Abstract
BackgroundHPV 16 is the cause of cervical carcinoma, but only a small fraction of women with HPV infection progress to this pathology. Besides persistent infection and HPV integration, several studies have suggested that HPV intratype variants may contribute to the development of cancer. The purpose of this study was to investigate the nucleotide variability and phylogenetically classify HPV 16 E6 variants circulating over a period of 16 years in women from Southern Mexico, and to analyze its association with precursor lesions and cervical carcinoma.MethodsThis study was conducted in 330 cervical DNA samples with HPV 16 from women who were residents of the State of Guerrero, located in Southern Mexico. According of cytological and/or histological diagnosis, samples were divided into the following four groups: no intraepithelial lesion (n = 97), low-grade squamous intraepithelial lesion (n = 123), high-grade squamous intraepithelial lesion (n = 19) and cervical carcinoma (n = 91). HPV 16 E6 gene was amplified, sequenced and aligned with reference sequence (HPV 16R) and a phylogenetic tree was constructed to identify and classify HPV 16 variants. Chi squared was used and data analysis and statistics were done with SPSS Statistics and STATA softwares.ResultsTwenty seven HPV 16 E6 variants were detected in women from Southern Mexico, 82.12% belonged to the EUR, 17.58% to AA1 and 0.3% to Afr2a sublineages. The most common was E-G350 (40%), followed by E-prototype (13.03%), E-C188/G350 (11.82%), AA-a (10.61%), AA-c (6.07%) and E-A176/G350 (5.15%). Eight new E6 variants were found and 2 of them lead to amino acid change: E-C183/G350 (I27T) and E-C306/G350 (K68T). The HPV 16 variant that showed the greatest risk of leading to the development of CC was AA-a (OR = 69.01, CI = 7.57-628.96), followed by E-A176/G350 (OR = 39.82, CI = 4.11-386.04), AA-c (OR = 21.16, CI 2.59-172.56), E-G350 (OR = 13.25, CI = 2.02-87.12) and E-C188/G350 (OR = 10.48, CI = 1.39-78.92).ConclusionsThe variants more frequently found in women with cervical carcinoma are E-G350, AA-a, AA-c, E-C188/G350 and E-A176/G350. All of them are associated with the development of cervical carcinoma, however, AA-a showed the highest association. This study reinforces the proposal that HPV 16 AA-a is an oncogenic risk for cervical carcinoma progression in Mexico.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-015-0242-3) contains supplementary material, which is available to authorized users.
Highlights
HPV 16 is the cause of cervical carcinoma, but only a small fraction of women with HPV infection progress to this pathology
HPV 16 variants have been classified into 4 major lineages and 9 sublineages based on common LCR and E6 single polymorphisms: (1) European-Asian (EAS), including European (EUR) and Asian (As) sublineages; (2) African 1 (AFR1), including Afr1a and Afr1b sublineages; (3) African 2 (AFR2), including Afr2a and Afr2b sublineages; and (4) Asian American/North American (AA/NA), including Asian American 1 (AA1), Asian American 2 (AA2) and North American (NA) sublineages [12]
The phylogenetic analysis showed that the E6 variants found belong to EUR, AA1 and Afr2a sublineages
Summary
HPV 16 is the cause of cervical carcinoma, but only a small fraction of women with HPV infection progress to this pathology. The purpose of this study was to investigate the nucleotide variability and phylogenetically classify HPV 16 E6 variants circulating over a period of 16 years in women from Southern Mexico, and to analyze its association with precursor lesions and cervical carcinoma. Infection by high risk human papillomavirus (HR-HPV) is necessary for the development of cervical carcinoma (CC) [1] and HPV 16 is the cause of more than half of CC worldwide [2]. A small fraction of women with HPV infection may progress to cervical carcinoma; the factors that favor this progression are still poorly understood. HPV 16 variants have been classified into 4 major lineages and 9 sublineages based on common LCR and E6 single polymorphisms: (1) European-Asian (EAS), including European (EUR) and Asian (As) sublineages; (2) African 1 (AFR1), including Afr1a and Afr1b sublineages; (3) African 2 (AFR2), including Afr2a and Afr2b sublineages; and (4) Asian American/North American (AA/NA), including Asian American 1 (AA1), Asian American 2 (AA2) and North American (NA) sublineages [12]
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