Low-risk human papillomavirus type 6 DNA load and integration in cervical samples from women with squamous intraepithelial lesions

Abstract

Background: The association between human papillomavirus (HPV) viral load and high-grade squamous intraepithelial lesion (HSIL) of the uterine cervix has been demonstrated for high-risk HPV-16 but has not been investigated for low-risk HPV types.

Objective: To determine the association between the presence of low-grade SIL (LSIL) and viral load of low-risk HPV type 6.

Study design: 107 HPV-6-positive cytobrush samples collected from 90 women (67 without SIL, 11 with LSIL, 5 with HSIL, 6 with SIL of unknown grade and 1 with a smear with LSIL and a normal colposcopy) were analyzed for their content of HPV-6 DNA.

Methods: HPV-6 E6 and E2 DNA loads were measured in the cytobrush samples with two real-time PCR assays. HPV-6 integration was confirmed with restriction-site PCR.

Results: HPV-6 DNA in cervical samples ranged from 1.8 x 10(2) to 4.25 x 10(8) copies per microg of cellular DNA. HPV-6 E6 DNA loads were higher in women with LSIL, with or without co-infection with high-risk HPV types, than in women without SIL (p=0.03). HPV-6 loads greater than 8.76 x 10(6)copies per microgDNA, corresponding to the mean HPV-6 load measured in women with LSIL, were more frequently detected in these women with LSIL than in women without LSIL, controlling for age (odds ratio 13.5, 95% confidence interval 1.1-172.4). Although 10 samples generated HPV-6 E6/E2 ratios above 2, there was no evidence of integration of HPV-6 by restriction-site PCR.

Conclusion: Samples from women with LSIL contained higher HPV-6 loads than women without SIL. HPV-6 DNA was not integrated into cellular DNA in these samples.