Genome-wide association analysis in host genetic characteristics of progression to high-grade cervical intraepithelial neoplasia or higher for women with human papillomavirus infection and normal cytology.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6033-6033
Author(s):  
Chyong-Huey Lai ◽  
Su-Wei Chang ◽  
Lan-Yan Yang ◽  
Shuen-Iu Hung ◽  
Chiao-Yun Lin ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Roc Curve ◽  
Intraepithelial Neoplasia ◽  
Genome Wide Association ◽  
Normal Cytology ◽  
Genetic Characteristics ◽  
Risk Alleles ◽  
Genome Wide

6033 Background: Human papillomavirus (HPV) testing is widely used for cervical cancer screening. The hazard ratio of developing cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in HPV-positive/ normal cytology women is 20–34 fold as compared to those with HPV-negative/normal cytology. HPV-positivity would cause substantial anxiety. Apart from viral factors such as high-risk (hr) types, it is important to identify host characteristics for predicting outcome. Methods: An initial genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) by Affymetrix Axiom™ Genome-Wide Human Arrays was conducted on 505 cases with histological diagnosis of CIN2+ (group D1) versus 920 female controls. An additional set of 2315 female controls from the Taiwan Biobank genotype array were added in the discovery stage. The identified 29 CIN2+ -associated SNPs from GWAS (p < 5 x 10−6) were verified in an independent cohort (group D2 [n = 306] versus group N [n = 600]). Group N were HPV-negative/normal cytology women from a population-based cervical cytology and HPV co-test study. A cohort with HPV-positive/normal cytology (group P, n = 755) underwent follow-up and was served as the prediction set. The predictive validity was analyzed by logistic regression and receiver operating characteristic (ROC) curve analysis. Results: Thirty-three individuals of the group P progressed to CIN2+ (median follow-up: 23.7 months, range 4.0–122.1). A risk-predictive panel of 8 SNPs rs3097662, rs35979982, rs7763822, rs4282438, rs3128927, rs7759943, rs213194, rs17835649 which were significant in the replication (p < 0.05) was used to train models for disease risk prediction using the combination of GWAS and verification sets. Two prediction models were finalized and determined using 7 SNPs for hr- and low-risk (lr) HPV groups respectively (sensitivity 0.72 and 0.75, specificity 0.651 and 0.884, area under the ROC curve 0.703 and 0.701). Among group P with hr-HPV, those carried < 6 risk-alleles had significantly decreased hazard (log-rank p < 0·001) of progression to CIN2+ than those with ≧6 risk-alleles, while among group P with lr-HPV, those with predictive probability of ≥ 0·095 had a cumulative risk of progression of 10% at 3 years. Conclusions: Two risk-predictive SNP panels including 7 SNPs with hr- or lr-HPV groups can assist risk stratification among HPV-positive/ normal cytology women. These panels could be further tested in other ethnic populations.

Genome-wide association analysis in host characteristics of progression to high-grade cervical intraepithelial neoplasia for women with human papilloma virus infection and normal cytology.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5109-5109
Author(s):  
Chyong-Huey Lai ◽  
Angel Chao ◽  
Chiao-Yun Lin ◽  
Chu-Chun Huang ◽  
Wen-Hui Su
Keyword(s):  
Cervical Intraepithelial Neoplasia ◽  
Membrane Trafficking ◽  
Intraepithelial Neoplasia ◽  
Genome Wide Association ◽  
Chromosome 17 ◽  
Normal Cytology ◽  
Genetic Characteristics ◽  
Genome Wide ◽  
A Genome

