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Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results.

ABSTRACT: OBJECTIVE:Chromosomal gains at 3q26, 5p15 and 20q13 have been described in cervical precancer and cancer. We evaluated a novel fluorescence in situ hybridization (FISH) assay that detects gains at these three loci simultaneously as a possible biomarker for detecting cervical precancer. METHODS:Chromosomal copy numbers at 3q26, 5p15, 20q13 and the centromere of chromosome7 (cen7) in liquid-based cytology specimens from 168 women enrolled in the Biopsy Study were determined by FISH. The number of cells with ? 3 or ? 4 signals for a genomic locus was enumerated and diagnostic test performance measures were calculated using receiver operating characteristic (ROC) analyses. Sensitivity and specificity values were determined for the detection of CIN2+ and/or HSIL. RESULTS:The median number of cells with ? 3 signals increased with the severity of cervical lesion for each genomic locus (p-trend<0.02 for each locus). ROC analysis for the number of cells with ? 3 signals resulted in area under the curve values of 0.70 (95% CI: 0.54-0.86), 0.67 (0.52-0.83), 0.67 (0.51-0.83) and 0.78 (0.64-0.92) for 3q26, 5p15, 20q13 and cen7, respectively, for the detection of CIN2+ and/or HSIL. Positivity for gains at multiple loci resulted in only slightly better test performance measures than those for the individual probes for four distinct combinations of probes. CONCLUSIONS:Chromosomal gains at 3q26, 5p15, 20q13 and cen7 are associated with severity of cervical lesions. Further studies are required to quantify risk stratification of FISH assays for cervical cancer screening.

SUBMITTER: Luhn P

PROVIDER: S-EPMC3833871 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results.

Luhn Patricia P Houldsworth Jane J Cahill Lynnette L Schiffman Mark M Castle Philip E PE Zuna Rosemary E RE Dunn S Terence ST Gold Michael A MA Walker Joan J Wentzensen Nicolas N

Gynecologic oncology 20130613 3

<h4>Objective</h4>Chromosomal gains at 3q26, 5p15 and 20q13 have been described in cervical precancer and cancer. We evaluated a novel fluorescence in situ hybridization (FISH) assay that detects gains at these three loci simultaneously as a possible biomarker for detecting cervical precancer.<h4>Methods</h4>Chromosomal copy numbers at 3q26, 5p15, 20q13 and the centromere of chromosome7 (cen7) in liquid-based cytology specimens from 168 women enrolled in the Biopsy Study were determined by FISH. ...[more]

PMID: 23769811

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Project description:OBJECTIVE:To evaluate the performance of routine endocervical curettage (ECC) for diagnosing high-grade cervical intraepithelial neoplasia (CIN) 2 or worse and additional precancers not otherwise detected by ectocervical biopsies. METHODS:In a secondary analysis of the Biopsy Study, a cross-sectional study conducted between 2009 and 2012 at the University of Oklahoma Health and Sciences Center that found an incremental increase in detection of cervical precancers by multiple biopsies at colposcopy, ECC was performed in most women aged 30 years or older. Cervical intraepithelial neoplasia 2 or worse yield by ECC alone was evaluated in analyses stratified by cervical cytology (atypical squamous cells of undetermined significance [ASC-US] or low-grade squamous intraepithelial lesions [LSIL] compared with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions [ASC-H] or high-grade squamous intraepithelial lesions [HSIL] or worse), colposcopic impression (less than high-grade compared with high-grade), human papillomavirus (HPV)-16 infection status, whether the examination was satisfactory, and by ECC indications per the current guidelines for cervical cancer screening. The diagnostic value of ECC for detecting additional disease was evaluated by the number of lesion-directed ectocervical biopsies. RESULTS:Of the 204 women aged 30 years or older, 181 (88.7%) underwent ECC. Overall ECC detected 14.4% CIN 2 or worse (95% CI 10.0-20.2%). Endocervical curettage was more likely to find disease in the endocervix among women with high-grade cytology, positive HPV-16 infection, or high-grade colposcopic impressions (respective P values <.05). Among women with ASC-US or LSIL cytology, those with an unsatisfactory examination had a 13.0% CIN 2 or worse yield on ECC (95% CI 6.1-25.7); when colposcopic examination was normal or satisfactory with visible abnormal lesions, ECC detected less than 5% CIN 2 or worse in the endocervix. An ASC-H or HSIL or worse cytology was associated with a CIN 2 or worse yield of 25.8% by ECC (95% CI 16.6-37.9%). However, ECC found only 3.9% (95% CI 1.9-7.8%) additional CIN 2 or worse beyond the cumulative disease detected by up to four biopsies of visible acetowhite ectocervical lesions. Additional CIN 2 or worse yield by ECC increased when fewer lesion-directed biopsies were taken (P<.05). CONCLUSION:The additional yield of CIN 2 or worse by ECC in a colposcopy with up to four ectocervical biopsies was low. Based on our findings, we recommend routine ECC be performed in women aged 45 years old or older with HPV-16 infection and in any woman aged 30 years or older with HSIL or worse or ASC-H cytology, high-grade colposcopic impression, or ASC-US or LSIL cytology and an unsatisfactory examination. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT00339989.

