HPV Causing "Slow Epidemic" of Oral Cancers
October 21, 2010 — Human papillomavirus (HPV) is a risk factor for oropharyngeal squamous cell carcinoma (OSCC), and might account for the steady increase in OSCC incidence, even in subjects who do not smoke or consume alcohol, according to Swedish researchers.
A review of recent studies, conducted by Trobjorn Ramqvist, MD, and Tina Dalianis, MD, PhD, and published online October 13 in Emerging Infectious Diseases, suggests that changes in sexual practices are behind the surge in OSCC cases linked to sexually transmitted HPV. The key factors appear to be multiple sex partners, starting sexual activity at a younger age, and increased oral sex.
The data are startling. For example, from 1970 to 2002, tonsillar cancer (which is the most common OSCC) increased in Stockholm, Sweden, by 2.8-fold, and by 2006/07, 93% of all tonsillar cancers in that city were HPV-positive.
Dr. Dalianis, who is professor of tumor virology and the head of the Department of Oncology–Pathology at Karolinska Institutet in Stockholm, told Medscape Medical News that "we realized that there was an increase in HPV-induced tonsillar cancer, but we did not realize it was so eminent until we separated the 2 groups (HPV-negative and -positive tonsillar cancer cases) the way we did."
The most common OSCC is tonsillar cancer, followed by base of tongue cancer. Overall 5-year survival for OSCC is about 25%, and HPV-positive OSCC generally has better clinical outcomes than HPV-negative disease.
Dr. Dalianis said that HPV (most commonly type 16) was found in 45% to 100% of OSCCs in various studies.
"It was also observed that patients with HPV-positive OSCC were younger and lacked the traditional risk factors of smoking and alcohol consumption," the authors write. "We suggest the increased incidence of OSCC depends on HPV infection and results in an increased proportion of HPV-positive OSCCs."
Dutch Expert Questions Proportions of HPV Positivity
Using data from the Swedish Cancer Registry, the researchers found that the incidence of HPV-positive tonsillar tumors almost doubled over each decade from 1970 to 2007, for a cumulative 7-fold increase over that period.
Similarly, HPV-positive base of tongue cancers increased from 54% in 1998/99 to 84% in 2006/07.
However, another expert, asked to comment on the study by Medscape Medical News, raised questions about the high proportion of HPV-positive tumors found in the Stockholm registry data.
Boudewijn J.M. Braakhuis, PhD, is from the section of tumor biology in the Department of Otolaryngology/Head and Neck Surgery at VU University Medical Center in Amsterdam, the Netherlands. Dr. Braakhuis, whose work focuses on oral and oropharyngeal cancers, said that the proportion of HPV-positive OSCCs in the Amsterdam area is about 20%.
Dr. Braakhuis said that the Swedish analysis is hampered by the lack of a standardized method for measuring HPV involvement. Dr. Braakhuis's group proposes doing p16 staining followed by general primer polymerase chain reaction with typing, which might reduce the risk for false positives.
The Case for HPV Vaccination
Dr. Dalianis said that there is a significant association of HPV-positive tonsillar cancer with early initial sex, and with the number of oral or vaginal sex partners. She also noted that one study reported "that not only oral sex, but also open-mouthed kissing, was associated with the development of oral HPV infection."
Noting that this could mean that oral-to-oral contact might play a role in oral HPV transmission, Dr. Dalianis said that this has implications for the timing of vaccinating children to prevent HPV.
Dr. Dalianis is "a strong supporter of giving the HPV vaccine to both girls and boys," and writes that "it is crucial to monitor the effects of the present HPV vaccination, not only on the incidence of cervical cancer but also on the incidence of OSCC."
Dr. Braakhuis agreed: "One may expect that vaccination will decrease the number of HPV-positive oropharyngeal cancers" after decades.
Another important point uncovered in the review is that the incidence of head and neck squamous cell carcinoma is decreasing and OSCC is increasing, which might presage a risk for overtreatment if the intensified regimens used for head and neck squamous cell carcinoma are applied to HPV-positive OSCC, which has a better prognosis than HPV-negative disease.
"It is possible that increasing numbers of OSCC patients with a better prognosis are being treated with intensified therapy. As a result, many patients have substantial chronic unnecessary side effects. It is therefore necessary to identify which patients need and which do not need intensified treatment," the study authors write. The suggestion is that OSCC patients with HPV-positive tumors who have never smoked might be candidates for less intensive treatment.
Dr. Dalianis and Dr. Braakhuis have disclosed no relevant financial relationships.
Emerg Infect Dis. 2010;16:1671-1677.