5109 Background: Although it is well accepted that persistent human papillomavirus (HPV) is necessary for carcinogenesis of cervical neoplasms, the molecular mechanism for progression is unclear. HPV testing is widely used for cervical cancer screening. The hazard ratio of developing cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) in baseline HPV-positive/normal cytology women is 30-50 fold as compared with HPV-negative/normal cytoloy women. HPV positivity would cause substantial anxiety. It is important to identify a prognostic profile for predicting progression. Methods: We collected blood samples from women aged ≥ 30 years in a population-based nested cohort study enrolling women with HPV infection (n = 871) or HPV-negative (n = 902) with normal cytology in 2004-2009 for prospective follow-up. To identify the host genetic characteristics associated with cervical carcinogenesis, a genome-wide association study (analyzing 530,194 SNPs) was conducted in 23 cases who developed CIN2+ and 62 viral type- and age-matched controls who were HPV-positive at baseline without developing CIN throughout the follow-up period. Results: One SNP with significant P values (rs16969682; P=4.58 x 10-5, OR=5.9, 95% CI=2.52-13.96) located in SEC14-like 1 (SEC14L1) gene localized to chromosome 17 was identified with association between progression to CIN2+ and controls without CIN throughout follow-up. SEC14L1 belongs to the widely-expressed SEC14-superfamily. This superfamily consists of > 500 members that are involved in biological functions including membrane trafficking and phospolipid metabolism. Furthermore, using T-cell based cDNA screening, SEC14L-1a is identified as a regulator of HIV-1 replication. Conclusions: The potential role of SEC14L1 in host-viral interaction will be further elucidated. Additional statistically significant SNPs including rs16969682 will be validated on cases with CIN2+ (n = 250) and normal controls (normal cytology/HPV-negative at baseline without acquisition of HPV or abnormal cytology/histology during follow-up, n = 500).

Monitoring of patients with cervical intraepithelial neoplasia after excisional treatment

2021 ◽  
Vol 20 (1) ◽  
pp. 113-120
Author(s):  
N.V. Zarochentseva ◽  
◽  
L.K. Dzhidzhikhiya ◽  
V.N. Nabieva ◽  
◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
World Literature ◽  
Intraepithelial Neoplasia ◽  
Routine Screening ◽  
Diagnostic Methods ◽  
Almost Everywhere ◽  
Combined Test ◽  
Operative Monitoring

Cervical intraepithelial neoplasia (CIN) refers to precancerous changes in the cervix. After surgical treatment, a certain proportion of patients remain at risk of disease reccurence. Therefore, monitoring of patients after CIN surgery is an important and necessary part of their management tactics. Objective. Review of world literature on modern approaches to patients monitoring after using excisional methods of CIN treatment. Materials and methods. The information material includes data from scientific articles on the subject available in Pubmed and published over the past 20 years. Results. The analysis of data contained in modern literature on the frequency and risk factors for the development of reccurent CIN after excisional methods of treatment, diagnostic methods, the timing of follow-up examinations during post-operative monitoring, the main approaches to monitoring in different countries and the effectiveness of the proposed strategies for postoperative follow-up of patients after treatment was conducted. It was established that the approaches to the observation of this category of patients differ in various countries. Almost everywhere, the priority tool for monitoring of patients with CIN after treatment is a combined test, which involves a joint use of cytology and human papillomavirus tests. The main difference between countries is the timing of the first post-treatment follow-up visit. In some countries a follow-up visit is recommended within 24 months, while in others it is suggested to return to routine screening if the primary combined test is negative. Conclusion. Despite existing disagreements, the proposed post-operative monitoring strategies for CIN patients provide a fairly high percentage of “healing” and return to routine screening. Key words: human papillomavirus, monitoring, cervical cancer, cervical intraepithelial neoplasia, excisional treatment

scholarly journals Ten-year follow-up of human papillomavirus vaccine efficacy against the most stringent cervical neoplasia end-point—registry-based follow-up ofthree cohorts from randomized trials

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e015867 ◽  
Author(s):  
Matti Lehtinen ◽  
Camilla Lagheden ◽  
Tapio Luostarinen ◽  
Tiina Eriksson ◽  
Dan Apter ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Registry ◽  
Vaccine Efficacy ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Hpv 16 ◽  
Link Type

