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. 2001 Jan;54(1):48–53. doi: 10.1136/jcp.54.1.48

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

P Chan 1, M Chan 1, W Li 1, D Chan 1, J Cheung 1, A Cheng 1
PMCID: PMC1731269  PMID: 11271789

Abstract

Background/Aim—Human papillomaviruses (HPVs) are important, but not sufficient, for the development of cervical cancer. All three human ß-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 ß-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; χ2 = 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.

Key Words: human papillomavirus • human herpesvirus 6 • human herpesvirus 7

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Figure 1 Restriction fragment length patterns of representative human papillomavirus (HPV) genotypes obtained by endonuclease digestion of L1 open reading frame (ORF) PCR products. Lane M: 25 bp ladder marker. Lanes 1–3: HPV6 not restricted, restricted with RsaI, and restricted with DdeI, respectively. Lane 4: blank. Lanes 5–7: HPV11 not restricted, restricted with RsaI, and restricted with DdeI, respectively. Lane 8: blank. Lanes 9–11: HPV33 not restricted, restricted with RsaI, and restricted with DdeI, respectively. Lanes 12–14: HPV58 not restricted, restricted with RsaI, and restricted with DdeI, respectively. Lane 15: blank. Lanes 16–18: HPV16 not restricted, restricted with RsaI, and restricted with DdeI, respectively. Lane 19: blank. Lanes 20–22: HPV18 not restricted, restricted with RsaI, and restricted with DdeI, respectively.

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Figure 2 Prevalence of human papillomavirus (HPV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), and HHV-7 in the cervix of 388 women with abnormal cervical cytologies by age groups. Numbers of patients tested in each age group: ≤ 30 years, 56 patients; 31–40 years, 159 patients; 41–50 years, 115 patients; > 51 years, 58 patients. Squares, HPV; circles, CMV; triangles, HHV-6; crosses, HHV-7.

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