scholarly journals Long-term observational approach in women with histological diagnosis of cervical low-grade squamous intraepithelial lesion: an Italian multicentric retrospective cohort study

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e024920 ◽  
Author(s):  
Andrea Ciavattini ◽  
Matteo Serri ◽  
Jacopo Di Giuseppe ◽  
Carlo Antonio Liverani ◽  
Barbara Gardella ◽  
...  

ObjectiveTo evaluate the risk of progression to high-grade squamous intraepithelial lesion (HSIL) (CIN2-3) or invasive cancer in women with histopathological diagnosis of low-grade squamous intraepithelial lesion (LSIL) (CIN1), managed in a long-term observational approach up to 5 years.DesignRetrospective cohort study.SettingFour tertiary referral hospital.Participants434 women with adequate colposcopy and complete colposcopic charts were included in the present analysis. Women with glandular lesions on the referral cytology or previous diagnosis of cervical dysplasia or invasive cervical cancer or with synchronous vaginal, or with HIV infection or immunodepression were excluded.Primary and secondary outcome measuresThe main study outcome was the rate of progression to histopathological HSIL (CIN2-3) or invasive cancer at any time during 5 years of follow-up. The possible risk factors were also evaluated. As secondary outcome, we analysed the possible risk factors at the 24-month evaluation for histopathological HSIL (CIN2-3) or invasive cancer progression between 2 and 5 years from initial diagnosis.ResultsA progression to histopathological HSIL (CIN2-3) was found in a total of 32 (7.4%) cases during 5 years of follow-up. A histopathological diagnosis of HSIL (CIN3) was found in four patients (0.9%) and no case of invasive cancer was detected. High-grade cytology at inclusion and the presence of a positive high-risk human papillomavirus (HR-HPV) DNA test at 2 years from inclusion maintained a significant correlation with the risk of histopathological progression to HSIL (CIN2-3).ConclusionsThe results of our study showed a low rate (7.4%) of histopathological progression to HSIL (CIN2-3) in women with LSIL (CIN1) diagnosis during long-term follow-up up to 5 years. In case of positive HR-HPV DNA test at the 2 years evaluation an excisional treatment could be the preferred choice to prevent progression to HSIL (CIN2-3) in the following years, preferring a continuation of follow-up in case of HR-HPV DNA negative result.

2011 ◽  
Vol 21 (1) ◽  
pp. 79-85 ◽  
Author(s):  
Maria Nasioutziki ◽  
Angelos Daniilidis ◽  
Kostos Dinas ◽  
Maria Kyrgiou ◽  
George Valasoulis ◽  
...  

Aim:To evaluate the role of p16INK4a immunoexpression and human papillomavirus (HPV) DNA test for the detection of dyskaryotic cells in high-risk women.Materials and Methods:This work was a retrospective diagnostic study conducted in the University Hospital of Thessaloniki from January to December 2008. The subjects were women with current or previous HPV infection and current or previous cervical intraepithelial lesion (with or without treatment) or clinical warts. All liquid-based cytological samples were tested for P16INKa and HPV DNA test. The accuracy parameters used for the outcome included sensitivity, specificity, and positive predictive value.Results:A total of 226 women were included; the mean age was 29 years. Expression of p16INK4a was detected in the cytological samples of 13% of the negative cases, 44% of the cases of atypical squamous cells of undetermined significance, 46% of the cases of low-grade squamous intraepithelial lesion, and 78% of the cases of high-grade squamous intraepithelial lesion. A total of 91 women tested positive for high-risk HPV infection, and 54 of those had p16INK4a-positive staining reaction cells. The concordance between the 2 tests, HPV DNA and p16, was 59% regarding infection-positive cases. Diffuse strong parabasal p16INK4a immunostaining (nuclear score >2) was observed in 17 cases of the abnormal cytological findings (atypical squamous cells of undetermined significance, 2 cases; low-grade squamous intraepithelial lesion, 8 cases; high-grade squamous intraepithelial lesion, 7 cases). Colposcopy-directed biopsies were used as the criterion standard for the detection of cervical intraepithelial neoplasia in 91 women. The sensitivity of p16INK4a was 95% and the specificity was 92%, whereas the sensitivity of high-risk HPV was 100% and the specificity was 78%. The positive predictive value of p16INK4a was 71%, whereas that of HPV DNA was 44%.Conclusion:The findings suggest that p16INK4a immunostaining can improve the accuracy of cytological examination and HPV DNA test and may be particularly useful in the triage of low-grade lesions.


