Association of p16 (CDKN2A) polymorphisms with the development of HPV16‐related precancerous lesions and cervical cancer in the Greek population

Tsakogiannis, D.; Moschonas, George D.; Bella, Evangelia; Kyriakopoulou, Zaharoula; Amoutzias, Grigoris D.; Dimitriou, Tilemachos G.; Kottaridi, Christine; Markoulatos, Panayotis

doi:10.1002/jmv.24996

Cited by 11 publications

(9 citation statements)

References 37 publications

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“…However, we cannot exclude the possibility that this theory might be applicable for HPV16 in the future. Additional factors should be taken into consideration in order to lead to more accurate conclusions about cervical cancer risk, such as multiple HR-HPV infections, viral DNA integration, the methylation status of HPV DNA and mutations into the host target proteins ( Refs 13,18,34,[158][159][160].…”

Section: Discussionmentioning

confidence: 99%

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

Bletsa¹,

Zagouri

Amoutzias

et al. 2021

Expert Rev. Mol. Med.

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Human papillomavirus 16 (HPV16) infection is the aetiologic factor for the development of cervical dysplasia and is regarded as highly carcinogen, because it is implicated in more than 50% of cervical cancer cases, worldwide. The tumourigenic potential of HPV16 has triggered the extensive sequence analysis of viral genome in order to identify nucleotide variations and amino acid substitutions that influence viral oncogenicity and subsequently the initiation and progression of cervical cancer. Nowadays, specific mutations of HPV16 DNA have been associated with an increased risk of high-grade squamous intraepithelial lesions and invasive cervical cancer (ICC) development, including E6 : Q14H, H78Y, L83V, Ε7 : N29S, S63F, E2 : H35Q, P219S, T310K, E5 : I65V, whereas highly conserved regions of viral DNA have been extensively characterised. In addition, numerous novel HPV16 mutations are observed among the studied populations from various geographic regions, hence advocating that different HPV16 strains seem to emerge with different tumourigenic capacities. The present review focuses on the variability of the early genes and the long control region, emphasising on the association of specific mutations with the development of severe dysplasia. Finally, it evaluates whether specific regions of HPV16 DNA are able to serve as valuable biomarkers for cervical cancer risk.

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Section: Discussionmentioning

confidence: 99%

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

Bletsa¹,

Zagouri

Amoutzias

et al. 2021

Expert Rev. Mol. Med.

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“…To date, over 30 genes have been studied for their role in cervical cancer risk and these include, Bid, BRIP1, Caspase 8, CCR2, CTLA4, CYP1A1, EXO1, FASLG, FASR, HOTAIR, IFN gamma, PARP1, XRCC1, MDM2, IL10, IL12, HLA B/C, MTHFR, Tap2, TNF-a, TLR9, p16, PIK3CA, p21, and p53 Martínez-Nava et al, 2016;Mehta et al, 2015;Mei et al, 2014;Dos Santos et al, 2016;Sousa et al, 2011;Tsakogiannis et al, 2017;and Wang et al, 2017). Of these, genes only nine have been researched in African populations, highlighting a big gap in cervical cancer molecular epidemiology studies in a continent where 90% of the cervical cancer-related deaths are predicted (MboubaBouassa et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Current reports show the involvement of Caspase 8, CCR2, CTLA4, CYP1A1, EXO1, FASLG, FASR, HOTAIR, IFN gamma, PARP1, XRCC1, MDM2, IL10, IL12, HLA B/C, MTHFR, Tap2, TNF-a, TLR9, p16, PIK3CA, and p21 in cervical susceptibility (Alanazi et al, 2013;Barbisan et al, 2012;Chang et al, 2015;Jin et al, 2017;Ma et al, 2013;Martínez-Nava et al, 2016;Mehta et al, 2015;Mei et al, 2014;Piccolo and Crispi, 2012;Roszack et al, 2014;Dos Santos et al, 2016;Sousa et al, 2011;Tsakogiannis et al, 2017;Wang et al, 2017;and Zhuo et al, 2014). However, these findings have mostly been corroborated in Caucasian and Asian populations, and only a few have been reported on African populations.…”

Section: Genetics and Cervical Cancermentioning

confidence: 99%

Genetic Susceptibility for Cervical Cancer in African Populations: What Are the Host Genetic Drivers?

