Analysis of L1 gene sequence variations in high-risk and low-risk Human Papillomavirus (HPV) serotypes among indian women: implications for cervical cancer research
Keywords:
Human Papillomavirus, L1 Variants, Cervical cancer, Liquid based cytologyAbstract
Background and aim: Cervical cancer, ranking fourth globally and second in India among prevalent malignancies affecting women, poses a significant health challenge. Human Papillomavirus (HPV) infection, contributing significantly to cervical cancer, impacts about 5% of women worldwide annually. This study aims to comprehensively analyze sequence variations in L1 genes of high-risk (16, 18, 53, 58, 66, 73) and low-risk (6, 11, 70, 71, 84) HPV serotypes among Indian women. Methods: Liquid-Based Cytology (LBC) samples were systematically collected from diverse Indian regions. L1 variants were meticulously examined through Polymerase Chain Reaction (PCR) and DNA sequencing. Multalin software analyzed gene sequences, identifying alterations by comparing them with the NCBI Genebank's known HPV L1 sequences. Results: Mutation analysis revealed distinct alterations in various HPV serotypes, notably in HPV 6, 11, 16, 18, 31, 53, 58, 66, 70, 71, 73, and 84. High-risk serotypes 16 and 18, and low-risk serotypes 70 and 71, exhibited the highest number of mutations in the L1 region. Conclusions: This study provides crucial insights into genetic variations of prevalent HPV serotypes among Indian women. Identified mutations, particularly in high-risk HPV 16 and 18, and low-risk HPV 70 and 71, form a foundation for ongoing research in HPV-related cancers. These findings also open avenues for developing targeted HPV vaccines, promising advancements in cervical cancer prevention strategies.
References
Ferlay J, Soerjomataram I, Ervik M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5): E359-86. doi: 10.1002/ijc.29210.
Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013; 132(5):1133-45. doi: 10.1002/ ijc.27711.
Van Doorslaer K, Chen Z, Bernard HU, et al. Ictv Report C (2018) ICTV virus taxonomy profile: Papillomaviridae. J Gen Virol. 2018 ;99(8):989-90. doi: 10.1099/jgv.0.001105.
Carter JR, Ding Z, Rose BR. HPV infection and cervical disease: a review. Aust N Z J Obstet Gynaecol. 2011;1(2):103-8. doi: 10.1111/j.1479-828X.2010.01269.
Arbyn M, Tommasino M, Depuydt C, Dillner J. Are 20 human papillomavirus types causing cervical cancer? J Pathol. 2014;234(4):431-5. doi: 10.1002/path.4424.
Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev. 2003;16(1):1-17. doi: 10.1128/CMR.16.1.1-17.2003.
Zheng ZM, Baker CC. Papillomavirus genome structure, expression, and post-transcriptional regulation. Front Biosci. 2006;11:2286-302. doi: 10.2741/1971.
Chelimo C, Wouldes TA, Cameron LD, Elwood JM. Risk factors for and prevention of human papillomaviruses (HPV), genital warts and cervical cancer. J Infect. 2013;66(3):207-17. doi: 10.1016/j.jinf.2012.10.024.
Trottier H, Franco EL. The epidemiology of genital human papillomavirus infection. Vaccine. 2006 30;24 Suppl 1:S1-15. doi: 10.1016/j.vaccine.2005.09.054. PMID: 16406226.
Okunade KS. Human papillomavirus and cervical cancer. J Obstet Gynaecol. 2020;40(5):602-8. doi: 10.1080/01443615.2019.1634030.
Harper DM, DeMars LR. HPV vaccines - A review of the first decade. Gynecol Oncol. 2017;146(1):196-204. doi: 10.1016/j.ygyno.2017.04.004.
Gupta G, Glueck R, Patel PR. HPV vaccines: Global perspectives. Hum Vaccin Immunother. 2017;13(6):1-4. doi: 10.1080/21645515.2017.
Olsson SE, Restrepo JA, Reina JC, et al. Long-term immunogenicity, effectiveness, and safety of nine-valent human papillomavirus vaccine in girls and boys 9 to 15 years of age: Interim analysis after 8 years of follow-up. Papillomavirus Res. 2020;10:100203. doi: 10.1016/j.pvr.2020.100203.
Kapoor CS, Sharma M. Prevalence of HPV infection in reproductive aged female in Delhi NCR region. Clin Epidemiol Glob Health. 2020;8(2):612-5.doi.org/10.1016/j. cegh.2019.12.012.
World Health Organization. Strategic framework for the comprehensive prevention and control of cervical cancer in the Western Pacific Region 2023-2030:1-80.
Burki TK. India rolls out HPV vaccination. Lancet Oncol. 2023;24(4):e147. doi: 10.1016/S1470-2045(23)00118-3.
Viveros-Carreño D, Fernandes A, Pareja R. Updates on cervical cancer prevention. Int J Gynecol Cancer. 2023;33(3):394-402. doi: 10.1136/ijgc-2022-003703.
Bosch FX, Broker TR, Forman D, et al. Authors of the ICO Monograph ‘Comprehensive Control of HPV Infections and Related Diseases’ Vaccine Volume 30, Supplement 5, 2012. Comprehensive control of human papillomavirus infections and related diseases. Vaccine. 2013; 22;31 Suppl 8(0 8):I1-31. doi: 10.1016/j.vaccine.2013.07.026.
