Abstract
BackgroundHuman papillomavirus (HPV) type 16 accounts for a larger share of cervical cancer and has been a major health problem worldwide for decades. The progression of initial infection to cervical cancer has been linked to viral sequence properties; however, the role of HPV16 variants in the risk of cervical carcinogenesis, especially with longitudinal follow-up, is not fully understood in China.MethodsWe aimed to investigate the genetic variability of HPV16 E6 and E7 oncogenes in isolates from cervical exfoliated cells. Between December 2012 and December 2014, a total of 310 single HPV16-positive samples were selected from women living in the Taizhou area, China. Sequences of all E6 and E7 oncogenes were analysed by PCR-sequencing assay. Detailed sequence comparison, genetic heterogeneity analyses and maximum-likelihood phylogenetic tree construction were performed with BioEdit Sequence Alignment Editor and MEGA X software. Data for cytology tests and histological diagnoses were obtained from our Taizhou Area Study with longitudinal follow-up for at least 5 years. The relationship between HPV16 variants and cervical carcinogenesis risk was analysed by the chi-square test or Fisher’s exact test.ResultsIn this study, we obtained 64 distinct variation patterns with the accession GenBank numbers MT681266-MT681329. Phylogenetic analysis revealed that 98.3% of HPV16 variants belong to lineage A, in which the A4 (Asian) sublineage was dominant (64.8%), followed by A2 (12.1%), A1 (11.4%), and A3 (10.0%). The A4 (Asian) sublineage had a higher risk of CIN2+ than the A1–3 (European) sublineages (OR = 2.69, 95% CI = 1.04–6.97, P < 0.05). Furthermore, nucleotide variation in HPV16 E6 T178G is associated with the development of cervical cancer.ConclusionThese data could provide novel insights into the role of HPV16 variants in cervical carcinogenesis risk in China.
Highlights
Human papillomavirus (HPV) type 16 accounts for a larger share of cervical cancer and has been a major health problem worldwide for decades
We investigated the genetic variants in HPV16 E6 and E7 oncoprotein-encoding genes and their involvement in cervical carcinogenesis in the Taizhou area, Southeast China
The HPV16 E6 and E7 genes were amplified by using specific primers for E6 and E7, 16E6E7_F 5′-ACTAAGGGCGTA ACCGAAAT-3′ and 16E6E7_R 5′-TGCAGTAAAC AACGCAT-3′, which were designed using Primer Premier 5 according to the prototype HPV16 reference sequence (GenBank accession number K02718)
Summary
Human papillomavirus (HPV) type 16 accounts for a larger share of cervical cancer and has been a major health problem worldwide for decades. The progression of initial infection to cervical cancer has been linked to viral sequence properties; the role of HPV16 variants in the risk of cervical carcinogenesis, especially with longitudinal follow-up, is not fully understood in China. HPV16 genetic variants can be divided into four main phylogenetic lineages: A (sublineages A1–4), B (sublineages B1–4), C (sublineages C1–4) and D (sublineages D1–4) [13, 14]. We investigated the genetic variants in HPV16 E6 and E7 oncoprotein-encoding genes and their involvement in cervical carcinogenesis in the Taizhou area, Southeast China
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