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

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

doi:10.1016/j.tranon.2021.101256

Cited by 5 publications

(5 citation statements)

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“…Of these lineages, A1 sub-lineage was predominant among women with cervical carcinoma [25]. The previous studies in India revealed the HPV 16 A1 (European) sublineage was predominant among cervical carcinoma patients compared to D1 (North American) and D2 (Asian-American-1) [15,25]. The current study found sub-lineages A1, A2, and D1 to be prevailing in South Andaman.…”

Section: Discussionsupporting

confidence: 51%

“…A study conducted in Eastern India revealed the existence of A1, D1 and D2 lineages. Of these lineages, A1 sub-lineage was predominant among women with cervical carcinoma [25]. The previous studies in India revealed the HPV 16 A1 (European) sublineage was predominant among cervical carcinoma patients compared to D1 (North American) and D2 (Asian-American-1) [15,25].…”

Section: Discussionmentioning

confidence: 89%

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Distribution of Human Papillomavirus Genotypes among the Women of South Andaman Island, India

Parvez,

Vijayachari,

Saha

et al. 2023

Diagnostics

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Background: Human Papillomavirus (HPV) causes various types of cancer in both men and women. Woman with HPV infection has a risk of developing invasive cervical cancer. Globally, HPV 16 and 18 were predominant. This study aims to find the distribution of various HPV types in South Andaman. Methods: A cross-sectional study was conducted among women in South Andaman, where cervical scrapes were collected after collecting written informed consent. Detection of HPV genotypes was carried out by using a PCR assay. Further, sequencing analysis was performed using MEGA11 to identify various genotypes in this territory. Result: Of these 1000 samples, 32 were positive for HR-HPV 16, and four were positive for HR-HPV 18. Fifteen HPV genotypes were detected using molecular evolutionary analysis. Six cases were identified with multiple genotypes. The most prevalent genotype is HPV 16 which belongs to Lineage-A and sub-lineage A2. HPV 18 identified in South Andaman belonged to the lineage A1 to A5. Discussion: Various HPV types were identified among women in South Andaman. Global burden of cervical cancer associated with various HPV sub-lineages. HPV-16 A1 sub-lineage was globally widespread, whereas sub-lineages A1, A2 and D1 prevailed in South Andaman. Conclusions: HR-HPV identified in this study enlightens the importance of HPV vaccination among women in remote places. These findings will help to strengthen public health awareness programs and prevention strategies for women in remote areas.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 89%

Distribution of Human Papillomavirus Genotypes among the Women of South Andaman Island, India

Parvez,

Vijayachari,

Saha

et al. 2023

Diagnostics

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“…HPV-16 is divided into genetic sub-lineages A1–4, B1–4, C1–4 and D1–4. The distribution of the lineages varies geographically and ethnically [ 38 ]. Globally, variants of HPV-16 sub-lineages A1–A3 are predominantly found in Europe, A4 sub-lineage in Asia, B and C lineages exclusively in Africa, and D lineage most common in South/Central America [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic variation of E6 and E7 genes of human papillomavirus type 16 from central China

Li,

Yang,

Zhang

et al. 2023

Virol J

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Background Persistent high-risk human papillomavirus (HR-HPV) infection is an important factor in the development of cervical cancer, and human papillomavirus type 16 (HPV-16) is the most common HR-HPV type worldwide. The oncogenic potential of HPV-16 is closely related to viral sequence variation. Methods In order to clarify the variant characteristics of HPV-16 E6 and E7 genes in central China, E6 and E7 sequences of 205 HPV‐16 positive samples were amplified by polymerase chain reaction. PCR products of E6 and E7 genes were further sequenced and subjected to variation analysis, phylogenetic analysis, selective pressure analysis and B-cell epitope prediction. Results Twenty-six single nucleotide variants were observed in E6 sequence, including 21 non-synonymous and 5 synonymous variants. Twelve single nucleotide variants were identified in E7 sequence, including 6 non-synonymous and 6 synonymous variants. Four new variants were found. Furthermore, nucleotide variation A647G (N29S) in E7 was significantly related to the higher risk of HSIL and cervical cancer. Phylogenetic analysis showed that the E6 and E7 sequences were all distributed in A lineage. No positively selected site was found in HPV-16 E6 and E7 sequences. Non-conservative substitutions in E6, H31Y, D32N, D32E, I34M, L35V, E36Q, L45P, N65S and K75T, affected multiple B-cell epitopes. However, the variation of E7 gene had little impact on the corresponding B-cell epitopes (score < 0.85). Conclusion HPV-16 E6 and E7 sequences variation data may contribute to HR-HPV prevention and vaccine development in Jingzhou, central China.

