Comprehensive mapping of the human papillomavirus (HPV) DNA integration sites in cervical carcinomas by HPV capture technology

The clinical implications of specific human papillomavirus (HPV) types in invasive cervical carcinomas are only now beginning to be appreciated. The objective of this study was to determine the clinical implications and prognostic value of the HPV genotype in cervical carcinomas. In this study, we employed an HPV DNA chip to detect the type-specific sequence of HPV from cervical swabs taken from women with biopsy-proven neoplastic lesions of the cervix. We divided the patients into four groups: HPV-negative, HPV-16-related, HPV-18-related, and intermediate risk type–related. Associations with clinicopathologic data (stage, histologic type, lymph node status, parametrial invasion, lymphvascular space invasion, tumor size, vaginal involvement) and overall survival were assessed. HPV DNA was detected in 81.4% of the patients, and 19.0% harbored multiple HPV variants. HPV-16-related was the predominant type and was detected in 47.4% (46/97) of the patients. The HPV-16-related types were detected more frequently in patients with squamous cell carcinomas, whereas the HPV-18-related types were more prevalent in cases of adenocarcinomas and adenosquamous carcinomas (P< 0.05). Otherwise, no significant correlations were detected between the HPV genotype and any other clinicopathologic parameters. After a median follow-up of 30 months, the 5-year survival rate was lower in the HPV-18-related patients, but this difference was not found to be statistically significant, according to the results of the log-rank test. We conclude that neither the presence nor type of HPV DNA bears any prognostic significance in cases of cervical carcinoma.

Download Full-text

A prospective study of the relationship between prediagnostic Human Papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas

British Journal of Cancer ◽

10.1038/sj.bjc.6600454 ◽

2002 ◽

Vol 87 (2) ◽

pp. 175-180 ◽

Cited By ~ 23

Author(s):

E Sigstad ◽

A K Lie ◽

T Luostarinen ◽

J Dillner ◽

E Jellum ◽

...

Keyword(s):

Human Papillomavirus ◽

Prospective Study ◽

Hpv Dna ◽

Cervical Carcinomas ◽

A Prospective Study ◽

The Relationship

Download Full-text

Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions

International Journal of Molecular Sciences ◽

10.3390/ijms22063242 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3242

Author(s):

María Lourdes Garza-Rodríguez ◽

Mariel Araceli Oyervides-Muñoz ◽

Antonio Alí Pérez-Maya ◽

Celia Nohemí Sánchez-Domínguez ◽

Anais Berlanga-Garza ◽

...

Keyword(s):

Direct Evidence ◽

Clonal Selection ◽

Early Stage ◽

Cervical Lesions ◽

Dna Integration ◽

Hpv Dna ◽

Genome Integration ◽

Integration Sites ◽

Hpv Types ◽

Cancer Studies

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.

Download Full-text

Simultaneous mapping of human papillomavirus integration sites and molecular karyotyping in short-term cultures of cervical carcinomas by using 49-color combined binary ratio labeling fluorescence in situ hybridization

Cancer Genetics and Cytogenetics ◽

10.1016/s0165-4608(01)00620-3 ◽

2002 ◽

Vol 134 (2) ◽

pp. 145-150 ◽

Cited By ~ 18

Author(s):

Antoinette A.T.P Brink ◽

Joop C.A.G Wiegant ◽

Károly Szuhai ◽

Hans J Tanke ◽

Gemma G Kenter ◽

...

Keyword(s):

In Situ Hybridization ◽

Human Papillomavirus ◽

Fluorescence In Situ Hybridization ◽

Molecular Karyotyping ◽

Short Term ◽

Cervical Carcinomas ◽

Integration Sites

Download Full-text

HPV-DNA-Integration in Oropharynxkarzinomen

Laryngo-Rhino-Otologie ◽

10.1055/s-2004-823549 ◽

2004 ◽

Vol 83 (02) ◽

Author(s):

JP Klussmann ◽

S Dinh ◽

C Wittekindt ◽

L Turek ◽

E Smith ◽

...

Keyword(s):

Dna Integration ◽

Hpv Dna

Download Full-text

Comparison of Human Papillomavirus (HPV) detection in urine and cervical samples using high-risk HPV DNA testing in Northern Thailand

10.26226/morressier.578f37fad462b8028d88f8f5 ◽

2016 ◽

Author(s):

Surapan Khunamornpong

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Dna Testing ◽

Northern Thailand ◽

Hpv Dna ◽

Hpv Dna Testing ◽

High Risk Hpv

Download Full-text

Prevalence and genotype distribution of human papillomavirus in Czech non-vaccinated heterosexual couples

Virology Journal ◽

10.1186/s12985-021-01551-x ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Hana Jaworek ◽

Vladimira Koudelakova ◽

Ivana Oborna ◽

Blazena Zborilova ◽

Jana Brezinova ◽

...

Keyword(s):

Human Papillomavirus ◽

Hpv Infection ◽

Sexual Partners ◽

Fisher Exact Test ◽

Genotype Distribution ◽

Heterosexual Couples ◽

Anatomic Site ◽

Hpv Dna ◽

Hpv Test ◽

Penile Swabs

Abstract Background Data about the genotype-specific human papillomavirus (HPV) prevalence in the Czech Republic is limited. We aimed to evaluate the prevalence and concordance of genotype-specific HPV infection detected in semen samples, penile swabs and cervical swabs from non-vaccinated heterosexual couples without HPV-associated disease. Methods Semen samples and penile swabs were collected from male partners and cervical swabs were collected from female partners of heterosexual couples treated for infertility (n = 195). Presence of HPV DNA in semen samples and cervical swabs was analyzed using the cobas® HPV Test and PapilloCheck®. Only the PapilloCheck® test was used to detect HPV in penile swabs. The genotype-specific prevalence and concordance of HPV infection not targeted by vaccine were evaluated using Fisher exact test. Results Both partners were infected with any HPV type in 13.8% (27/195) of couples and, of these couples, 55.6% (15/27) harbored at least one mutual genotype. High-risk HPV (hrHPV) genotypes were detected in 12.3% (24/195) of semen samples, 31.3% (61/195) of penile swabs, and 19.5% (38/195) of cervical swabs (P < 0.001). The most prevalent hrHPV genotype were HPV53 (2.56%; 5/195) in semen samples, HPV16 (6.67%, 13/195) in penile swabs and HPV39 (3.59%, 7/195) in cervical swabs. Low-risk (lrHPV) genotypes were detected in 5.13% (10/195) of semen samples, 15.9% (31/195) of penile swabs, and 4.10% (8/195) of cervical swabs (P < 0.001). Male sexual partners of HPV-positive women were more likely to be infected with at least one of the same HPV types than female sexual partners of HPV-positive men (34.9% vs. 17.9%, P = 0.055). Conclusions This study showed that the detection of HPV infection differ by anatomic site and gender. Regardless the anatomic site, high prevalence of HPV genital infection was found in both Czech men and women.

Download Full-text

Triage of human papillomavirus infected women by methylation analysis in first-void urine

Scientific Reports ◽

10.1038/s41598-021-87329-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Severien Van Keer ◽

Annina P. van Splunter ◽

Jade Pattyn ◽

Annemie De Smet ◽

Sereina A. Herzog ◽

...

Keyword(s):

Human Papillomavirus ◽

Host Cell ◽

Intraepithelial Neoplasia ◽

Underlying Disease ◽

Hpv Infection ◽

Molecular Testing ◽

High Grade ◽

Methylation Analysis ◽

Hpv Dna ◽

Screening Attendance

AbstractHost cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59–0.92) and 0.76 (95% CI 0.58–0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.

Download Full-text