Adeno-associated virus seropositivity and HPV-induced cervical cancer in Spain and Colombia

Abstract

Extensive experimental and limited epidemiologic data suggest that adeno-associated viruses (AAV) can have antioncogenic activity and may be protective factors for the development of cervical cancer. To examine the association between AAV-2 IgG antibodies and cervical neoplasia in Spain and Colombia, we tested for AAV-2 antibodies using an ELISA assay for 109 women with invasive cervical cancer, 100 population-based controls age-matched to the invasive cases, 77 women with carcinoma in situ (CIN III) and 100 clinic-based controls age-matched to the CIN III cases. Human papillomavirus (HPV) DNA was detected in cervical exfoliated cells by polymerase chain reaction using HPV-L1 and GP5+/6+ consensus primers. The prevalence of AAV-2 antibody titers >100 was significantly lower in invasive cervical cancer cases than control participants. When comparing women with invasive cancer with controls or with CIN III cases, a pattern of decreasing cervical cancer risk with increasing AAV-2 titers was observed. Elevated AAV antibody titers (>100) were inversely associated with invasive cervical cancer (OR 0.3; 95% CI 0.1-0.7), although results were not statistically significant after controlling for HPV (OR 0.4; 95% CI 0.1-1.6). In contrast, AAV-2 antibodies were not significantly associated with the risk of CIN III (OR 1.4; 95% CI 0.3-6.8). These results provide supportive evidence that AAV infection may be a protective factor for the development of invasive cervical cancer. Alternatively, the lower AAV-2 seroprevalence in invasive cervical cancer cases may be due to an immunosuppressive effect of cervical cancer on AAV antibody response. To investigate whether a direct viral interaction is occurring, future studies should aim to resolve at what frequency AAV is found in the genital tract and to clarify further whether AAV may infect the same HPV-positive cells in the cervix.