Association of human beta-herpesviruses with the development of cervical cancer: bystanders or cofactors

Background/Aim-Human papillomaviruses (HPVs) are important, but not suffici ent, for the development of cervical cancer. All three human beta -herpes-v iruses-cytomegalovirus (CMV) and human herpesviruses (HHV) types 6 and 7-ha ve been detected in the cervix. In addition, CMV and HHV-6 can interact wit h HPVs in vivo. This study examined the possible role of beta -herpesviruse s in cervical cancer development. Methods-HPV, CMV, HHV-6, and HHV-7 were detected by the polymerase chain re action using cervical scrapes taken at colposcopy from 388 women. HPV types were identified using restriction fragment length polymorphisms. Colposcop y guided biopsies were taken from abnormal areas, and the histological find ings were regarded as the final diagnoses. The associations between herpesv irus infection and the degree of cervical lesion were analysed with respect to HPV status. Results-Of the 388 women, 51.8% had a normal cervix, 14.4% had cervical int raepithelial neoplasia grade 1 (CIN1), 8.2% had CIN2, 19.3% had CIN3, and 6 .2% had invasive carcinoma. Overall, the positive rates for high, intermedi ate, and low risk HPVs were 18.8%, 21.4%, and 5.2%, respectively. Fifteen p atients harboured HPVs for which the genotype could not be identified. Posi tive rates for CMV, HHV-6, and HHV-7 were 9.5%, 3.6%, and 3.4%, respectivel y HPV positive patients carried a higher risk for high grade lesions (CIN2/ 3 or carcinoma) (odds ratio (OR), 5.24; 95% confidence interval (CI), 3.19 to 8.62; chi (2) = 51.79; p < 0.001), whereas those positive for CMV, HHV-6 , or HHV-7 did not. Thirteen of 131 patients with high grade lesions had HP V/herpesvirus coinfections, but no association with the cervical lesion was noted. Furthermore, positive rates for herpesviruses among HPV negative, h igh/intermediate risk HPV negative, and high risk HPV negative subgroups we re similarly low and without a significant association. Conclusions-The ubiquitous nature of herpesviruses may pose difficulty in e lucidating their pathogenic role, These results indicate that CMV, HHV-6, a nd HHV-7 are bystanders rather than cofactors in the oncogenesis of cervica l cancer.