ObjectiveDue to long lag time between infection/cancer diagnoses human papillomavirus (HPV) vaccination programs will deliver vaccine efficacy (VE) estimates against cancer end-points late. Cancer registry follow-up of population-based, randomised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer (CIN3+).MethodsWe report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and/or cluster randomised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005, and between May 2004 and April 2005, respectively. The cohorts comprised 15 627 18- to 19-year-old unvaccinated women (NCT01393470), and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA (NCT00122681) and HPV-012 (NCT00169494) trials, respectively. The age-aligned passive follow-up started 6 months after the clinical trials’ end.ResultsDuring the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 (CIN3) and 4 cases of invasive cervical cancer (ICC) in the unvaccinated cohort, and 4 CIN3 cases in the HPV-16/18 vaccinated women. Diagnostic blocks were available for HPV typing from 87% of the cases. CIN3+ lesions were detectable in 54 cases. HPV16 was found in 26 of 50 unvaccinated CIN3+ cases, and in 3 CIN3+ cases in the HPV-16/18 vaccinated women. The latter were all baseline positive for cervical HPV16 DNA. Baseline data was not available for the unvaccinated women. Intention-to-treat VE against any CIN3+ was 66% (95% CI 8, 88).ConclusionsTen years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3+ irrespectively of HPV type. Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects.Trial registration numberNCT01393470.

scholarly journals Genome-Wide Association Study of Prevalent and Persistent Cervical High-Risk Human Papillomavirus(HPV) Infection

2019 ◽  
Author(s):  
Sally N. Adebamowo ◽  
Adebowale A Adeyemo ◽  
Charles N Rotimi ◽  
Olayinka Olaniyan ◽  
Richard B. Offiong ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Principal Component ◽  
Hpv Infection ◽  
Genome Wide Association ◽  
Replication Studies ◽  
Genome Wide

Abstract Background: Genetic factors may influence the susceptibility to high-risk human papillomavirus (hrHPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence. Methods: Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes. Results: The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p=1.43 x 10-6). The top variants associated with cervical hrHPV persistence were in DAP(OR: 6.86, p=7.15 x 10-8), NR5A2(OR: 3.65, p=2.03 x 10-7) and MIR365-2(OR: 7.71, p=2.63 x 10-7) gene regions. Conclusions: This exploratory GWAS yielded novel candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

Follow-up Findings for Women With Human Papillomavirus–Positive and Atypical Squamous Cells of Undetermined Significance Screening Test Results in a Large Women's Hospital Practice

2009 ◽  
Vol 133 (9) ◽  
pp. 1426-1430 ◽  
Author(s):  
Henry Armah ◽  
R. Marshall Austin ◽  
David Dabbs ◽  
Chengquan Zhao
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Test Results ◽  
Clinical Practices ◽  
Squamous Cells ◽  
Hpv Test ◽  
The Impact ◽  
Undetermined Significance

Abstract Context.—Reflex human papillomavirus (HPV) testing has been designated in consensus guidelines as “preferred” for women with atypical squamous cells of undetermined significance (ASC-US) liquid-based cytology (LBC) results, and colposcopy is currently recommended for patients with HPV-positive ASC-US results. Data from large clinical practices using newer screening methods and current cytology terminology are limited. Objectives.—We analyzed data from patients with ASC-US LBC and positive HPV test results. We also assessed the impact of the presence or absence of an endocervical cell/ transformation zone sample (EC/TZS) on biopsy diagnoses. Design.—The information system of a large women's hospital serving an older-than-average population was searched over a 21-month period between July 1, 2005, and March 31, 2007, for HPV-positive cases interpreted as ASC-US (Bethesda System 2001) using computer-imaged LBC. Histologic diagnoses, patient ages, and presence or absence of an EC/TZS were analyzed. The average follow-up period was 7.5 months. Results.—Among 4273 women with HPV-positive ASC-US results, the cumulative cervical intraepithelial neoplasia 2 or 3 (CIN 2/3) and CIN 1 rates for 2192 women with available biopsies were 5.1% and 43.6%, respectively. Cervical intraepithelial neoplasia 2/3 and CIN 1 rates for women with HPV-positive ASC-US results were not significantly different for women with and without an EC/TZS. Conclusions.—The risk of CIN 2/3 in the study population was significantly lower than reported in widely cited trial data. Neither presence nor absence of an EC/TZS, nor the age of the patient, had a statistically significant impact on the likelihood of biopsy diagnoses of CIN 2/3 and CIN 1 for patients with HPV-positive ASC-US test results.

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