Project description:BackgroundHuman papillomavirus 16 (HPV16) is an oncogenic virus responsible for the majority of invasive cervical cancer cases worldwide. Due to genetic modifications, some variants are more oncogenic than others. We analysed the HPV16 phylogeny in HPV16-positive cervical Desoxyribonucleic Acid (DNA) samples collected from South African and Mozambican women to detect the circulating lineages.MethodsPolymerase chain reaction (PCR) amplification of the long control region (LCR) and 300 nucleotides of the E6 region was performed using HPV16-specific primers on HPV16-positive cervical samples collected in women from South Africa and Mozambique. HPV16 sequences were obtained through Next Generation Sequencing (NGS) methods. Geneious prime and MEGA 11 software were used to align the sequences to 16 HPV16 reference sequences, gathering the A, B, C, and D lineages and generating the phylogenetic tree. Single nucleotide polymorphisms (SNPs) in the LCR and E6 regions were analysed and the phylogenetic tree was generated using Geneious Prime software.ResultsFifty-eight sequences were analysed. Of these sequences, 79% (46/58) were from women who had abnormal cervical cytology. Fifteen SNPs in the LCR and eight in the E6 region were found to be the most common in all sequences. The phylogenetic analysis determined that 45% of the isolates belonged to the A1 sublineage (European variant), 34% belonged to the C1 sublineage (African 1 variant), 16% belonged to the B1 and B2 sublineage (African 2 variant), two isolates belonged to the D1-3 sublineages (Asian-American variant), and one to the North American variant.ConclusionsThe African and European HPV16 variants were the most common circulating lineages in South African and Mozambican women. A high-grade squamous intraepithelial lesion (HSIL) was the most common cervical abnormality observed and linked to European and African lineages. These findings may contribute to understanding molecular HPV16 epidemiology in South Africa and Mozambique.

Project description:BackgroundWith the introduction of oncogenic Human Papillomavirus (HPV) testing into cervical screening there is a renewed focus on primary prevention among high-risk groups. To date, little is known about the effectiveness of this program, and the extent to which individual-level factors, such as psychosocial health and agency, may play a role. In particular, it is unclear if knowledge of one's oncogenic HPV status impacts on adherence behaviors amongst women with screening abnormalities. The purpose of this study was to identify if clinical, demographic or psychosocial factors predict non-adherence with recommended colposcopy follow-up.MethodsThis prospective pilot study included 145 women referred to a large Toronto colposcopy clinic between December, 2013 and September, 2014. Demographic, clinical and psychosocial characteristics were collected at three points in time: (1) at initial colposcopy consultation; (2) 4-6 weeks following initial consultation, and; (3) at time of follow-up appointment (within 12 months of initial consultation).ResultsOverall, 13% (n = 145) of the women were classified as non-adherent. Older women (OR = 0.73, p < 0.01) and those with higher-grade lesions (OR = 0.10, p < 0.01) were less likely to be non-adherent, whereas current smokers (OR = 22.46, p < 0.01) were more likely to be non-adherent. While not statistically significant, variation in rates of non-adherence amongst the various HPV status groups (untested; 15.3%, HPV positive; 5.3%, HPV negative; 6.7%) warrants further study.ConclusionFindings of this study indicate that younger women, those with higher-grade lesions and current smokers were more likely to be non-adherent to recommended colposcopy follow-up. While HPV status did not reach statistical significance, the direction of this finding suggests that testing for HPV may have a positive reinforcing role on adherence to follow-up. The direction of this finding warrants further study, and potentially a practical clinical goal as HPV testing for women becomes standard of care.

