Analysis of Human Papillomavirus (HPV) 16 Variants Associated with Cervical Infection in Italian Women

Marianna Martinelli,Andrea Piana,Narcisa Muresu,Rosario Musumeci,Giovanni Sotgiu,Antonio Cossu,Clementina Cocuzza,Chiara Villa,Federica Perdoni,Romina Combi

doi:10.3390/ijerph17010306

Abstract

This study aims to evaluate HPV16 variants distribution in a population of Italian women living in two different regions (Lombardy and Sardinia) by sequence analyses of HPV16-positive cervical samples, in order to reconstruct the phylogenetic relationship among variants to identify the currently circulating lineages. Analyses were conducted starting from DNA isolated from 67 HPV16-positive cervical samples collected from two different Italian centres (31 from Lombardy and 36 from Sardinia) of women with normal and abnormal cervical cytology. The entire long control region (LCR) and 300 nt of the E6 gene was sequenced to identify intra-type variants. Sequence comparison and phylogenetic analysis were made using a distance-based neighbour joining method (NJ) and Kimura two-parameter model. Data obtained reported that Italian sequences mainly belonged to the European lineage, in particular sublineage A2. Only five sequences clustered in non-European branches: two in North American lineage (sublineage D1), two in African-1 (sublineage B1) and one in African-2. A new 27 nucleotide duplication in the central segment of the LCR region was found in a sequence obtained from a sample isolated in Sardinia. A predominance of European variants was detected, with some degree of variability among the studied HPV16 strains. This study contributes to the implementation of data regarding the molecular epidemiology of HPV16 variants.

Highlights

Human papillomavirus (HPV), recognized as the etiological agent of genital and extra-genital cancers, is a highly conserved circular double-stranded DNA virus [1]
The aim of the study was to investigate the HPV16 variant distribution in cervical samples collected from women living in two different Italian regions (i.e., Lombardy and Sardinia) and to assess the phylogenetic relationships among variants
This study was conducted by analyzing DNA isolated from HPV16-positive cervical samples of women with normal and abnormal cytology

Summary

Introduction

Human papillomavirus (HPV), recognized as the etiological agent of genital and extra-genital cancers, is a highly conserved circular double-stranded DNA virus [1]. ~8000 bases in length and is divided into three functional regions: a non-coding upstream regulatory region (URR), known as the long control region (LCR), containing regulatory elements for viral replication and transcription; an early region (E1, E2, E4–E7 genes) encoding core viral proteins (e.g., E6 and E7 proteins can cause transformation of the host cell); a late region, encoding L1 and L2 capsid proteins responsible for the viral DNA packaging and assembling in an icosahedral structure [2]. >200 HPV types have been identified based on >10% nucleotide diversity of L1 gene [3,4]. Since HPV genome replication relies on high-fidelity DNA polymerases of the host. Public Health 2020, 17, 306; doi:10.3390/ijerph17010306 www.mdpi.com/journal/ijerph

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