Cervical cancer and herpes simplex virus type 2: Case‐control studies in Spain and Colombia, with special reference to immunoglobulin‐G sub‐classes

Two case-control studies, including 449 histologically confirmed cases of cervical intra-epithelial neoplasia (CIN) III and 425 controls, and 2 studies on invasive cervical cancer, involving 316 histologically confirmed cases and 330 population controls, were conducted in Colombia and Spain to assess the role of herpes simplex virus type 2 (HSV-2) in cervical neoplasia. Antibodies to this virus were also measured in the sera of 931 husbands of cases and controls. A serological assay using type-specific antigens, glycoprotein C for type I (gC-I) and glycoprotein G for type 2 (gG-2) was employed. Immunoglobulin-G (IgG) sub-classes, IgG1 and IgG3, were measured in women positive for HSV-2 antibodies. No increase in risk of CIN III or invasive cancer was found in women whose sera or whose husbands' sera were positive to HSV-2. However, compared with women negative to HSV-2, the risk of CIN III progressively increased with increasing levels of IgG1. The trend was statistically significant in Colombia. There was also a statistically significant increasing trend in risk of invasive cancer with levels of IgG1 in Spain. The levels of IgG3 and its ratio to IgG1, which may indicate recurrent infections, were not associated with the risk of either type of cancer. When the association with IgG1 was analyzed by human papillomavirus (HPV) DNA status, as determined by polymerase chain reaction, the trend was clearer in women whose HPV status was not determined or in those with negative HPV DNA. These results suggest that the role of HSV-2 is merely marginal and do not support the hypothesis that recurrent HSV-2 infections are of importance for cervical neoplasia.