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

2021 ◽  
Vol 23 ◽  
Author(s):  
G. Bletsa ◽  
F. Zagouri ◽  
G. D. Amoutzias ◽  
M. Nikolaidis ◽  
E. Zografos ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Cervical Dysplasia ◽  
Long Control Region ◽  
Severe Dysplasia ◽  
Human Papillomavirus 16 ◽  
Early Genes ◽  
Cervical Cancer Risk ◽  
Increased Risk ◽  
Intraepithelial Lesions

Abstract 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.

scholarly journals Dietary factors and in situ and invasive cervical cancer risk in the European prospective investigation into cancer and nutrition study

2010 ◽  
Vol 129 (2) ◽  
pp. 449-459 ◽  
Author(s):  
Carlos A. González ◽  
Noemie Travier ◽  
Leila Luján-Barroso ◽  
Xavier Castellsagué ◽  
F. Xavier Bosch ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Risk ◽  
Invasive Cervical Cancer ◽  
Dietary Factors ◽  
Cervical Cancer Risk ◽  
Nutrition Study ◽  
Prospective Investigation

Human papillomavirus, coinfection with Schistosoma hematobium, and cervical neoplasia in rural Tanzania

2003 ◽  
Vol 13 (4) ◽  
pp. 505-509 ◽  
Author(s):  
K. U. Petry ◽  
U. Scholz ◽  
B. Hollwitz ◽  
R. Von Wasielewski ◽  
C. J.L.M. Meijer
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Invasive Cervical Cancer ◽  
Clinical History ◽  
Hpv Infection ◽  
Separate Analysis ◽  
Hpv Dna ◽  
Rural Tanzania ◽  
Increased Risk ◽  
Local Immunosuppression

Cervical cancer is the most common malignant tumor among women in Tanzania and other countries in tropical Africa. Genital schistosomiasis has been proposed as a possible cofactor in the genesis of this malignant disease that might contribute to its high incidence in regions where bilharzias is endemic. One hundred nine Tanzanian patients from an area with endemic bilharzias who were transferred to a gynecologic out-patient clinic were age-matched with 109 German controls. In patients and controls, separate samples were taken for cytologic assessment and human papillomavirus (HPV) DNA detection using the Hybrid Capture 2 assay (HC2) and PCR (GP5+/6 +). Samples that tested positive for HPV DNA with general primers were re-tested with HPV type-specific primers. After application of 3% acetic acid, punch biopsies were taken from any cervical lesion. Patients were interviewed for recent symptoms or clinical history suggestive of bilharzias. Urine samples from all patients were examined for the presence of schistosoma hematobium ova. Additionally six Tanzanian patients with invasive cervical cancer were included for separate analysis. Patients and controls had an identical prevalence of HPV-DNA (21.5%) using HC2. Based on PCR results with general primers, the corresponding prevalence was 34.5% for Tanzanian cases and 26.9% for German controls. A history suggestive of bilharzias and/or active schistosomiasis were associated with a significantly increased risk for infection with high-risk HPV types. We conclude that infection with Schistosoma hematobium seems to favor persistent genital HPV infection either by traumatizing the genital epithelium and/or by local immunosuppression.

scholarly journals Dietary Inflammatory Index and Its Relationship with Cervical Carcinogenesis Risk in Korean Women: A Case-Control Study

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1108 ◽  
Author(s):  
Sundara Raj Sreeja ◽  
Hyun Yi Lee ◽  
Minji Kwon ◽  
Nitin Shivappa ◽  
James R. Hebert ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Risk ◽  
Multinomial Logistic Regression ◽  
Gynecologic Oncology ◽  
Cervical Carcinogenesis ◽  
Korean Women ◽  
Dietary Inflammatory Index ◽  
Inflammatory Index ◽  
Cervical Cancer Risk ◽  
Increased Risk

Several studies have reported that diet’s inflammatory potential is related to chronic diseases such as cancer, but its relationship with cervical cancer risk has not been studied yet. The aim of this study was to investigate the association between Dietary Inflammatory Index (DII®) and cervical cancer risk among Korean women. This study consisted of 764 cases with cervical intraepithelial neoplasia (CIN)1, 2, 3, or cervical cancer, and 729 controls from six gynecologic oncology clinics in South Korea. The DII was computed using a validated semiquantitative Food Frequency Questionnaire (FFQ). Odds ratios and 95% CI were calculated using multinomial logistic regression. Higher DII scores were associated with higher cervical carcinogenesis risk. A significant association was observed between the DII and risk among CIN2/3 [Odds Ratio (OR) = 3.14; 95% Confidence Intervals (CI) = 1.57–6.29] and cervical cancer patients (OR = 1.98; 95% CI = 1.01–3.88). Among Human Papilloma Virus (HPV)-positive women, a significant association was found between DII and cervical carcinoma risk with CIN2/3 (OR = 5.65; 95% CI = 1.38–23.2). Moreover, women with CIN2/3 and cervical cancer showed a significant association with proinflammatory diet in people without of physical activity (OR = 3.79; 95% CI = 1.81–7.93). These findings suggest that high intake of proinflammatory diets is associated with increased risk of cervical carcinogenesis among women with CIN2/3. Further evaluation in future studies to confirm this association is warranted.

