Genomic Risk Factors for Cervical Cancer

Ramachandran, Dhanya; Dörk, Thilo

doi:10.3390/cancers13205137

Cited by 28 publications

(20 citation statements)

References 166 publications

(230 reference statements)

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“…Although HPV infection is the critical determinant for the risk of developing CC, not all women infected with HPV develop CC. Host genetic variants and environmental factors also add to the risk towards the susceptibility to CC [176]. Further, the genomic and epigenomic profiling of CC at different stages along with the gene expression analysis supports the role of these events in CC initiation, progression, invasion and metastasis [9,10].…”

Section: Genetic and Epigenetic Features In Cervical Cancer Metastasismentioning

confidence: 71%

“…The most significant loci are 6p21.3 [HLA locus]; 2q13 (PAX8), 5p15.33 (TERT-CLPTM1L), and 17q12 (GSDMB). Polymorphisms in ARRDC3, INS-IGF2, SOX9, TTC34, ACACB have also been associated with a risk of developing CC; however, this remains to be validated [176,178]. Several of these polymorphic genes are potential candidates for immune evasion in distant sites and hence have the ability to promote metastasis.…”

Section: Genetic Predisposition In Cervical Cancermentioning

confidence: 99%

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Multidimensional outlook on the pathophysiology of cervical cancer invasion and metastasis

et al. 2023

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Cervical cancer being one of the primary causes of high mortality rates among women is an area of concern, especially with ineffective treatment strategies. Extensive studies are carried out to understand various aspects of cervical cancer initiation, development and progression; however, invasive cervical squamous cell carcinoma has poor outcomes. Moreover, the advanced stages of cervical cancer may involve lymphatic circulation with a high risk of tumor recurrence at distant metastatic sites. Dysregulation of the cervical microbiome by human papillomavirus (HPV) together with immune response modulation and the occurrence of novel mutations that trigger genomic instability causes malignant transformation at the cervix. In this review, we focus on the major risk factors as well as the functionally altered signaling pathways promoting the transformation of cervical intraepithelial neoplasia into invasive squamous cell carcinoma. We further elucidate genetic and epigenetic variations to highlight the complexity of causal factors of cervical cancer as well as the metastatic potential due to the changes in immune response, epigenetic regulation, DNA repair capacity, and cell cycle progression. Our bioinformatics analysis on metastatic and non-metastatic cervical cancer datasets identified various significantly and differentially expressed genes as well as the downregulation of potential tumor suppressor microRNA miR-28-5p. Thus, a comprehensive understanding of the genomic landscape in invasive and metastatic cervical cancer will help in stratifying the patient groups and designing potential therapeutic strategies.

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Section: Genetic and Epigenetic Features In Cervical Cancer Metastasismentioning

confidence: 71%

Section: Genetic Predisposition In Cervical Cancermentioning

confidence: 99%

Multidimensional outlook on the pathophysiology of cervical cancer invasion and metastasis

et al. 2023

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“…Some of the selected DMPs that constitute the final WID‐HPV are in genes that putatively play a role in the clearance of infected cells following the initial host immune response to the HPV infection (Tables 1 and S2). Altered DNA methylation in the human leukocyte antigen system may affect antigen processing and presentation ( HLA‐DRA gene) and downstream T‐cell mediated apoptosis ( HLA‐A gene), and several variants of the HLA‐locus have been previously linked to cervical cancer susceptibility (reviewed by reference 37). Additionally, altered DNA of the PIAS1 gene may affect sumoylation of the latent cytoplasmic transcription factor STAT1 and in this way modulate the host's innate immune response 38 …”

Section: Resultsmentioning

confidence: 99%

HPV‐induced host epigenetic reprogramming is lost upon progression to high‐grade cervical intraepithelial neoplasia

Herzog

Vavourakis

Barrett

et al. 2023

Intl Journal of Cancer

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The impact of a pathogen on host disease can only be studied in samples covering the entire spectrum of pathogenesis. Persistent oncogenic human papilloma virus (HPV) infection is the most common cause for cervical cancer. Here, we investigate HPV-induced host epigenome-wide changes prior to development of cytological abnormalities. Using cervical sample methylation array data from diseasefree women with or without an oncogenic HPV infection, we develop the WID (Women's cancer risk identification)-HPV, a signature reflective of changes in the healthy host epigenome related to high-risk HPV strains (AUC = 0.78, 95% CI: 0.72-0.85, in nondiseased women). Looking at HPV-associated changes across disease development, HPV-infected women with minor cytological alterations (cervical intraepithelial neoplasia grade 1/2, CIN1/2), but surprisingly not those with precancerous changes or invasive cervical cancer (CIN3+), show an increased WID-HPV index, indicating the WID-HPV may reflect a successful viral clearance response absent in progression to cancer. Further investigation revealed the WID-HPV is positively associated with apoptosis (ρ = 0.48; P < .001) and negatively associated with epigenetic replicative age (ρ = À0.43; P < .001). Taken together, our data suggest the WID-HPV captures a clearance response associated with apoptosis of HPV-infected cells. This response may be dampened or lost with increased underlying replicative age of infected cells, resulting in progression to cancer.

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“…The estimated hereditary incidence of CC oscillates around 7%. Studies in large populations of HPV-negative CC outcomes are needed to verify this data [ 24 , 25 ]. HPV negative CCs are characterized by a variety of clinical courses as well as pathologies.…”

Section: Review Resultsmentioning

confidence: 99%

Cervical Cancer Prophylaxis—State-of-the-Art and Perspectives

Poniewierza¹,

Panek

2022

Healthcare

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Background: Each year 604,127 new cases of cervical cancer (CC) are diagnosed, and 341,831 individuals die from the disease. It is the fourth most common cancer among women and the fourth most common cause of death from female cancers worldwide. The pathogenesis of CC is associated with human papillomavirus (HPV) infections and consists of several steps involving cell proliferation outside the human body’s control mechanisms. Strategies to prevent CC are based on screening and vaccination. Scope of the Review: The aim of this paper was to collect and analyze the available literature on the issue of CC prevention and the impact of the COVID-19 pandemic on its implementation. For this purpose, PubMed and Google Scholar databases were searched using keywords, such as “cervical cancer”; “HPV”; “prevention”; “prophylaxis”; “vaccination”; “screening” and “COVID-19” in different variations. Only articles published since 2018 were included in the study. Conclusions: Selected European countries have different CC prevention programs funded by national budgets. This translates into observed differences in the risk of death from CC (age-standardized rate Malta = 1.1, Poland = 5.9). COVID-19 pandemic due to disruption of CC screening may exacerbate these differences in the future. To improve the situation, new screening methods, such as p16/Ki67, HPV self-testing, and the use of artificial intelligence in colposcopic assessment, should be disseminated, as well as free HPV vaccination programs implemented in all countries. The search for new solutions is not without significance and entails ultra-sensitive screening tests for risk groups (mRNA E6/E7, SOX1/SOX14), HPV vaccines with shorter dosing schedules, and new therapeutic pathways using nanotheranostics.

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Genomic Risk Factors for Cervical Cancer

Cited by 28 publications

References 166 publications

Multidimensional outlook on the pathophysiology of cervical cancer invasion and metastasis

Multidimensional outlook on the pathophysiology of cervical cancer invasion and metastasis

HPV‐induced host epigenetic reprogramming is lost upon progression to high‐grade cervical intraepithelial neoplasia

Cervical Cancer Prophylaxis—State-of-the-Art and Perspectives

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