Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study

McCredie, Margaret; Sharples, Katrina; Paul, Charlotte; Baranyai, Judith; Medley, Gabriele; Jones, Ronald W.; Skegg, D. C. G.

doi:10.1016/s1470-2045(08)70103-7

Cited by 903 publications

(719 citation statements)

References 19 publications

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“…These results correspond to the finding that only a subset of CIN2/3 will progress to cancer over a long time period [18,19]. Previous studies on copy number changes and DNA methylation levels of only a few genes also showed a cancer-like profile in only a subset of CIN2/3 lesions [11,14,20,21].…”

Section: Discussionsupporting

confidence: 87%

Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer

et al. 2018

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Cervical cancer development following a persistent infection with high-risk human papillomavirus (hrHPV) is driven by additional host-cell changes, such as altered DNA methylation. In previous studies, we have identified 12 methylated host genes associated with cervical cancer and pre-cancer (CIN2/3). This study systematically analyzed the onset and DNA methylation pattern of these genes during hrHPV-induced carcinogenesis using a longitudinal in vitro model of hrHPV-transformed cell lines (n = 14) and hrHPV-positive cervical scrapings (n = 113) covering various stages of cervical carcinogenesis. DNA methylation analysis was performed by quantitative methylation-specific PCR (qMSP) and relative qMSP values were used to analyze the data. The majority of genes displayed a comparable DNA methylation pattern in both cell lines and clinical specimens. DNA methylation onset occurred at early or late immortal passage, and DNA methylation levels gradually increased towards tumorigenic cells. Subsequently, we defined a so-called cancer-like methylation-high pattern based on the DNA methylation levels observed in cervical scrapings from women with cervical cancer. This cancer-like methylation-high pattern was observed in 72% (38/53) of CIN3 and 55% (11/20) of CIN2, whereas it was virtually absent in hrHPV-positive controls (1/26). In conclusion, hrHPV-induced carcinogenesis is characterized by early onset of DNA methylation, typically occurring at the pre-tumorigenic stage and with highest DNA methylation levels at the cancer stage. Host-cell DNA methylation patterns in cervical scrapings from women with CIN2 and CIN3 are heterogeneous, with a subset displaying a cancer-like methylation-high pattern, suggestive for a higher cancer risk.

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Section: Discussionsupporting

confidence: 87%

Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer

et al. 2018

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“…Timely follow-up of patients with HSIL Pap results is regarded as mandatory because of the high risk of treatable potentially progressive high-grade squamous intraepithelial lesions 35 and because of the risk of an underlying asymptomatic cervical carcinoma. 4,5 Accordingly, the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88) requires laboratories to monitor patients with HSIL Pap results with no recorded follow-up.…”

Section: Discussionmentioning

confidence: 99%

Histopathologic follow‐up and human papillomavirus DNA test results in 290 patients with high–grade squamous intraepithelial lesion papanicolaou test results

Gao

Austin

Zhao

2011

Cancer Cytopathology

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BACKGROUND:The study documents histopathologic outcomes and high‐risk (hr) human papillomavirus (HPV) test results in a large cohort of patients with high‐grade squamous intraepithelial lesion (HSIL) liquid‐based cytology (LBC) Pap test results.METHODS:A total of 352 patients with HSIL results (338 cervical and 14 vaginal) who had hrHPV testing and 290 patients with biopsy follow‐up were studied. hrHPV detection rates were compared at different ages, with or without an endocervical/transformation zone sample (EC/TZS), and for cervical and vaginal HSIL Pap smears. Histopathologic follow‐up findings were also compared. hrHPV‐negative HSIL slides were re‐evaluated in a blinded manner.RESULTS:A total of 325 of 338 (96.2%) cervical HSIL and 12 of 14 (87.5%) vaginal HSIL tested hrHPV‐positive. A total of 271 of 281 (96.4%) EC/TZS‐positive cervical HSIL and 54 of 57 (94.7%) EC/TZS‐negative cervical HSIL tested hrHPV‐positive. The percentage of hrHPV‐positive HSIL declined slightly with increasing age. 197 of 273 (72.3%) hrHPV‐positive cervical HSIL had histopathologic cervical intraepithelial neoplasia (CIN) 2/3+ follow‐up, including 8 squamous carcinomas, compared with 4 of 12 (33.3%) hrHPV‐negative HSIL with CIN2/3 (no carcinomas). 167 of 241 (69.2%) EC/TZS‐positive HSIL had CIN2/3+ follow‐up, compared with 34 of 44 (77.3%) EC/TZS‐negative HSIL. Equivocal HSIL morphology characterized some HPV‐negative HSIL without CIN2/3+ follow‐up.CONCLUSIONS:hrHPV was detected in LBC vials from 96.2% of 338 cervical HSIL and 85.7% of 14 vaginal HSIL. CIN2/3+ was significantly more likely with hrHPV‐positive cervical HSIL than with hrHPV‐negative cervical HSIL. Presence or absence of an EC/TZS did not significantly impact HSIL hrHPV or CIN2/3+ rates. Some hrHPV‐negative HSIL cases may represent HSIL cytologic mimics. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.

