Association of human beta-herpesviruses with the development of cervical cancer: bystanders or cofactors.
OBJECTIVE
Human papillomaviruses (HPVs) are important, but not sufficient, for the development of cervical cancer. All three human beta-herpesviruses--cytomegalovirus (CMV) and human herpesviruses (HHV) types 6 and 7--have been detected in the cervix. In addition, CMV and HHV-6 can interact with HPVs in vivo. This study examined the possible role of beta-herpesviruses in cervical cancer development.


METHODS
HPV, CMV, HHV-6, and HHV-7 were detected by the polymerase chain reaction using cervical scrapes taken at colposcopy from 388 women. HPV types were identified using restriction fragment length polymorphisms. Colposcopy guided biopsies were taken from abnormal areas, and the histological findings were regarded as the final diagnoses. The associations between herpesvirus 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 intraepithelial neoplasia grade 1 (CIN1), 8.2% had CIN2, 19.3% had CIN3, and 6.2% had invasive carcinoma. Overall, the positive rates for high, intermediate, and low risk HPVs were 18.8%, 21.4%, and 5.2%, respectively. Fifteen patients harboured HPVs for which the genotype could not be identified. Positive rates for CMV, HHV-6, and HHV-7 were 9.5%, 3.6%, and 3.4%, respectively. 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 HPV/herpesvirus coinfections, but no association with the cervical lesion was noted. Furthermore, positive rates for herpesviruses among HPV negative, high/intermediate risk HPV negative, and high risk HPV negative subgroups were similarly low and without a significant association.


CONCLUSIONS
The ubiquitous nature of herpesviruses may pose difficulty in elucidating their pathogenic role. These results indicate that CMV, HHV-6, and HHV-7 are bystanders rather than cofactors in the oncogenesis of cervical cancer.
Chan
P K
PK
Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China. paulkschan@cuhk.edu.hk
Chan
M Y
MY
Li
W W
WW
Chan
D P
DP
Cheung
J L
JL
Cheng
A F
AF
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D003587:Cytomegalovirus / Q000302:isolation & purification / Q000472:pathogenicity; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006564:Herpesviridae / Q000302:isolation & purification* / Q000472:pathogenicity; D015654:Herpesvirus 6, Human / Q000302:isolation & purification / Q000472:pathogenicity; D016199:Herpesvirus 7, Human / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification; D016133:Polymerase Chain Reaction / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000821:virology
D004279:DNA, Viral