Project description:ObjectiveThe aim of the study was to survey obstetrician-gynecologists' cervical cancer screening practices and management of cervical abnormalities to ascertain adherence to guidelines.MethodsFrom January to July 2019, obstetrician-gynecologists at 5 St. Louis area hospitals were surveyed online about cervical cancer screening and management practices through 13 clinical vignettes. Survey scores and the American Society of Colposcopy and Cervical Pathology (ASCCP) app use were compared using Mann-Whitney tests.ResultsWhen screening 30- to 65-year-old participants, 114 (98%) of the 116 total participants used co-testing, but only 71 (61%) screened at 5-year intervals. None used primary human papillomavirus (HPV) testing. For 21- to 29-year-old participants, 17 (15%) screened with annual cytology, whereas 14 (12%) used annual or every 3-year co-testing. Forty eight (41%) screened younger than 21 years, regardless of risk factors or only if immunocompromised. Eleven (9%) continued screening after total hysterectomy for benign indications. Only 2 (2%) responded to all clinical vignettes in adherence to guidelines. More than 30% of participants would pursue unnecessary HPV testing and/or loop electrosurgical excision procedure for persistent low-grade cytology. Fifty eight (48%) incorrectly reported hysterectomy as management for adenocarcinoma in situ on biopsy. Participants would undertreat young women with high-grade abnormalities including high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 3 (48, 41%) and high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 1 (65, 56%). Forty one (35%) reported exiting women from screening prematurely. The median score for participants using the ASCCP app was significantly greater than those who did not (79% vs 71%, p = .002).ConclusionsMidwestern obstetrician-gynecologists' adherence to the guidelines for cervical cancer screening and management of abnormal results is suboptimal. Although co-testing for women aged 30-65 years has been broadly adopted, primary HPV testing has not. Physicians overscreen, overtreat low-grade lesions, and undertreat high-grade lesions in young women.

Project description:In women aged ≥ 30 years, Human Papillomavirus testing will replace cytology for primary cervical screening. We compared Hybrid Capture 2 (HC2), cobas, CLART, and APTIMA HPV assays with cytology on 2869 SurePath samples from women undergoing routine screening at 30-65 years in Copenhagen, Denmark. Women with cytological abnormalities were managed according to routine recommendations, with 92% completeness. Those with cytology-normal/HPV-positive samples (on any of the four assays) were invited for repeated cytology and HPV testing in 1.5 year, and 58% had additional testing. HPV testing detected more ≥ CIN3 than cytology (HC2: 35, cobas, CLART: 37, APTIMA: 34, cytology: 31), although statistically the differences were not significant. Cobas and CLART detected significantly more ≥ CIN2 than cytology (cobas, CLART: 49, cytology: 39). The proportion of women with false-positive test results (positive test results without ≥ CIN3) varied between 3.3% with cytology and 14.9% with cobas. All HPV assays led to significantly more false-positive tests, whereas compared to HC2 cobas and CLART were associated with a significantly higher and APTIMA with a significantly lower proportion. Detection of CIN1 was particularly increased for the three DNA assays. With APTIMA combined with cytological triage, about 20% more women were referred for colposcopy than with cytology screening. With the three DNA assays, the increase was ≥ 50%. The number of women with repeated testing was twice as high with APTIMA and almost five times as high with cobas compared to cytology. To our knowledge, Horizon was the only study set in routine practice that compared more than two HPV assays in the same women while also ascertaining the histological status of women with normal cytology/HPV-positive test results. HPV-based screening of Danish women aged 30-65 detected more high-grade CIN but decreased the screening specificity, and increased the demand for additional testing.

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Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results.

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Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results.

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