Frequency and clinical significance of human beta-herpesviruses in cervical samples from Italian women

Human papillomaviruses (HPVs) are necessary, but not sufficient, for the development of cervical cancer (CC). Human beta-herpesviruses (beta-HHVs) have been suggested as possible cofactors in the oncogenesis of CC. In this cross-sectional study, the prevalence and possible association of cytomegalovirus (CMV), HHV-6 and -7 with HPV presence was investigated by quantitative real-time PCR assays in cervical samples obtained from 208 italian women. The two most common high-risk HPV types found were 31 and 16. Overall, the positive rates for CMV, HHV-6 and HHV-7 were 66%, 25%, and 6%, respectively. In particular, the prevalence of CMV was found to be extremely high irrespective of either the cytological category or HPV positivity. The prevalence of HHV-6 DNA was significantly higher in high-grade squamous intraepithelial lesions (HSIL) respect to normal women (P < 0.017); by contrast, the prevalence HHV-7 DNA was generally low and not associated with SIL. Copresence of CMV and HHV-6 DNA was found to be significantly higher in patients with SIL respect to normal women (P < 0.05). No correlation was demonstrated between the viral load of all three beta-HHVs and the different cytological stages or with the HPV presence. A few patients with severe disease however showed very high viral loads which for HHV-6 may be indicative of viral integration. In conclusion, this study suggests that CMV and HHV-7 alone are probably not implicated in the oncogenesis of CC whilst HHV-6 alone or together with CMV may contribute to the development of CC