High grade cervical lesions are caused preferentially by non‐European variants of HPVs 16 and 18

Abstract

The intratypic variability of HPVs 16 and 18 has been extensively studied and has been used as an important tool in epidemiological studies of viral transmission, persistence and progression to clinically relevant cervical lesions. Infections by non-European variants of HPVs 16 and 18 are associated with an increased risk for the development of high grade squamous intraepithelial lesions (HSIL). Our aim was to correlate the intratypic molecular variability of both HPV types and risk of persistent infection and lesion outcome in a cohort study conducted in Brazil. We characterized molecular variants of HPV types 16 and 18 by sequencing a fragment of the LCR, and of the E6 and L1 genes, for HPV-16 variants only. For both types, European variants composed the most prevalent and diverse group. Persistent infections with HPV-18 were associated with continuous detection of European variants. However, risk for simultaneous detection of HSIL and HPV DNA was higher in women harboring non-European variants of HPV-16. The same trend was observed with HSIL detected during follow-up. Our study confirms the association between non-European variants and risk of cervical neoplasia, and highlights the importance of their geographic distribution for cervical cancer risk assessment. ' 2007 Wiley-Liss, Inc.Key words: human papillomavirus; molecular variants; oncogenic potential; cohort study; cervical neoplasia More than 120 different human papillomavirus (HPV) genotypes associated with infections in humans have been described, of which approximately 40 infect the anogenital area. Nearly 20 of these are classified as high-risk HPV types (HR-HPV) due to their association with cancer. In particular, HPVs 16 and 18 are the most common high-risk types in cancer biopsies, worldwide. 1 Their oncogenic potential has been demonstrated both in vitro and in vivo. 2 Nevertheless, only a minority of women infected with HPVs 16 and 18 develop neoplastic lesions. 3,4 Intratypic molecular variants of HPVs are characterized by differences in nucleotide sequence from the prototypic L1 gene of less than 2%. 5 Recently, full genome analysis of HPV-16 isolates revealed that 4% of the sequence is variable. 6 Moreover, these authors described a 9.9% amino acid variability within the eight HPV genes of the different HPV-16 molecular variants studied. The nucleotide variability of HPVs 16 and 18 has been extensively studied, and several molecular variants have been described on the basis of their geographical distribution. 7-9 Studies conducted in multiethnic populations have shown the association between Asian-American or other non-European variants of HPVs 16 and 18 and increased risk of persistent infection and development of cervical lesion. 4,10-13 Specific variants of HPVs 16 and 18 seem to be associated also with certain histopathological features of cervical neoplastic lesions. 10,14,15 In one study, Asian-American variants of both HPVs 16 and 18 were associated with squamous cell carcinomas and adenocarcinomas, while European variants were assoc...

Human Papillomavirus Type 16 Variant Analysis of E6, E7, and L1 Genes and Long Control Region in Identification of Cervical Carcinomas in Patients in Northeast China

“…HPV 16 variants, which vary by Յ2% from HPV 16 prototype nucleotide sequences, have been identified as the following six phylogenetic branches: European (E), Asian (As), Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and northern American (NA) variants (18,52). Several researchers had reported correlations between specific HPV 16 variants and persistent viral infection, followed by the development of malignant lesions (3,4,16,37,43,49,50). Non-European variants were found to be associated with an excess risk of cervical cancer (37).…”

“…Several researchers had reported correlations between specific HPV 16 variants and persistent viral infection, followed by the development of malignant lesions (3,4,16,37,43,49,50). Non-European variants were found to be associated with an excess risk of cervical cancer (37). These variants had been found to show different geographic distributions, while some sequence variations had oncogenic potentials.…”

Unique variants of human papillomavirus genotypes 52 and 58 and risk of cervical neoplasia

“…Then, the PCR product was carried out by using a commercial HPV blot (EasyChip V R HPV Genotyping Array, King Car, Taiwan). The blot detects 39 types including HPV 6,11,16,18,26,31, …”

“…11,14,15 Recent longitudinal studies have documented the association between certain variants of HPV 16 and 18 and the risk of cervical neoplasia. 16,17 The intratypic variants of HPV 16 and 18 have been studied extensively, and data on the E6, E7 and LCR genetic variations of HPV 52 or 58 have also been reported previously. [18][19][20][21][22][23] Variant lineages of carcinogenic HPV types were determined (RD Burk; personal communication) in a population-based prospective study and their associations with viral persistence and/or risk of CIN3/ CIS and cancer (CIN3þ) were evaluated using a nested casecontrol study design.…”

Evaluation of the genetic variability of human papillomavirus type 52

“…This difference confers each variant a biologically distinct characterization and pathogenic risks (6). HPV-52 is phylogenetically related to HPV-16 (7), whose variants could be divided into Asian-American, African and European lineages, whose carcinogenic risks have been extensively studied (8,9). Similarly, the variants of HPV-52 could be classified as Asian and European lineages (10), with a mean sequence difference of 1.8-2.0% (11).…”