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“…A cervical sample was collected from all of the patients using a cytobrush which was transferred to PreservCyt solution (Hologic Corp, Marlborough, MA, USA) for ThinPrep liquid-based cytology and high-risk HPV testing. Exclusion criteria were: (1) previous history of cervical cancer, (2) treatment for HSIL/CIN2-3 performed within the previous 3 years; (3) immunosuppression, (4) pregnancy, and (5) insufficient tissue showing LSIL/CIN1 for immunohistochemical analysis. All patients signed informed consent, and the study was approved by the Institutional Ethical Review Board.…”

Section: Study Design and Patient Selectionmentioning

confidence: 99%

“…2 High-grade SIL/CIN grades 2-3 (HSIL/CIN2-3) are considered the immediate precursor of cervical cancer. 3 In contrast, about 80% of low-grade SIL/CIN1 (LSIL/CIN1) are transient lesions that generally spontaneously regress in 1-2 years. 1,[4][5][6][7] Accordingly, the management of HSIL/CIN2-3 generally involves the excision of the lesion and the transformation zone to prevent the development of cervical cancer, whereas the management of LSIL/CIN1 is conservative, being based on clinical follow-up.…”

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confidence: 99%

p16 staining has limited value in predicting the outcome of histological low-grade squamous intraepithelial lesions of the cervix

et al. 2016

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In order to evaluate the usefulness of p16 staining in predicting the outcome of histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL/CIN1) we prospectively recruited all the patients referred to colposcopy from 2003 to 2011 due to abnormal screening test results and diagnosed with LSIL/CIN1 at biopsy (n = 507). All biopsies were stained for p16 and re-evaluated after three years by the same gynecological pathologist using the LAST criteria. Follow-up was conducted every 6 months and included a Pap test (liquid-based cytology), high-risk human papillomavirus testing (Hybrid Capture 2 test), and colposcopy. The mean follow-up was 28 months. An outcome diagnosis of HSIL was defined as a histological diagnosis of highgrade SIL/CIN (HSIL/CIN2-3). The diagnosis of LSIL/CIN1 was confirmed in 416 out of 507 biopsies (82%), whereas 58 (11%) were reclassified as negative and 33 (6%) as HSIL/CIN2-3. During follow-up, 86/507 women initially diagnosed with LSIL/CIN1 (17%) showed an outcome diagnosis of HSIL/CIN2-3, with the rate of HSIL final diagnosis of 3% (2/58) in the women with biopsies reclassified as negative, 17% (70/416) in the group with confirmed LSIL and 42% (14/33) in the women with biopsies reclassified as HSIL (Po 0.001). p16 was positive in 245/507 patients (48%) and in 210/416 patients (50%) with confirmed LSIL/CIN1 at re-evaluation. Although positive p16 immunostaining was associated with risk of HSIL/CIN2-3 outcome in the multivariate analysis (Hazard ratio (HR) 1.9; 95% confidence interval (CI): 1.2-3.1; P = 0.009) in the overall group of patients with LSIL/CIN1, this association was not verified in the subset of patients with confirmed LSIL/CIN1 after re-evaluation (HR: 1.6; 95% CI: 0.9-2.6; P = 0.095). In conclusion, in LSIL/CIN1 lesions p16 should be limited to equivocal cases in which HSIL/CIN2 is included in the differential diagnosis since it has low value in clinical practice as a marker of progression of LSIL/CIN1.

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Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study

Cited by 903 publications

References 19 publications

Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer

Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer

Histopathologic follow‐up and human papillomavirus DNA test results in 290 patients with high–grade squamous intraepithelial lesion papanicolaou test results

p16 staining has limited value in predicting the outcome of histological low-grade squamous intraepithelial lesions of the cervix

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