Predominance of genomically defined A lineage of HPV16 over D lineage in Indian patients from eastern India with squamous cell carcinoma of the cervix in association with distinct oncogenic phenotypes

Paramita Mandal; Bornali Bhattacharjee; Shrinka Sen; Amrapali Bhattacharya; Sweta Sharma Saha; Rahul Roy Chowdhury; Nidhu Ranjan Mondal; Biman Chakrabarty; Tanmay Chatterjee; Sudipta Roy; Sharmila Sengupta

doi:10.1016/j.tranon.2021.101256

Predominance of genomically defined A lineage of HPV16 over D lineage in Indian patients from eastern India with squamous cell carcinoma of the cervix in association with distinct oncogenic phenotypes

Transl Oncol. 2022 Jan;15(1):101256. doi: 10.1016/j.tranon.2021.101256. Epub 2021 Oct 27.

Affiliations

¹ National Institute of Biomedical Genomics, P.O.: N.S.S., Kalyani, West Bengal 741251, India; Biomedical Genetics Laboratory, Department of Zoology, The University of Burdwan, Purba Burdwan, West Bengal 713104, India.
² National Institute of Biomedical Genomics, P.O.: N.S.S., Kalyani, West Bengal 741251, India; Amity Institute of Biotechnology, Amity University Kolkata, Kolkata, India. Electronic address: bbhattacharjee@kol.amity.edu.
³ National Institute of Biomedical Genomics, P.O.: N.S.S., Kalyani, West Bengal 741251, India; Department of Medical Genetics, University of British Columbia, 4500 Oak Street, Vancouver, British Columbia V6H 3N1, Canada.
⁴ National Institute of Biomedical Genomics, P.O.: N.S.S., Kalyani, West Bengal 741251, India; DBT-NIDAN Kendra on Rare Genetic Diseases, N. R. S. Medical College and Hospital, 138, A. J. C. Bose Road, Kolkata 700014, India.
⁵ National Institute of Biomedical Genomics, P.O.: N.S.S., Kalyani, West Bengal 741251, India; Translational and Clinical Research Institute, Faculty of Medical Sciences, Centre for Cancer, Newcastle University, NE2 4HH, UK.
⁶ Saroj Gupta Cancer Centre and Research Institute, Kolkata, India.
⁷ AMRI Group of Hospitals, Kolkata, India.
⁸ National Institute of Biomedical Genomics, P.O.: N.S.S., Kalyani, West Bengal 741251, India. Electronic address: ssg1@nibmg.ac.in.

Abstract

Human papillomavirus type-16 (HPV16) is classified into lineages, A, B, C and D and 10 sub-lineages portraying variable infectivity, persistence, and cytological outcomes, however, with geographical variations. Our objective was to delineate the distinctive features of lineages among cervical squamous cell carcinoma (SCC) in the eastern region of India. A total of 145 SCC cases and 24 non-malignant specimens, harboring episomal HPV16, were included. The presence of higher proportion of lineage A over D was observed among SCC cases (86.89% A1, 8.97% D1 and 4.14% D2), while only A1 sub-lineage viruses were found among control specimens. Among the A1 viruses, an association of variants in the E5 (Y44L, I65V), E6 (L83V) genes and LCR: C7577T with SCC, with combined Odd's ratio (95% CI) of 20.5(4.61-91.25) was observed. Network analyses revealed the presence of 10 clades of lineage A viruses comprising of 64 HPV16 genomes harboring the risk alleles. High episomal HPV16 DNA copy numbers (adjusted p-value= 0.0271) and E7 mRNA expression (p-value=0.000017) predominated in SCC with lineage A, over D. Our study highlights the distinctive modalities of oncogenicity among different HPV16 lineages.

Keywords: Cervical cancer; E7 expression; Episomal HPV16 lineages; Phylogenetic networks; Viral copy numbers.