2011 ◽  
Vol 135 (12) ◽  
pp. 1545-1549 ◽  
Author(s):  
Mona Bansal ◽  
R Marshall Austin ◽  
Chengquan Zhao

Context.—Data on high-risk human papillomavirus (hrHPV) DNA test results in vaginal, liquid-based cytology (LBC) specimens and corresponding cytologic and histopathologic correlation data are limited. Objective.—To analyze follow-up correlation data associated with vaginal (after hysterectomy) low-grade squamous intraepithelial lesion (LSIL) LBC and hrHPV test results. Design.—Hospital records were searched for vaginal LSIL LBC and hrHPV results between July 1, 2005, and July 30, 2009. Histopathologic and Papanicolaou test follow-up correlation data were analyzed. Results.—During the study period, 2892 patients with test results from both posthysterectomy vaginal LBC and hrHPV were identified: 148 (5.1%) of the patients had vaginal Papanicolaou test results reported as LSIL, with hrHPV detected in 113 of the 148 patients (76.4%). Of 148 patients, 59 of those with vaginal LSIL including 48 (81.4%) with positive HPV testing and 11 (18.6%) with negative HPV testing results had a follow-up vaginal biopsy. Histopathologic vaginal intraepithelial neoplasia (VAIN) 2/3 was diagnosed in 7 of 59 patients (11.9%) with biopsies. In all 7 patients who were diagnosed with VAIN 2/3, hrHPV was detected in the LBC vial. No VAIN 2/3 diagnoses were documented in the biopsy specimens from the 11 patients with hrHPV− LSIL Papanicolaou test results. Histopathologic VAIN 2/3 was diagnosed from vaginal biopsies in 7 of the 48 patients (14.6%) with vaginal hrHPV+ LSIL test results. Conclusions.—Sensitivity and specificity of hrHPV test results associated with histopathologic follow-up diagnoses of VAIN 2/3 in patients with vaginal LSIL results were 100% and 21.2%, respectively. The positive predictive value of a vaginal hrHPV+ LSIL result for a subsequent histopathologic VAIN 2/3 diagnosis was 14.6%. No cases of VAIN 2/3 were diagnosed in the 11 patients with vaginal hrHPV− LSIL results. Correlations of vaginal cytologic, histopathologic, and human papillomavirus findings were quite similar to correlation findings previously reported in older women with cervical LSIL test results.


CytoJournal ◽  
2007 ◽  
Vol 4 ◽  
pp. 7 ◽  
Author(s):  
Vinod B Shidham ◽  
Nidhi Kumar ◽  
Raj Narayan ◽  
Gregory L Brotzman

Background Cervical smears exhibiting unequivocal features of ‘low grade squamous intraepithelial lesion’ (LSIL) are occasionally also admixed with some cells suspicious for, but not diagnostic of, ‘high grade squamous intraepithelial lesion’ (HSIL). Only a few studies, mostly reported as abstracts, have evaluated this concurrence. In this study, we evaluate the current evidence that favors a distinct category for “LSIL, cannot exclude HSIL” (LSIL-H), and suggest a management algorithm based on combinations of current ASCCP guidelines for related interpretations. Methods We studied SurePath™ preparations of cervical specimens from various institutions during one year period. Cytohisto correlation was performed in cases with cervical biopsies submitted to our institution. The status of HPV DNA testing was also noted in some LSIL-H cases with biopsy results. Results Out of 77,979 cases 1,970 interpreted as LSIL (1,523), LSIL-H (146), ‘atypical squamous cells, cannot exclude HSIL’ (ASC-H) (109), and HSIL (192) were selected. Concurrent biopsy results were available in 40% (Total 792 cases: 557 LSIL, 88 LSIL-H, 38 ASCH, and 109 HSIL). Biopsy results were grouped into A. negative for dysplasia (ND), B. low grade (HPV, CIN1, CIN1 with HPV), and C. high grade (CIN 2 and above). The positive predictive values for various biopsy results in relation to initial cytopathologic interpretation were: a. LSIL: (557 cases): ND 32% (179), low grade- 58% (323), high grade- 10% (55); b. LSIL-H: (88 cases): ND 24% (21), low grade- 43% (38), high grade- 33% (29); c. ASCH: (38 cases): ND 32% (12), low grade- 37% (14), high grade- 31% (12); d. HSIL (109 cases): ND 5% (6), low grade 26% (28), high grade 69% (75). The patterns of cervical biopsy results in cases reported as LSIL-H were compared with that observed in cases with LSIL, ASC-H, and HSIL. 94% (32 of 34) of LSIL-H were positive for high risk (HR) HPV, 1 was negative for HR HPV but positive for low risk (LR), and 1 LSIL-H was negative for HR and LR both. Conclusion LSIL-H overlapped with LSIL and ASC-H, but was distinct from HSIL. A management algorithm comparable to ASC-H and HSIL appears to be appropriate in LSIL-H cases.


