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MEDICINE

HPV and male cancer

Infection may lead to genital warts within six months or precancerous lesions within two years

Kateryna Kon / Science Photo Library In January 2017, Brazil’s public healthcare system began vaccinating boys aged 12 to 13 against the human papillomavirus, or HPV. By early June, however, only 595,000 male adolescents (16.5% of this age bracket) had received the first of the two doses of an imported vaccine that protects against infection by four types of the virus. Transmitted through contact with the skin or mucous during sex, HPV has been linked to the development of genital and anal warts in men, as well as to tumors of the penis, anus, mouth, and throat. Since condom use does not always prevent transmission of the virus, health experts say that the best way to fight the spread of the disease is by vaccinating the uninfected population. In late June, the Brazilian Ministry of Health recommended expanding the vaccine bracket for boys to encompass ages 11 to 14, thus making it more challenging to meet the goal of 80% coverage by the end of 2017. Although the vaccine has been available longer for girls, this rate has yet to be achieved even among them.

Shortly after the publication of studies that have begun revealing how the virus progresses and how long it takes to produce genital warts and precancerous lesions in males, it became evident that efforts to protect boys would have to be stepped up. “It’s long been known that HPV also triggers the development of warts and tumors in the male genital region, but there was no research measuring the probability that an infection would produce a lesion or how long it would take for this to happen,” says biochemist Luisa Lina Villa, professor at the University of São Paulo School of Medicine (FMUSP). In the 1980s, Villa was one of the first Brazilian researchers to identify the presence of HPV in penile tumors, and for nearly 10 years she has led the Brazilian part of the epidemiological study “HPV Infection in Men (HIM).” Funded by FAPESP, the National Cancer Institute in the United States, and the pharmaceutical company Merck Sharp & Dohme—maker of the 4-valent Gardasil vaccine—the study followed the sexual health of 4,100 men aged 18 to 73 in Brazil, Mexico, and the United States for nearly five years.

The HIM study has already yielded dozens of scientific articles. Three of these, published between 2015 and 2017, offer more in-depth analyses of the natural progression of HPV infection. In two of these papers, the team led by Anna Giuliano—epidemiologist with the Moffitt Cancer Center, in Florida, and HIM leader—has reported findings from evaluations of around 3,000 of the men.

At the beginning of the study, none of those enrolled had either a sexually transmitted disease or HPV infection. Over time, a portion of the men contracted the virus, as identified through genetic testing of material collected from the penis and scrotum. Approximately 72% of the Brazilians were infected with HPV at some point during the research, a significantly higher rate than observed among participants from Mexico (62%) or the United States (61%). Of the 37 HPV types investigated, four were detected more often; two of these are considered to present a low risk of causing tumors (HPV6 and HPV11), while two are deemed high risk (HPV16 and HPV18). The vaccine that is offered free through Brazil’s healthcare system provides immunity against these four types.

One of the evaluations was based on data from 3,033 men from the three countries. Of this total, 1,788 were infected by at least one type of HPV, and 86 of them (5% of those infected) developed genital warts (condyloma). Only nine of those with HPV presented the precancerous lesions known as penile intraepithelial neoplasias.

One in every four cases of HPV6 or HPV11 infection produced condyloma containing the same virus. The time between infection and appearance of the warts was nearly eight months for the first virus and four for the second. Close to 60% of the precancerous lesions contained high-risk HPV16. In most cases, it was nearly two years from infection to development of the neoplasia, according to an article published in the journal European Urology in 2015.

The analysis of Brazilian data was published in the Brazilian Journal of Infectious Diseases in April 2017. Of the 1,118 men enrolled from São Paulo, 815 had HPV and 35 developed genital lesions. During follow-up, 16% of those with HPV6 and 16% of those with HPV11 developed genital warts within nine months and seven months, respectively, a slower pace than that identified among the men from Mexico and the United States. In the Brazilian sample, 1% of those with HPV16 developed a precancerous lesion within 25 months.

In its conclusion, the Brazilian study calls attention to the fact that HPV types 6, 11, 16, and 18—against which the 4-valent vaccine affords protection—were found in 80% of the condyloma and precancerous lesions. The study also states that it would recommend adopting a broader vaccination policy for boys, since males continue to contract the infection throughout their lives and transmit it to their partners, both male and female. In one of the HIM articles, researchers point to the successful case of Australia, the first country to enforce a national HPV immunization program. Vaccine coverage surpasses 80% there, and the rate of genital warts among women has dropped 70% to 90%.

Fernando Pereira / SECOM - PMSP Adolescent receives HPV vaccine at a public healthcare clinic in the city of São PauloFernando Pereira / SECOM - PMSP

Lower coverage
Such success seems like a distant goal in Brazil. The HPV vaccine is expensive; one dose costs the Ministry of Health around R$40, while private clinics charge R$400 for it. Since 2014, when the vaccine was made available to girls, 72.5% of those aged 9 to 15 have received the first dose and 43%, the second. This rate fell after immunization was no longer offered in schools. The circulation of news stories concerning side effects associated with the vaccine—which, although rare, do exist—may partly account for the drop-off. The most common side effects include pain, itching, and local swelling, along with nausea, headache, and limb pain. While there have also been sporadic reports of fainting, seizures, and transient loss of sensitivity in the limbs, subsequent investigations classified these cases as post-vaccine psychogenic reactions, a psychological phenomenon that has been documented in other vaccine campaigns.

“We are working to increase coverage,” says Carla Domingues, coordinator of the Ministry of Health’s National Immunization Program. “The ministry recommends that municipalities offer the vaccine at schools, but this demands complex logistics.” To reach the goal of 80%, advertising campaigns are set to begin in July 2017 to encourage parents to take their adolescent children to public healthcare posts and complete their immunization schedule, including the HPV vaccine.

Villa advocates bringing vaccines back to schools. In her opinion, reducing the risk of HPV infection depends on educating young people to practice safe sex and vaccinating people who have not been exposed to the virus. “To change this story, all of these kids have to be vaccinated,” she says. “People haven’t gotten the message yet.”

Project
Institute of Science and Technology for the study diseases associated with papillomavirus (No. 08/57889-1); Grant Mechanism Thematic project; Program National Institutes of Science and Technology (INCTs); Principal Investigator Luisa Lina Villa (FMUSP); Investment R$4,990,411.77.

Scientific articles
SILVA, R. J. C. et al. HPV-related external genital lesions among men residing in Brazil. Brazilian Journal of Infectious Diseases. April 8, 2017.
SUDENGA, S. L. et al. Genital Human Papillomavirus infection progression to external genital lesions: The HIM Study. European Urology. V. 69, No. 1, pp. 166-173. June 6, 2015.

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