scholarly journals Association between HLA-DP Gene Polymorphisms and Cervical Cancer Risk: A Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Lin Cheng ◽  
Yan Guo ◽  
Shipeng Zhan ◽  
Peiyuan Xia
Keyword(s):  
Cervical Cancer ◽  
Cancer Risk ◽  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Human Leukocyte ◽  
Cervical Cancer Risk ◽  
Leukocyte Antigens ◽  
Knowledge Infrastructure ◽  
Increased Risk ◽  
The Relationship

Objective. We aimed to derive a more precise estimation of the associations between human leukocyte antigens DP (HLA-DP) gene polymorphisms and cervical cancer risk by meta-analysis. Methods. PubMed, EMBASE, ScienceDirect, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were systematically searched to identify studies investigating the relationship between HLA-DP gene polymorphisms and cervical cancer. The associations between them were evaluated by pooled OR and 95% CI. Results. A total of 11 studies including 5008 cases and 9322 controls with 11 HLA-DP alleles were included in the current meta-analysis. Results. The results showed that HLA-DPB1⁎03:01 was significantly associated with an increased risk of cervical cancer (OR=1.252, 95%CI: 1.116-1.403, Pz=0.001), while HLA-DPB1⁎04:02 and HLA-DP rs3117027 G allele were significantly associated with a decreased risk of cervical cancer (OR=0.744, 95%CI: 0.652-0.848, Pz=0.001; OR=0.790, 95%CI: 0.745-0.837, Pz=0.001), and HLA-DP rs9277535 G allele was significantly associated with a decreased risk of cervical cancer in Asia (OR=0.802, 95%CI: 0.753-0.855, Pz=0.001). Subgroup analyses based on race system showed that HLA-DPB1⁎13:01 was significantly associated with an increased risk of cervical cancer in Asia (OR=1.834, 95%CI: 1.107-3.039, Pz=0.019). No significant association was established for the HLA-DP following alleles: DPB1⁎02:01, DPB1⁎02:02, DPB1⁎04:01, DPB1⁎05:01, rs4282438, and rs3077. Conclusion. HLA-DP gene polymorphisms (HLA-DPB1⁎03:01, DPB1⁎04:02, DPB1⁎13:01, rs9277535, and rs3117027) were significantly associated with cervical cancer.

scholarly journals Clinical Features of Women Diagnosed With Invasive Cervical Cancer in Ghana

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 40s-40s
Author(s):  
Y. Nartey ◽  
P. Hill ◽  
K. Amo-Antwi ◽  
K. Nyarko ◽  
J. Yarney ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Clinical Features ◽  
Teaching Hospital ◽  
Cervical Screening ◽  
Invasive Cervical Cancer ◽  
Figo Stage ◽  
Middle Income ◽  
Increased Risk ◽  
Referral Hospitals

Background: The incidence of cervical cancer continues to increase in many low- and middle-income countries. It remains the commonest cancer affecting females in Ghana. However, comprehensive information on the clinical characteristics of women diagnosed with invasive cervical cancer is scarce. Aim: To characterize the clinical features of women with invasive cervical cancer in Ghana. Methods: We conducted a retrospective study in two large referral hospitals in Ghana: the Korle Bu teaching hospital, Accra and Komfo Anokye teaching hospital, Kumasi. Through the review of paper-based, electronic, and pathology medical records, information on women diagnosed with invasive cervical cancer from 1st January 2010 to 31st December 2013 was collected. The information was entered onto a standardized data abstraction sheet and included demographics, comorbid conditions, treatment and follow-up. All analyses were conducted in STATA and described the distribution of key clinical features by the stage at diagnosis. Results: A total of 1,725 women with invasive cervical cancer were included in the analysis. Few had cervical screening before their cervical cancer diagnosis (1.1%). Women who were resident in a metropolitan area ( P = 0.034), or who had any comorbidity ( P < 0.001) were at an increased risk of FIGO stage III-IV disease. The majority of women had at least two diagnostic investigations (75%) with cervical biopsy performed for 95.5% of women. More than half received radiotherapy (55.4%) and only 22.4% receiving chemotherapy. Clinical follow-up after the first consultation was performed for 61%, with 73% of women with clinical follow-up having at least one follow-up investigation. Conclusion: Improvements in access to early diagnosis and optimal treatment of cervical cancer, such as an increased use of chemoradiation would reduce the burden of the disease in Ghana.

scholarly journals Genetic polymorphisms of PGF and TNFAIP2 genes related to cervical cancer risk among Uygur females from China

2020 ◽  
Author(s):  
Zumurelaiti Ainiwaer ◽  
Reyilanmu Maisaidi ◽  
Jing Liu ◽  
Lili Han ◽  
Sulaiya Husaiyin ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Case Control Study ◽  
Case Control ◽  
Positive Interaction ◽  
Female Population ◽  
Cervical Cancer Risk ◽  
Increased Risk ◽  
Relationship Of ◽  
The Relationship ◽  
Control Study

