Human papillomavirus type 16 variant analysis of E6, E7, and L1 genes and long control region in biopsy samples from cervical cancer patients in north India.
High-risk human papillomaviruses (HPVs), particularly HPV types 16 and 18 (HPV-16 and HPV-18, respectively), play a cardinal role in the etiology of cervical cancer. The most prevalent type, HPV-16, shows intratypic sequence variants that are known to differ in oncogenic potential and geographic distribution. This study was designed to analyze sequence variations in E6, E7, and L1 genes and the LCR (for long control region) of HPV-16 in cervical cancer patients to identify the most prevalent and novel HPV-16 variants and to correlate them with the severity of the disease. Cervical biopsies from 60 HPV-16-positive cancer cases were analyzed by PCR and DNA sequencing. The most frequently observed variations were T350G (100%) in E6, T789C (87.5%) in E7, A6695C (54.5%) in L1, and G7521A (91.1%) in the LCR. In addition, only one novel variant (T527A) in E6 and four new variants each in L1 (A6667C, A6691G, C6906T, and A6924C) and in the LCR (C13T, A7636C, C7678T, and G7799A) were identified. While E7 was found to be highly conserved, the variant 350G of E6 was the most prevalent in all of the histopathological grades. The majority of LCR variants were found at the YY1 transcription factor binding sites. Interestingly, a complete absence of the Asian lineage and a high prevalence of European lineages in E6, E7, L1, and the LCR (85, 86.7, 67.7, and 63.3%, respectively) indicate a possible epidemiological linkage between Europe and India with regard to the dissemination of HPV-16 infections in India.
Pande
Shailja
S
Division of Molecular Oncology, Institute of Cytology and Preventive Oncology, I-7, Sector 39, Noida 201301, India.
Jain
Neeraj
N
Prusty
Bhupesh K
BK
Bhambhani
Suresh
S
Gupta
Sanjay
S
Sharma
Rajyashri
R
Batra
Swaraj
S
Das
Bhudev C
BC
D001483:Base Sequence; D001706:Biopsy; D036022:Capsid Proteins / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D052162:Human papillomavirus 16 / Q000145:classification* / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007194:India; D019901:Locus Control Region / Q000235:genetics; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology*
D036022:Capsid Proteins; D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; C063317:L1 protein, Human papillomavirus type 16