The present study has provided prospective epidemiological evidence that infection with HPV 16 and 18 does confer an increased risk for future anal and perianal skin cancer. The highest risks were seen for HPV 16 seropositive patients above the age of 45 years at serum sampling and for patients with a lag time of less than 10 years.
The role of a sexually transmitted agent in the etiology of anal cancer was first suggested in 1979 (Cooper et al, 1979
). Similar to the cervix, the anal canal has a squamocolumnar junction or transformation zone, which appears to be particularly susceptible to HPV infection, and the concomitant risk of intraepithelial neoplasia and carcinoma (Tilston, 1997
). It is now well established that HPV play a central role in the pathogenesis of anogenital cancers and their precursors (International Agency for Research on Cancer, 1995
; Ryan et al, 2000
). HPV DNA has been detected in invasive as well as in anal squamous intraepithelial lesions. HPV 16 is the most common type found. In situ
hybridisation studies have found 24–73% of cases to be HPV DNA positive, whereas the corresponding figures for Southern blot and PCR studies are 63–85% and 24–100%, respectively (International Agency for Research on Cancer, 1995
). HPV DNA is almost always found integrated into the host chromosome, but it is frequently coexistent with episomal DNA in the cell nucleus (Holm et al, 1994
; Tilston, 1997
However, the detection of HPV DNA implies current infection only. Prior exposure is not necessarily reflected. By applying HPV serology, a marker of both past and present HPV infection, it has been possible to investigate possible temporal associations of HPV infection with anal cancer. Previously, a serologic association of HPV 16 with incident anal cancer has been reported (Heino et al, 1995
). In our previous, prospective study, no association of HPV and anal cancer was found, although a high, but insignificant risk was found for perianal skin cancer (Bjørge et al, 1997a
). The present expanded study is, to our knowledge, the first study providing prospective epidemiologic evidence of an association between HPV infection and anal and perianal skin cancer. Subjects seropositive for HPV 16 and also for HPV 18 were at an increased risk.
Patients with HPV DNA in their anal tumours have been reported to be about 10 years younger than those with HPV DNA-negative anal cancers (Heino et al, 1993
). In this study, the mean age of the cases being seropositive for any HPV was 54 years, whereas the mean age of the seronegative cases was 53 years.
At present, the incidence of anal cancer is about two to three times higher in women than in men. Particularly in women, the incidence has increased substantially over the past decades. A higher proportion of anal cancer cases has been reported to be positive for HPV DNA in women compared to men (Holm et al, 1994
; Frisch et al, 1997
). In the present study, 28% of the female and 30% of the male cases were seropositive for HPV 16. Similar figures for HPV 18 were 17% and 20%, respectively.
In summary, this study provides prospective epidemiological evidence indicating that infection with HPV 16 and also HPV 18 does increase the risk for subsequent development of anal and perianal skin cancer.