Abstract Background: PGF and TNFAIP2 are important angiogenic factors, which were abnormal expression in cervical cancer (CC). However, there is currently no report investigating the relationship of PGF and TNFAIP2 gene polymorphisms to CC risk.Methods: We conducted a case-control study of 342 CC patients and 498 cancer-free controls in a Chinese Uygur female population. Three SNPs (PGF rs8019391, PGF rs2268615, and TNFAIP2 rs710100) were selected and genotyped to assess the possible association of PGF and TNFAIP2 polymorphisms with CC susceptibility. Logistic regression analysis adjusted by age was used.Results: PGF rs2268615 (OR = 1.39, 95% CI = 1.04-1.86, p = 0.024) and TNFAIP2 rs710100 (OR = 1.44, 95% CI =1.07-1.95, p = 0.018) polymorphisms were associated with the increased risk of CC. Moreover, T allele of PGF rs8019391 was highly represented in patients with stage III–IV compared with stage I-II (OR = 2.17, p = 4.58´10-4). MDR analysis revealed a positive interaction between the SNPs.Conclusion: Our data indicated that PGF rs2268615, and TNFAIP2 rs710100 polymorphisms might be risk factors for CC susceptibility, which contributed to the increased risk of CC.Trail registration: Not applicable.

scholarly journals Genetic Polymorphisms of PGF and TNFAIP2 Genes Related to Cervical Cancer Risk Among Uygur Females from China

2020 ◽  
Author(s):  
Zumurelaiti Ainiwaer ◽  
Reyilanmu Maisaidi ◽  
Jing Liu ◽  
Lili Han ◽  
Sulaiya Husaiyin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cervical Cancer ◽  
Case Control Study ◽  
Tumor Stage ◽  
Case Control ◽  
Positive Interaction ◽  
Female Population ◽  
Cervical Cancer Risk ◽  
Increased Risk ◽  
Control Study

Abstract Background: PGF and TNFAIP2 are important angiogenic factors, which were abnormal expression in cervical cancer (CC). However, no report was investigating the associations between the polymorphisms in the PGF and TNFAIP2 genes and CC risk. Methods: We conducted a case-control study of 342 CC patients and 498 cancer-free controls in Chinese Uygur female population. Three selected SNPs (PGF rs8019391, PGF rs2268615, and TNFAIP2 rs710100) were genotyped to investigate the possible association of the polymorphisms in PGF and TNFAIP2 with the risk of CC. The analysis adjusted by age was used to assess associations of these SNPs with CC risk. Results: PGF rs2268615 (OR = 1.39, 95% CI = 1.04-1.86, p = 0.024) and TNFAIP2 rs710100 (OR = 1.44, 95% CI =1.07-1.95, p = 0.018) polymorphisms were significantly associated with the increased risk of CC. Moreover, PGF rs8019391 T allele was highly represented in patients with III–IV tumor stage (OR = 2.17, p = 4.58´10-4). MDR analysis revealed a positive interaction between the SNPs. Conclusion: Our data suggested that PGF rs2268615, and TNFAIP2 rs710100 polymorphisms may be risk factors for susceptibility to CC, which contributed to the increased risk of CC, and this finding requires further validation by larger studies.Trail registration: Not applicable.

scholarly journals High Levels of Within-Host Variations of Human Papillomavirus 16 E1/E2 Genes in Invasive Cervical Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Yusuke Hirose ◽  
Mayuko Yamaguchi-Naka ◽  
Mamiko Onuki ◽  
Yuri Tenjimbayashi ◽  
Nobutaka Tasaka ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Viral Replication ◽  
Viral Genome ◽  
Invasive Cervical Cancer ◽  
Infected Woman ◽  
Human Papillomavirus 16 ◽  
Normal Cervix ◽  
High Level

Human papillomavirus type 16 (HPV16) is the most common HPV genotype found in invasive cervical cancer (ICC). Recent comprehensive genomics studies of HPV16 have revealed that a large number of minor nucleotide variations in the viral genome are present in each infected woman; however, it remains unclear whether such within-host variations of HPV16 are linked to cervical carcinogenesis. Here, by employing next-generation sequencing approaches, we explored the mutational profiles of the HPV16 genome within individual clinical specimens from ICC (n = 31) and normal cervix (n = 21) in greater detail. A total of 367 minor nucleotide variations (167 from ICC and 200 from the normal cervix) were detected throughout the viral genome in both groups, while nucleotide variations at high frequencies (&gt;10% abundance in relative read counts in a single sample) were more prevalent in ICC (10 in ICC versus 1 in normal). Among the high-level variations found in ICC, six were located in the E1/E2 genes, and all of them were non-synonymous substitutions (Q142K, M207I, and L262V for E1; D153Y, R302T, and T357A for E2). In vitro functional analyses of these E1/E2 variants revealed that E1/M207I, E2/D153Y, and E2/R302T had reduced abilities to support viral replication, and that E2/D153Y and E2/R302T failed to suppress the viral early promoter. These results imply that some within-host variations of E1/E2 present at high levels in ICC may be positively selected for and contribute to cervical cancer development through dysfunction or de-stabilization of viral replication/transcription proteins.

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