Familial clustering of cancer at human papillomavirus-associated sites according to the Swedish Family-Cancer Database

Familial aggregation of cervical cancer has been demonstrated previously, however aggregation of other human papillomavirus-associated anogenital, upper aerodigestive tract and skin cancers has not been fully characterized. The Swedish Family-Cancer Database, which contains reliable data on cancer incidence and nuclear family linkages for all residents of Sweden between 1958 and 2004, was used to calculate standardized incidence ratios (SIR) and 95% confidence intervals for offspring site-specific cancer risks according to site-specific cancer in sibling and parental probands. Offspring cancer risk was significantly increased when either a sibling or parent was affected at the same site for penile squamous cell carcinoma (SCC, SIR = 7.54), cervical adenocarcinoma (AC, SIR = 2.31), vulvar SCC (SIR = 2.27), skin SCC (SIR = 2.14), rectal AC (SIR = 1.86), in situ cervical SCC (SIR = 1.80), invasive cervical SCC (SIR = 1.77) and upper aerodigestive tract SCC (SIR = 1.57). Significant aggregation on the order of 2-fold between anogenital cancers at different sites or histologies was also observed. In situ cervical SCC risk in offspring was strongly influenced by siblings affected with oropharyngeal SCC (SIR = 3.17) and tonsillar SCC (SIR = 1.84). Familial skin SCC was largely unassociated with anogenital or upper aerodigestive tract cancer risk in offspring. These data suggest that common host factors exist among individuals affected with anogenital and upper aerodigestive tract cancers.