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Star Calls Attention to Oral Sex Throat Cancer Link, Raising Awareness of HPV Vaccine

Actor Michael Douglas' claim that his throat cancer was caused by oral sex has brought new attention to the link between human papillomavirus (HPV) and oral cancer, as well as heightened interest in HPV vaccination for both girls and boys. Recent studies suggest that spouses of people with oral cancer are not themselves at higher risk, 2 vaccine doses may work as well as 1, and vaccination has already reduced genital warts in Australia.

There are more than 100 known types of HPV. Most people become infected soon after they become sexually active. Many individuals naturally clear the virus, but in others it persists and can cause abnormal cell changes. Types 16 and 18 are the main causes of cervical, anal, vulva, penis, and probably oral cancers, although several other types are also oncogenic. HPV types 6 and 11, among others, cause genital warts.

The link between HPV and oropharyngeal (mouth and throat) cancers first started showing up in the 1990s, and some experts have attributed the rise in oral cancers to increased cultural acceptance of oral sex. As described in the June 15, 2013, issue of Cancer, George Kurdgelashvili and colleagues found that the incidence of early-stage cervical, penis, anal, and head/neck cancers all increased in the U.S. between 1978 and the advent of widespread HPV vaccination in 2007.

According to the U.S. Centers for Disease Control and Prevention (CDC), 8400 cases of oropharyngeal cancer annually are attributable to HPV, 80% of them among men. This compares with 12,000 cases of cervical cancer, 4300 cases of anal cancer (two-thirds among women), 2600 cases of vulva and vaginal cancer, and 600 cases of penis cancer.

Douglas' announcement in an interview in the June 2, 2013, edition of the UK Guardian was greeted with some skepticism, since it is difficult to determine the exact cause of cancer in a specific individual, and his heavy smoking and drinking are also known risk factors for oral cancers.

There is no treatment for HPV, but early detection and management of precancerous cell changes (dysplasia or neoplasia) can prevent progression to invasive cancer. Regular cervical screening with Pap smears and HPV testing has dramatically reduced the incidence of cervical cancer. Some experts recommend that men who have sex with men -- especially if HIV positive -- should undergo regular anal Pap screening, but this is not yet a widely established standard of care. Oral screening is not yet available, but visual examination during dental exams can help catch tumors early.

Risk for Spouses

Perfectly timed to take advantage of the recent flurry of media interest, a poster presented at the American Society of Clinical Oncology Annual Meeting (ASCO 2013) taking place this week in Chicago suggests that regular sexual partners of people with oral cancer do not appear to be at greater risk themselves.

Gypsyamber D'Souzafrom Johns Hopkins Bloomberg School of Public Health and fellow investigators with the Human Oral Papillomavirus Transmission in Partners Over Time (HOTSPOT) study looked at 166 patients with HPV-related oropharyngeal cancer and 94 spouses or long-term partners. Most of the cancer patients (89%) were men, almost all reported oral sex, and half said they had never smoked. Most of the spouses (about 80%) were women, and again half had never smoked.

Oral HPV infection was common among the oral cancer patients at 65%, including 54% with high-risk HPV-16; 1 year after cancer treatment the rate dropped to 6%. The overall infection rate among partners was much lower, at just 7% -- similar to that of the general population. But the rate was significantly higher for male partners in the study (33%) than for female partners (5%). Two female partners were found to have HPV-16, but this was no longer detected after 1 year of follow-up. Among the two-thirds of spouses who had visual oral exams, no oral pre-cancer or cancer was detected; 2 spouses, however, had a history of cervical cancer.

"Oral HPV16 DNA is common among [HPV oral cancer patients], but not among their spouses," the researchers concluded.

HPV Vaccination

Since most people become infected with HPV soon after they start having sex, vaccination is recommended for pre-teens before this occurs. The CDC now recommends HPV vaccination for both girls and boys age 11-12 years, and for young adults up to age 26 (for women) or 21 (for men) who were not previously vaccinated. Gardasil, Merck's quadrivalent vaccine, is effective against HPV 6, 11, 16, and 18. GlaxoSmithKline's Cervarix is effective only against types 16 and 18. The CDC estimates that 21,000 of the nearly 28,000 annual cases of HPV-related cancer could potentially be prevented by timely vaccination.

