Extensive experimental and limited epidemiologic data suggest that adeno-as
sociated viruses (AAV) can have antioncogenic activity and may be protectiv
e factors for the development of cervical cancer. To examine the associatio
n 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 in
vasive cervical cancer, 100 population-based controls age-matched to the in
vasive cases, 77 women with carcinoma in situ (CIN III) and 100 clinic-base
d controls age-matched to the CIN III cases. Human papillomavirus (HPV) DNA
was detected in cervical exfoliated cells by polymerase chain reaction usi
ng HPV-LI and GP5+/6+ consensus primers. The prevalence of AAV-2 antibody t
iters > 100 was significantly lower in invasive cervical cancer cases than
control participants. When comparing women with invasive cancer with contro
ls 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 controlli
ng for HPV (OR 0.4; 95% Cl 0.1-1.6). In contrast, AAV-2 antibodies were not
significantly associated with the risk of CIN III (OR 1.4; 95% Cl 0.3-6.8)
. These results provide supportive evidence that AAV infection may be a pro
tective factor for the development of invasive cervical cancer. Alternative
ly, the lower AAV-2 seroprevalence in invasive cervical cancer cases may be
due to an immunosuppressive effect of cervical cancer on AAV antibody resp
onse. To investigate whether a direct viral interaction is occurring, futur
e studies should aim to resolve at what frequency AAV is found in the genit
al tract and to clarify further whether AAV may infect the same HPV-positiv
e cells in the cervix. (C) 2001 Wiley-Liss, Inc.