2012 ◽  
Vol 136 (10) ◽  
pp. 1259-1261 ◽  
Author(s):  
Benjamin L. Witt ◽  
Rachel E. Factor ◽  
Elke A. Jarboe ◽  
Lester J. Layfield

Context.—Loop electrosurgical excision procedure (LEEP) is a therapeutic option following biopsy diagnosis of high-grade squamous intraepithelial lesion (HSIL). Most LEEPs will confirm the HSIL biopsy diagnosis but a number of them will not. Such negative findings suggest the possibility of an incorrect biopsy diagnosis, removal of the lesion by biopsy, or insufficient LEEP sampling. Objective.—To determine the frequency of negative LEEP findings following HSIL biopsies and better understand the clinical significance of negative LEEP findings. Design.—The Department of Pathology's records were searched for all patients undergoing LEEP excision who had prior cervical biopsies and subsequent clinical follow-up. Results.—Three hundred seventy-eight women were found who had index biopsies, subsequent LEEPs, and clinical follow-up averaging 25.8 months. Three hundred six women had HSIL on biopsy with 223 (73%) showing HSIL on LEEP. Seventy-three (24%) LEEPs in women with HSIL index biopsy results yielded negative findings or disclosed low-grade squamous intraepithelial lesion (LSIL). Twenty-nine of 223 patients (13%) with an HSIL result both on biopsies and LEEPs had HSIL on biopsy and/or excisional clinical follow-up. Seven of 73 patients (10%) with positive (HSIL) biopsy results but negative LEEP findings or LSIL had HSIL on biopsy and/or excisional follow-up. Conclusions.—Twenty-four percent of patients with HSIL on biopsy had negative findings or LSIL on LEEP. There is no statistical difference in development of HSIL after LEEP for those with positive biopsy and positive LEEP results (13%) versus positive biopsy and negative LEEP results (10%). The occurrence of a negative LEEP finding following a positive biopsy finding was frequent (24%) and does not portend a different clinical follow-up from a positive biopsy and positive LEEP result.


2011 ◽  
Vol 2011 ◽  
pp. 1-9
Author(s):  
Katsunari Ishida ◽  
Makoto Nagasaki ◽  
Masayuki Kobayashi ◽  
Tatsushi Nakagawa ◽  
Toru Nabika ◽  
...  

To examine the diagnostic utility for squamous intraepithelial lesion (SIL) by cytological in situ hybridization (c-ISH) for the human papillomavirus using liquid-based cytology specimens, we investigated c-ISH signal patterns in the cases of low-grade SIL (LSIL), atypical squamous cells of undetermined significance (ASC-US), and high-grade SIL (HSIL). Episomal (E) and/or integrated (I) signals were observed. Two signal patterns (E≧I or I>E) were obtained by counting the number of E+ or I+ cells. E≧I was specific to LSIL and ASC-US (10/12); I>E, to HSIL (9/11) (P<0.01, χ2 test), suggesting significant utility of c-ISH in diagnosing SIL. In the cell fraction, E≧I in large cells was dominant in LSIL. Two cases of I>E in large cells of LSIL showed HPV persistence and/or progression during follow-up. Thus, c-ISH is useful in routine testing for diagnosing cervical dysplastic lesions, especially for detecting LSIL suspected for progression.


2009 ◽  
Vol 127 (5) ◽  
pp. 266-269 ◽  
Author(s):  
Fernanda Rangel da Veiga ◽  
Fábio Bastos Russomano ◽  
Maria José de Camargo ◽  
Aparecida Cristina Sampaio Monteiro ◽  
Aparecida Tristão ◽  
...  

CONTEXT AND OBJECTIVE: Cervical cancer is a serious public health problem in Brazil. For patients with unsatisfactory colposcopic examinations without visible lesions, but with cervical cytological tests suggesting high-grade squamous intraepithelial lesion (HSIL), the national recommendation is to repeat cervical cytological tests after three months. Our aim was to assess the prevalence of HSIL and cancer among patients with initial cervical cytological tests suggestive of HSIL but with unsatisfactory colposcopic examinations without visible lesions, in order to contribute towards the discussion regarding a more effective clinical approach that might diminish the likelihood of patient abandonment of follow-up before appropriate diagnosis and treatment. DESIGN AND SETTING: Cross-sectional study in Colposcopy Clinic of IFF/Fiocruz. METHOD: Patients admitted between December 1989 and April 2007 with cytological diagnoses of HSIL but with unsatisfactory colposcopic examinations without visible lesions underwent cervical cone biopsy. RESULTS: Sixty-five such patients were included, comprising 33.8% with HSIL and 4.6% with cancer, confirmed histologically. The other patients presented low-grade squamous intraepithelial lesion (26.1%), glandular dysplasia (1.5%) and absence of disease (33.8%). CONCLUSION: The observed prevalence of cancer and HSIL does not seem to be enough to justify immediate referral for cone biopsies to investigate the cervical canal in these cases. The findings suggest that the recommendation of repeated cytological tests following an initial one with HSIL, among patients with unsatisfactory colposcopic examinations without visible lesions, is appropriate in our setting. Efforts are needed to ensure adherence to follow-up protocols in order to reduce the chances of losses.