The current recommended HPV vaccine course consists of 3 doses administered over 6 months, but a 2-dose vaccine could increase the likelihood of complete immunization. As described in the May 1, 2013, Journal of the American Medical Association, Simon Dobsonform the University of British Columbia found that 2 doses of the quadrivalent vaccine administered 6 months apart to girls age 9-13 years worked as well as the usual 3 doses for young women age 16-26 years.

It is not clear yet whether immune response to all covered HPV types will be durable over the long-term, however. In an accompanying editorial, Jessica Kahn and David Bernstein from Cincinnati Children's Hospital Medical Center suggested it is too soon to recommend the 2-dose schedule, but more study is warranted.

"If future studies establish that a 2-dose series leads to a durable immune response and effectively prevents HPV-related cancers in both women and men, the benefits would be substantial for reducing the global burden of cervical cancer and other HPV-related diseases," they wrote. "The potential to further reduce morbidity and mortality due to HPV-related cancers would be especially significant in less developed regions of the world, where the cost of vaccination and implementation of adolescent vaccination programs present significant barriers, but where primary prevention strategies are most urgently needed."

While HPV vaccination is primarily promoted for preventing cancer, Gardasil was recently shown to significantly reduce the incidence of genital warts among young people in Australia.

As reported in the April 18, 2013, British Medical Journal, Hammad Ali from the Sydney Sexual Health Centre looked at changes in occurrence of genital warts since the national HPV vaccination program started in mid-2007.

They found that the prevalence of genital warts among women under age 21 declined from 11.5% in 2007 to 8.5% in 2011, while the rate for 21-30 year-old women fell from 11.3% to 3.1%. No significant decline was seen for women over 30. Among heterosexual men, the wart rate fell 12.1% to 2.2% for men under 21 and from 18.2% to 8.9% in the 21-30 age group, again with no significant decrease for older men.

In 2011 no genital wart diagnoses were made among 235 women under age 21 who received HPV vaccines. Since vaccination was not instituted until later for young men, the researchers suggested their decline was "probably due to herd immunity."

6/6/13

References

G D'Souza, ND Gross, SI Pai, et al. Oral HPV infection in HPV-positive oropharyngeal cancer cases and their spouses. American Society of Clinical Oncology Annual Meeting (ASCO 2013). Chicago, May 31-June 4, 2013. Abstract CRA6031/111185-132. Also Journal of Clinical Oncology 31, 2013 (suppl; abstr CRA6031).

SR Dobson, S McNeil, M Dionne, et al. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. Journal of the American Medical Association 309(17):1793-1802. May 1, 2013.

JA Kahn and DI Bernstein. HPV vaccination: too soon for 2 doses? (Editorial).Journal of the American Medical Association 309(17):1832-1834. May 1, 2013.

H Ali, B Donovan, H Wand, et al. Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillancedata. British Medical Journal 346:f2032. April 18, 2013.

G Kurdgelashvili, GM Dores, SA Srour, et al. Incidence of potentially human papillomavirus-related neoplasms in the United States, 1978 to 2007. Cancer 119(12):2291-2299. June 15, 2013.

Other Sources

C Shoard.  Michael Douglas: oral sex caused my cancer. Guardian UK. June 2, 2013.

JAMA. Study Finds That 2 Doses of HPV Vaccine in Girls May Offer Similar Level of Infection Protection as 3 Doses in Young Women. Media advisory for April 30, 2013.

U.S. Centers for Disease Control and Prevention (CDC). Genital HPV Infection -- Fact Sheet. Last updated March 18, 2013.

U.S. Centers for Disease Control and Prevention (CDC). HPV Vaccine -- Questions and Answers. Last updated July 20, 2012.