

The labeling change was prompted by a published case of sudden hearing loss in a patient taking Viagra, and further studies found a total of 29 patients with sudden hearing loss.

There are no predictable warning signs for sudden hearing loss.

If you are taking these drugs and experience any hearing difficulty stop taking them at once and seek prompt medical attention.

From the FDA: "PDEF inhibitors are safe and effective for the treatment of ED when taken according to the labeling. However all drugs carry risks, and you should discuss any concerns you have regarding taking these products with your healthcare provider."