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HPV Vaccine's Benefits Are Mainly Extracervical


 

EXPERT ANALYSIS FROM A CONFERENCE ON PEDIATRIC INFECTIOUS DISEASES SPONSORED BY CHILDREN'S HOSPITAL COLORADO

VAIL, COLO. – The human papillomavirus vaccine is still widely perceived as a tool aimed at preventing cervical cancer, yet in fact roughly 55% of all the cancers it should protect against occur at other sites, according to Dr. Myron J. Levin.

The extracervical malignancies associated with HPV types covered by the two commercially available vaccines include anorectal and oropharyngeal cancers in both women and men, as well as penile cancer.

Indeed, one-third of all HPV-related cancers occur in men, not in women, which is one reason that last year the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommended routine HPV vaccination for 11- to 12-year-old boys, as is already the case for girls of the same age. Also, protecting boys will secondarily increase protection against cervical cancer in girls.

In light of the vaccine’s impressive clinical benefits, favorable cost-benefit estimates, and excellent safety record to date, the lagging U.S. HPV vaccination rates are disturbing, Dr. Levin said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado. Data from the CDC’s 2010 National Immunization Survey – Teen indicate only 23% of 13-year-old girls had received the three-dose series. The Healthy People 2020 goal is for 80% of 13- to 15-year-olds to have received three doses.

Even though the recommendation is for routine immunization at age 11-12, it’s Dr. Levin’s impression that many physicians are putting it off until their patients are 15-17 years old.

"I think we’re making a mistake. I think we’re missing a big opportunity. A significant number of girls become sexually active before age 15, and waiting until they’re that age to immunize them may compromise their chance of protection. All those favorable cost-benefit analyses don’t count if you don’t get the vaccine," said Dr. Levin, professor of pediatrics and medicine at the University of Colorado at Denver.

HPV is the most common sexually transmitted infection worldwide. Three-quarters of the general population become infected, and three-quarters of those infections occur at 15-24 years of age. Moreover, more than 50% of those who become infected do so within 2 years after becoming sexually active – and studies show that more than 20% of males and females have already had vaginal sex by age 15.

Beyond the whole issue of vaccine-preventable HPV-associated cancers, there is the matter of genital warts, or condylomata acuminata. The incidence of genital warts is about 1% per year among sexually active people. In 2010 there were 376,000 initial physician office visits for genital warts, according to data from the National Disease and Therapeutic Index. The cost of treatment is $300-$1,000 per case, and recurrences are common. Up to 90% of cases of genital warts are caused by HPV types 6 and 11, two of the four types targeted by one of the two commercially available vaccines. The incubation period for genital warts is just a few months, compared with years or decades for HPV-related malignancies.

Dr. Levin highlighted landmark research from Australia demonstrating the profound impact widespread adoption of the quadrivalent HPV vaccine can have at the population level. Australia was the first country to fund a vaccination program for all females aged 12-26 years, starting in July 2007. A national surveillance program demonstrated a 59% reduction in new diagnoses of genital warts among women eligible for the free vaccine during the first 2 years after the program started (Lancet Infect. Dis. 2011;11:39-44).

Interestingly, there was also a 39% drop in new cases among heterosexual Australian males aged 12-26, even though they weren’t included in the vaccine program. This is evidence of herd immunity, Dr. Levin said. In contrast, rates remained unchanged among men who have sex with men.

In a subsequent report with updated data through mid-2011, Australian investigators described "the dramatic decline and near disappearance" of genital warts in women and heterosexual men under age 21 years 4 years after the start of the national HPV vaccination program targeting females (Sex. Transm. Infect. 2011;87:544-7).

One development worth keeping an eye on is the possibility that patients may not really need three doses of HPV vaccine to be protected, Dr. Levin said. This prospect was raised by investigators at the National Cancer Institute, who observed in a large Costa Rican randomized clinical trial that the efficacy of GlaxoSmithKline’s bivalent HPV 16/18 vaccine was comparable after a median 4.2 years of follow-up in women who didn’t come back for their third dose and in those who received all three. Since the three-dose regimen is expensive and difficult to complete, a two-dose strategy could be particularly important in resource-poor countries (J. Natl. Cancer Inst. 2011;103:1444-51).

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