Herpesviruses as possible cofactors in HPV-16-related oncogenesis.
Cervical carcinogenesis is a complex problem with papillomavirus widely accepted as a causative agent. Integration of a human papillomavirus (HPV) of the high-risk type into the host cell genome is one of the major contributing factors to cervical malignant transformation. In this study, the correlation of CMV, EBV, HSV-1, HSV-2, HHV-6 and HHV-7 infections with the physical status of the HPV genome in cervical cancer and precancerous cervical lesions was investigated in sixty HPV-16-positive women. Cervical secretion samples were submitted to DNA extraction and analyzed by PCR. HPV-16 DNA was confirmed in genotyping with the reverse hybridization line probe assay. Multiplex PCR with specific primers for the E2/E6 genes was used to assess the viral integration status of HPV-16. Our results show that CMV DNA was more frequently present in samples with mixed forms of HPV-16 than in the episomal form (P < 0.025). Such a correlation was also observed in the case of EBV (P < 0.005). The presence of CMV resulted in a six-fold (OR 6.069; 95% CI 1.91-19.22; P = 0.002), while EBV caused a seven-fold (OR 7.11; 95% CI 1.70-29.67; P = 0.007) increase in the risk of the integrated or mixed HPV-16 genome occurrence. Our data suggest that coinfection with herpesviruses, especially CMV and EBV, may be involved in the integration of the HPV-16 genome and may contribute to the development of cervical cancer.
Szostek
Slawa
S
Department of Virology, Chair of Microbiology, Jagiellonian University Medical College, Kraków, Poland. sszostek@cm-uj.krakow.pl
Zawilinska
Barbara
B
Kopec
Jolanta
J
Kosz-Vnenchak
Magdalena
M
D000328:Adult; D000368:Aged; D002472:Cell Transformation, Viral; D002584:Cervix Uteri / Q000737:chemistry; D003587:Cytomegalovirus / Q000302:isolation & purification / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000150:complications / Q000453:epidemiology; D004279:DNA, Viral / Q000302:isolation & purification*; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000453:epidemiology; D005260:Female; D006564:Herpesviridae / Q000302:isolation & purification / Q000472:pathogenicity*; D006566:Herpesviridae Infections / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000472:pathogenicity; D052162:Human papillomavirus 16 / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D014626:Vaginal Smears; D016662:Virus Integration; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000821:virology
D004279:DNA, Viral