Abstract

HPV16 variants correlate with geographic origin and ethnicity. The association between infection with a specific variant and the cervical disease risk remains unclear. We studied the prevalence, persistence and association with cervical intraepithelial neoplasia (CIN) of different HPV16 variants, using cervical swabs and whole tissue sections (WTS) of biopsies from 548 women in the placebo group of a HPV16/18 vaccine trial. In HPV16-positive samples, HPV16 variants were identified by a reverse hybridization assay (RHA). Laser-capture micro-dissection (LCM) was performed for localized detection of HPV. HPV16 variants were determined in 47 women. Frequency of mixed HPV16 variant infections was lower (8.5%) than for multiple HPV genotypes (39.1%). Among 35 women having consecutive HPV16 variant-positive swabs, 32 (91.4%) had the same variant while in three (8.6%) women a change in variant(s) was observed. HPV16-positive WTS were obtained from 12 women having consecutive HPV16 variant-positive swabs. The same variant was present in WTS of 10 women, while two were negative. WTS of five women were histologically normal. A single HPV16 variant was detected in four women having CIN1-3, while additional HPV genotypes were found in three other women having CIN2 and CIN3. In the WTS of one woman with mixed genotypes, the HPV16 variant was assigned to a CIN2 lesion by LCM. HPV16 variant infections can be effectively studied in cervical swabs and tissue specimens by the HPV16 variant RHA. Multiple HPV16 variants in one woman are rare. The HPV16 genotype consistently detected in follow-up samples usually involves a persistent infection with the same variant.

Highlights

  • Human papillomavirus (HPV) is a DNA virus that infects cutaneous and mucosal epithelium and induces epithelial proliferation

  • More than 40 HPV genotypes have been detected in the anogenital region, and clinically most important are the oncogenic HPV genotypes (e.g., HPV16 and HPV18) which are involved in the development of high grade cervical intraepithelial neoplasias (CIN) and cervical cancer [1,2,3,4]

  • Materials from women in the placebo group were selected to rule out influence of the vaccine on the natural history of HPV16 variant infections

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Summary

Introduction

Human papillomavirus (HPV) is a DNA virus that infects cutaneous and mucosal epithelium and induces epithelial proliferation. HPV DNA has been detected in virtually all cervical cancer tissues [5], and persistent infection with an oncogenic. Vaccination against the most common oncogenic HPV genotypes, HPV16 and HPV 18, could prevent persistent infections of those genotypes and prevent the development of up to 70% of cervical cancers worldwide [8,9]. Diagnosis of HPV infections is based on detection of its genomic DNA in cervical cell samples or cervical biopsy specimens by molecular methods, such as liquid hybridization (e.g., the Hybrid Capture 2 assay, Qiagen) [10,11] or the polymerase chain reaction (PCR) [12,13]. Liquid hybridization detects HPV DNA by direct probe hybridization and can distinguish between groups of high-risk and low-risk HPV genotypes, but does not permit identification of individual genotypes [14]. PCR methods amplify parts of the HPV DNA genome, resulting in a high analytical sensitivity and specificity

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