Kuguyo

Tsikai

Thomford

et al. 2018

OMICS: A Journal of Integrative Biology

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Human papillomavirus (HPV) is an essential but not a sufficient cervical cancer etiological factor. Cancer promoters, such as host genetic mutations, significantly modulate therapeutic responses and susceptibility. In cervical cancer, of interest have been viral clearing genes and HPV oncoprotein targets, for which conflicting data have been reported among different populations. This expert analysis evaluates cervical cancer genetic susceptibility biomarkers studied in African populations. Notably, the past decade has seen Africa as a hotbed of biomarker and precision medicine innovations, thus potentially informing worldwide biomarker development strategies. We conducted a critical literature search in PubMed/MEDLINE, Google Scholar, and Scopus databases for case-control studies reporting on cervical cancer genetic polymorphisms among Africans. We found that seven African countries conducted cervical cancer molecular epidemiology studies in one of Casp8, p53, CCR2, FASL, HLA, IL10, TGF-beta, and TNF-alpha genes. This analysis reveals a remarkable gap in cervical cancer molecular epidemiology among Africans, whereas cervical cancer continues to disproportionately have an impact on African populations. Genome-wide association, whole exome-and whole-genome sequencing studies confirmed the contribution of candidate genes in cervical cancer. With such advances and omics technologies, the role of genetic susceptibility biomarkers can be exploited to develop novel interventions to improve current screening, diagnostic and prognostic methods worldwide. Exploring these genetic variations is crucial because African populations are genetically diverse and some variants or their combined effects are yet to be discovered and translated into tangible clinical applications. Thus, translational medicine and flourishing system sciences in Africa warrant further emphasis in the coming decade.

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“…Thus, even though p16 represents an excellent biomarker, such observations should be considered as limitations of this marker. Interestingly, specific SNPs in p16 have been recently associated with either protection or risk to cervical cancer lesions, which further increases p16 value in screening HSIL [128,129].…”

Section: P16 Ink4amentioning

confidence: 99%

Cervical cancer risk profiling: molecular biomarkers predicting the outcome of hrHPV infection

Molina

Diatricch

Quintana

et al. 2020

Expert Review of Molecular Diagnostics

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Introduction: Cervical cancer affects half a million women worldwide annually. Given the association between high-risk human papillomavirus (hrHPV) infection and carcinogenesis, hrHPV DNA testing became an essential diagnostic tool. However, hrHPV alone does not cause the disease, and, most importantly, many cervical lesions regress to normal in a year because of the host immune system. Hence, the low specificity of hrHPV DNA tests and their inability to predict the outcome of infections have triggered a further search for biomarkers. Areas covered: We evaluated the latest viral and cellular biomarkers validated for clinical use as primary screening or triage for cervical cancer and assessed their promise for prevention as well as potential use in the future. The literature search focused on effective biomarkers for different stages of the disease, aiming to determine their significance in predicting the outcome of hrHPV infections. Expert opinion: Biomarkers such as p16/Ki-67, hrHPV genotyping, hrHPV transcriptional status, and methylation patterns have demonstrated promising results. Their eventual implementation in the screening programs may support the prompt diagnosis of hrHPV infection and its progression to cancer. These biomarkers will help in making clinical management decisions on time, thus, saving the lives of hrHPV-infected women, particularly in developing countries.

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Association of p16 (CDKN2A) polymorphisms with the development of HPV16‐related precancerous lesions and cervical cancer in the Greek population

Cited by 11 publications

References 37 publications

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

Genetic variability of the HPV16 early genes and LCR. Present and future perspectives

Genetic Susceptibility for Cervical Cancer in African Populations: What Are the Host Genetic Drivers?

Cervical cancer risk profiling: molecular biomarkers predicting the outcome of hrHPV infection

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