2003 ◽  
Vol 127 (9) ◽  
pp. 1169-1175 ◽  
Author(s):  
Alice Lytwyn ◽  
John W. Sellors ◽  
James B. Mahony ◽  
Dean Daya ◽  
William Chapman ◽  
...  

Abstract Context.—Although human papillomavirus (HPV) testing may aid in managing low-grade abnormality on screening cervical cytology, patient compliance with repeat testing programs requires consideration. Objectives.—To determine effectiveness and costs of repeated Papanicolaou (Pap) test and oncogenic HPV testing for detecting cervical intraepithelial neoplasia 2 or 3. Design.—We conducted a randomized controlled trial of combined Pap test and cervical HPV testing by Hybrid Capture 1 test compared with Pap test alone; tests were performed every 6 months for up to 2 years. The study end point was colposcopic examination performed on all women at 2 years, or earlier if an HPV test was positive or if a Pap test showed high-grade squamous intraepithelial lesion. Setting.—Sixty-six community family practices. Participants.—Two hundred fifty-seven women with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion on screening cervical cytology. Main Outcome Measures.—Detection of histologically confirmed cervical intraepithelial neoplasia 2 or 3, fully allocated costs, and loss to follow-up. Results.—Combined Pap test and HPV testing detected 11 (100%) of 11 cases of cervical intraepithelial neoplasia 2/3, whereas Pap test alone detected 7 (63.6%) of these 11 cases (P = .14); corresponding specificities were 39 (46.4%) of 84 and 45 (71.4%) of 63 (P = .005). The cost-effectiveness ratio was Can $4456 per additional case of high-grade cervical intraepithelial neoplasia. Sixty-nine (26.8%) of the 257 women (24.6% combined group vs 29.1% Pap test only group, P = .41) defaulted from testing or from colposcopy when referred with an abnormal result. Conclusions.—Combined testing was more costly but may detect more cases of cervical intraepithelial neoplasia 2/3 than Pap test alone. However, poor adherence limits usefulness of a management strategy that requires repeated follow-up.


2018 ◽  
Vol 146 (5) ◽  
pp. 612-618 ◽  
Author(s):  
M. T. Bruno ◽  
M. Ferrara ◽  
V. Fava ◽  
G. Barrasso ◽  
M. M. Panella

AbstractHuman papillomavirus (HPV) testing is used in the triage of women with a borderline smear result. The efficiency of testing women with a low-grade squamous intraepithelial lesion (LSIL) and atypical squamous cells of undetermined significance (ASCUS) is less clear. For this reason we used a new HPV test that detects E6/E7 messenger RNA (mRNA), which might have a higher specificity. The objective of this prospective study was to assess whether HPV E6/E7 mRNA positivity in women with ASCUS and LSIL at baseline, is able to predict those women who have a high risk of developing a histological cervical intraepithelial neoplasia (CIN2) or worse lesion. We took into consideration the women's age and HPV DNA genotype and followed them up for 3 years. Cervical samples from women with high-risk HPV (HR-HPV) DNA-positive ASCUS (n = 90) or LSIL (n = 222) were tested for the presence of HR-HPV E6/E7 mRNA and the women were monitored for the development of histopathologically verified CIN2+. Thirteen patients with ASCUS and 17 with LSIL did not complete follow-up. All patients with LSIL and ASCUS, enrolled in this study, had confirmed lesions at the colposcopic examination. Follow-up was available for 312 women, 193 were positive in the HR-HPV DNA test and 93 had a HPV E6/E7 mRNA positive test. Finally, 22 women positive in the HPV DNA test for high-risk genotypes and with positive E6/E7 mRNA had a histologically confirmed CIN2+. Only two cases with negative HPV E6/E7 mRNA had CIN2+. The study shows that women positive in the HPV E6/E7 mRNA test have a greater risk of malignant progression of cervical lesions and therefore deserve greater attention and earlier check-ups.


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