Abstract
BackgroundWorldwide, cervical cancer is the second most common cancer in women. High-risk human papillomavirus (HPV) play a crucial role in the etiology of cervical cancer and the most prevalent genotype is HPV16. HPV 16 intratypic variants have been reported to differ in their prevalence, biological and biochemical properties. The present study was designed to analyze and identify HPV type 16 E6 variants among patients with cervical cancer in Morocco.MethodsA total of 103 HPV16 positive samples were isolated from 129 cervical cancer cases, and variant status was subsequently determined by DNA sequencing of the E6 gene.ResultsIsolates from patients were grouped into the European (E), African (Af) and North-American (NA1) phylogenetic clusters with a high prevalence of E lineage (58.3%). The Af and NA1 variants were detected in 31.1% and 11.6% of the HPV16 positive specimens, respectively, whereas, only 3% of cases were prototype E350T. No European-Asian (EA), Asian (As) or Asian-American (AA) variants were observed in our HPV16-positive specimens. At the amino acid level, the most prevalent non-synonymous variants were L83V (T350G), H78Y (C335T), E113D (A442C), Q14D (C143G/G145T) and R10I (G132T), and were observed respectively in 65%, 41.8%, 38.8%, 30.1% and 23.3% of total samples.Moreover, HPV16 European variants were mostly identified in younger women at early clinical diagnosis stages. Whereas, HPV16 Af variants were most likely associated with cervical cancer development in older women with pronounced aggressiveness.ConclusionThis study suggests a predominance of E lineage strains among Moroccan HPV 16 isolates and raises the possibility that HPV16 variants have a preferential role in progression to malignancy and could be associated with the more aggressive nature of cervical cancer.
Highlights
Worldwide, cervical cancer is the second most common cancer in women
In the present study entirely done in Morocco, we have examined whether naturally occurring sequence variations in the HPV16 E6 gene exist in cervical cancer from Moroccan subjects with human papillomavirus (HPV) 16 infection
Histopathological data The pathological analysis revealed the predominance of Squamous Cell Carcinoma (SCC) that represents 96.89% of cases (125/129)
Summary
Cervical cancer is the second most common cancer in women. High-risk human papillomavirus (HPV) play a crucial role in the etiology of cervical cancer and the most prevalent genotype is HPV16. Variants of the HPV16 genome in cervical carcinoma, precancerous lesions and normal or inflammatory cervical cases, from different geographical areas have been classified into phylogenetic lineages as European (E), Asian (As), Asian-American (AA), African -1 and -2 (Af1 and Af2), and North American (NA1) [8,12,13]. Multiple studies have shown that HPV16 variants differ in risk for progression to high grade intraepithelial lesions [14,15,16], in their association with the development of cervical cancer [15,17,18,19], viral persistence [17,20,21,22,23,24,25,26] and the frequency of recurrence of cervical disease [15]
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