Shen-Gunther J, Cai H, Zhang H, Wang Y. Abundance of HPV L1 Intra-Genotype Variants With Capsid Epitopic Modifications Found Within Low- and High-Grade Pap Smears With Potential Implications for Vaccinology. Front Genet. 2019; 24;10:489. doi: 10.3389/fgene.2019.00489.
Pangarkar MA. The Bethesda System for reporting cervical cytology. Cytojournal. 2022;19:28. doi: 10.25259/CMAS_03_07_2021.
Ikenberg H, Bergeron C, Schmidt D, et al. PALMS Study Group. Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study. J Natl Cancer Inst. 2013;105(20):1550-7. doi: 10.1093/jnci/djt235.
Conceição T, Braga C, Rosado L, Vasconcelos MJM. A Review of Computational Methods for Cervical Cells Segmentation and Abnormality Classification. Int J Mol Sci. 2019;20(20):5114. doi: 10.3390/ijms20205114.
Zhao M, Wu Q, Hao Y, Hu J, Gao Y, Zhou S, Han L. Global, regional, and national burden of cervical cancer for 195 countries and territories, 2007-2017: findings from the Global Burden of Disease Study 2017. BMC Womens Health. 2021;21(1):419. doi: 10.1186/s12905-021-01571-3.
Sharma K, Kathait A, Jain A, et al. Higher prevalence of human papillomavirus infection in adolescent and young adult girls belonging to different Indian tribes with varied socio-sexual lifestyle. PLoS One. 2015;10(5):e0125693. doi: 10.1371/journal.pone.0125693.
de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020;8(2):e180-e90. doi: 10.1016/S2214-109X(19)30488-7.
Ardekani A, Sepidarkish M, Mollalo A, et al. Worldwide prevalence of human papillomavirus among pregnant women: A systematic review and meta-analysis. Rev Med Virol. 2023;33(1):e2374. doi: 10.1002/rmv.2374.
Yue Y, Yang H, Wu K, et al. Genetic variability in L1 and L2 genes of HPV-16 and HPV-58 in Southwest China. PLoS One. 2013;8(1):e55204. doi: 10.1371/journal. pone. 0055204.
Chang CH, Chen TH, Hsu RC, Chou PH, Yang JJ, Hwang GY. The prevalence of HPV-18 and variants of E6 gene isolated from cervical cancer patients in Taiwan. J Clin Virol. 2005;32(1):33-7. doi: 10.1016/j.jcv.2004.06.011.
St Laurent J, Luckett R, Feldman S. HPV vaccination and the effects on rates of HPV-related cancers. Curr Probl Cancer. 2018;42(5):493-506. doi: 10.1016/j. currproblcancer. 2018.06.004.
Olivas AD, Barroeta JE, Lastra RR. Overview of Ancillary Techniques in Cervical Cytology. Acta Cytol. 2023;67(2):119-28. doi: 10.1159/000528931.
Orlando G, Beretta R, Fasolo MM, et al. Anal HPV genotypes and related displasic lesions in Italian and foreign born high-risk males. Vaccine. 2009;29;27 Suppl 1:A24-9. doi: 10.1016/j.vaccine.2008.12.026.
García-Martínez CM, Calle-Gómez I, López-Hidalgo J, et al, C. Role of Low-Risk HPV PCR Monoinfection in Screening for HSIL and Anal Cancer in Men Who Have Sex with Men Living with HIV. Int J Mol Sci. 2023;24(6):5642. doi: 10.3390/ijms24065642.
Bernard HU, Calleja-Macias IE, Dunn ST. Genome variation of human papillomavirus types: phylogenetic and medical implications. Int J Cancer. 2006;118(5):1071-6. doi: 10.1002/ijc.21655.
Chen Z, Schiffman M, Herrero R, et al, Evolution and taxonomic classification of human papillomavirus 16 (HPV16)-related variant genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67. PLoS One. 2011;6(5):e20183. doi: 10.1371/journal.pone.0020183.
Yu D, Chen Y, Wu S, Wang B, Tang YW, Li L. Simultaneous detection and differentiation of human papillomavirus genotypes 6, 11, 16 and 18 by AllGlo quadruplex quantitative PCR. PLoS One. 2012;7(11):e48972. doi: 10.1371/journal. pone.0048972.
Loyo M, Li RJ, Bettegowda C, et al. Lessons learned from next-generation sequencing in head and neck cancer. Head Neck. 2013;35(3):454-63. doi: 10.1002/hed.23100.
Chen Z, Jing Y, Wen Q, et al. L1 and L2 gene polymorphisms in HPV-58 and HPV-33: implications for vaccine design and diagnosis. Virol J. 2016;13(1):167. doi: 10.1186/s12985-016-0629-9.
Namvar A, Bolhassani A, Javadi G, et al. In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine. Sci Rep.2019; 9:15225. doi:10.1038/s41598-019-51679-8
Wentzensen N, Schiffman M, Dunn T, et al. Multiple human papillomavirus genotype infections in cervical cancer progression in the study to understand cervical cancer early endpoints and determinants. Int J Cancer. 2009;125(9):2151-8. doi: 10.1002/ijc.24528.
Chen D, McKay JD, Clifford G, et al. Genome-wide association study of HPV seropositivity. Hum. Mol. Genet. 2011;20(23):4714-23. doi:10.1038/ng.3685.
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