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“…Earlier studies from our laboratory have revealed heterogeneity of CaCx with respect to viral [11,12] as well as host factors [13,14]. Further on, in this study, we aimed to dissect out tumor immune heterogeneity, if any, considering the expression status of a large majority of immune pathway genes and characterise these tumors with respect to host immune-related factors, cancer-associated phenotypes and viral factors.…”

Section: Introductionmentioning

confidence: 98%

Identification of HPV16 positive cervical cancer subsets characterized by divergent immune and oncogenic phenotypes with potential implications for immunotherapy

Ghosh

Sinha

et al. 2023

TUB

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BACKGROUND: Cervical cancers (CaCx), like many other cancer types, portray high molecular heterogeneity that affects response to therapy, including immunotherapy. In India and other developing countries, CaCx mortality rates are very high because women report to the clinics with advanced cancers in absence of organized screening programs. This calls for implementation of newer therapeutic regimens for CaCx, like immunotherapy, which is again not used commonly in such countries. OBJECTIVE: Therefore, we focused on dissecting tumour immune heterogeneity, if any, identify immune gene-based biomarkers of heterogeneity and subsets of such cancers with the potential for immunotherapy. We also attempted to characterize the cancer-associated phenotypes of such subsets, including viral load, to decipher the relationship of tumour immunogenicity with oncogenicity. METHODS: Employing RNA-seq analysis of 44 HPV16 positive CaCx patients, immune subtypes were identified by unsupervised hierarchical clustering of global immune-gene expression profiles. Proportions of tumor infiltrating immune cells in the tumor milieu were estimated, employing Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), using gene expression data from RNA-seq. The oncogenic phenotypes of the immune subtypes of CaCx were deciphered through differential gene expression (DEGs) and pathway enrichment analysis. Viral load was estimated through TaqMan-based qRT-PCR analysis. RESULTS: Analysis revealed the presence of two immune subtypes of CaCx, A (26/44; 59.09%) and B (18/44; 40.90%). Compared to Subtype-A, Subtype-B portrayed overexpression of immune genes and high infiltration of immune cells, specifically CD8+ T cells (p < 0.0001). Besides, a significant correlation between PD-1 and PD-L1 co-expression among Subtype-B, as opposed to Subtype-A, confirmed the interactive roles of these immune checkpoint molecules in Subtype B. Stepwise discriminant analysis pin-pointed ten immune-genes that could classify 100% of the patients significantly (p < 0.0001) into the two immune subtypes and serve as potential biomarkers of CaCx immunity. Differential gene expression analysis between the subtypes unveiled that Subtype-B was more biologically aggressive than Subtype-A, reflecting loss of structural integrity and promotion of cancer progression. The viral load was significantly lower in Subtype-B (average viral load = 10.74/100 ng of genomic DNA) compared to Subtype-A (average viral load = 14.29/100 ng of genomic DNA). Thus viral load and the ten-gene panel underscore their association with immunogenicity and oncogenicity. CONCLUSION: Our study provides strong evidence that only a subset, about 41% of HPV16 positive CaCx patients in India, portray immune enrichment of the tumor milieu coupled with aggressive phenotypes. Such subtypes are therefore likely to benefit through checkpoint molecule-based or tumor infiltrating lymphocyte-based immunotherapy, which could be a leap forward in tackling aggressive forms of such CaCx in India and other developing countries.

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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

Cited by 5 publications

References 57 publications

Distribution of Human Papillomavirus Genotypes among the Women of South Andaman Island, India

Distribution of Human Papillomavirus Genotypes among the Women of South Andaman Island, India

Genetic variation of E6 and E7 genes of human papillomavirus type 16 from central China

Identification of HPV16 positive cervical cancer subsets characterized by divergent immune and oncogenic phenotypes with potential implications for immunotherapy

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