Almost all cases of invasive cancers of the cervix and most other anogenital tract cancers are associated with high-risk HPV types (predominantly types 16, 18, 31 and 45). Although tobacco and alcohol use are the primary risk factors associated with head and neck squamous cell carcinoma (HNSCC), HPV is also associated with ~25% of these tumors. The prevalence of HPV-positive HNSCC is highest in the oropharynx, especially the tonsils. The source of HPV infection to the oral mucosa is still unclear and the role of HPV infection in the development of HNSCC after a first diagnosis of cervical cancer is unknown. Using SEER data, we compared the risk of second primary (SPC) HNSCC in cervical cancer patients to the general population and to females with other primary cancers. The lifetime risk of developing SPC in the pharynx of cervical cancer patients was significantly higher than in the general population (SIR: oropharynx = 2.7; the tonsil only = 3.1 and hypopharynx = 2.8). When compared to females with other cancers, the risk of SPC in the pharynx, vagina, vulva and anus/anal canal was in excess in cervical cancer patients, while the risk of SPC in the other head and neck subsites (oral cavity, nasopharynx and salivary glands) were not in excess. The relative risk of SPC among females with cervical cancer was compared to that of age-matched female breast and urinary bladder cancer patients, to indirectly assess whether the risk of second primary tumors in head and neck sub-sites among cervical cancer patients was to be mostly attributed to persistence of smoking. The risk of second primary lung cancer was significantly higher in women who had cervical or bladder cancer, while it was not increased in women with breast cancer. As expected, cervical cancer patients were at risk of developing HPV-related second primary tumors arising in the vagina (SIR = 23.7), vulva (SIR = 4.0) and anus/anal canal (SIR = 3.4). Breast and bladder cancer patients were not at risk for these second primary tumors. For the development of SPC in the oropharynx, female breast and bladder cancer patients were not at increased risk (SIR oropharynx = 1.0 and 1.1, respectively). However, for cervical cancer patients, the risk of SPC in the oropharynx was elevated 3-fold (SIR = 2.8 for the oropharynx, 3.5 for the tonsils only). Our findings show that cervical cancer patients develop an excess HNSCC SPC in comparison to females with other cancers. A possible role of HPV is suggested.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA