scholarly journals A multicentre, prospective, randomised controlled trial to evaluate hexaminolevulinate photodynamic therapy (Cevira®) as a novel treatment in patients with high grade squamous intraepithelial lesion: APRICITY Phase 3 study protocol

Author(s):  
Fei Chen ◽  
Zoltán Novák ◽  
Christian Dannecker ◽  
Long Sui ◽  
Youzhong Zhang ◽  
...  

AbstractIntroductionHigh-risk human papilloma virus (HPV)-associated cervical cancer is the fourth most common cancer in women worldwide. Current treatments of high grade squamous intraepithelial lesion (HSIL) of the cervix are based on invasive surgical interventions, compromising cervical competence and functionality.ObjectiveAPRICITY is a multicentre, prospective, double-blind, randomised controlled Phase 3 study further evaluating the efficacy and safety of Cevira®, an integrated drug- and light-delivery device for hexaminolevulinate photodynamic therapy, which shows promise as a novel, non-invasive therapy for women with HSIL.Methods and analysisPatients with biopsy-confirmed HSIL histology are invited to participate in the study currently being conducted at 47 sites in China and 25 sites in Ukraine, Russia and European Union. The aim is to include at least 384 patients which will be randomised to either Cevira® or placebo group (2:1). All patients will be assessed 3 months after first treatment and a second treatment will be administered in patients who are HPV positive or have at least low grade squamous intraepithelial lesion (LSIL). Primary endpoint is the proportion of the responders at 6 months after first treatment. Secondary efficacy endpoints and safety endpoints will be assessed at 6 months, and data for secondary performance endpoints for Cevira® device will be collected at 3 months and 6 months, in case second treatment was administered. All patients in the Cevira® group will be enrolled in an open, long-term extension study following patients for further 6 months to collect additional efficacy and safety data (study extension endpoints).ConclusionDue to its non-invasiveness and convenient application, Cevira® may be a favourable alternative to surgical methods in treatment of patients with HSIL.Ethics and disseminationThe study was approved by the ethics committee of the Peking Union Medical College Hospital and Hannover Medical University, Germany. Findings will be disseminated through peer review publications and conference presentations.Trial registration numberclinicaltrials.govNCT04484415

2020 ◽  
Vol 16 (1) ◽  
pp. 18-22
Author(s):  
Eronmwon E. Gbinigie ◽  
Joshua Fogel ◽  
Maggie Tetrokalashvili

Background: Clinicians commonly perform colposcopy directed biopsies on patients with low grade squamous intraepithelial lesion (LSIL) on PAP cytology even when not consistent with clinical guidelines. Objective: We study the association of PAP cytology screening results with cervical intra-epithelia neoplasia (CIN) 2-3 high-grade dysplasia, as confirmed by colposcopy-directed biopsy. Methods: A retrospective study of 263 women with an abnormality on the PAP smear. Multinomial logistic regression was performed with predictors of PAP cytology screening results with the outcome variable of colposcopy-directed biopsy. Results: High grade squamous intraepithelial lesion (HSIL) had significantly increased relative risk for CIN 2-3 (RR: 9.85, 95% CI: 1.84, 52.79, p=0.008). LSIL was not significantly associated with CIN 2-3. In the comparisons of negative with CIN-1, both HSIL and LSIL were not significantly associated with a negative biopsy. Conclusion: HSIL is associated with cervical dysplasia of CIN 2-3 while LSIL is not associated with cervical dysplasia of CIN 2-3. We do not recommend routine biopsies in patients with LSIL cytologic abnormalities unless additional compelling factors exist.


2018 ◽  
Vol 143 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Barbara A. Crothers ◽  
Mohiedean Ghofrani ◽  
Chengquan Zhao ◽  
Leslie G. Dodd ◽  
Kelly Goodrich ◽  
...  

Context.— Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging. Objective.— To determine diagnostic concordance for biopsy-proven low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Papanicolaou test slides in the College of American Pathologists PAP Education program. Design.— We analyzed 121 059 responses from 4251 LSIL and HSIL slides for the interval 2004 to 2013 using a nonlinear mixed-model fit for reference diagnosis, preparation type, and participant type. We evaluated interactions between the reference diagnosis and the other 2 factors in addition to a repeated-measures component to adjust for slide-specific performance. Results.— There was a statistically significant difference between misclassification of LSIL (2.4%; 1384 of 57 664) and HSIL (4.4%; 2762 of 63 395). There was no performance difference between pathologists and cytotechnologists for LSIL, but cytotechnologists had a significantly higher HSIL misclassification rate than pathologists (5.5%; 1437 of 27 534 versus 4.0%; 1032 of 25 630; P = .01), and both were more likely to misrepresent HSIL as LSIL (P < .001) than the reverse. ThinPrep LSIL slides were more likely to be misclassified as HSIL (2.4%; 920 of 38 582) than SurePath LSIL slides (1.5%; 198 of 13 196), but conventional slides were the most likely to be misclassified in both categories (4.5%; 266 of 5886 for LSIL, and 6.5%; 573 of 8825 for HSIL). Conclusions.— More participants undercalled HSIL as LSIL (false-negative) than overcalled LSIL as HSIL (false-positive) in the PAP Education program, with conventional slides more likely to be misclassified than ThinPrep or SurePath slides. Pathologists and cytotechnologists classify LSIL equally well, but cytotechnologists are significantly more likely to undercall HSIL as LSIL than are pathologists.


2020 ◽  
Vol 3 (2) ◽  
pp. 392-394
Author(s):  
Alina Karna ◽  
Nisha Sharma

Adenoid basal carcinoma of the uterine cervix is a rare low-grade tumor and its cell origin is still obscure. Adenoid basal carcinoma can be confused with adenoid basal hyperplasia, adenoid cystic carcinoma, and basaloid squamous cell carcinoma of the cervix. We present here a case of a 59 year-old-female who initially presented with a high-grade squamous intraepithelial lesion on Pap smear. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histopathology revealed focal invasive adenoid basal carcinoma with extensive areas of a high-grade squamous intraepithelial lesion involving the endocervical gland. The immunohistochemical stain was positive for p16.


2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Sefa Kelekci ◽  
Emre Destegül ◽  
Servet Gençdal ◽  
Emre Ekmekçi ◽  
Hüseyin Aydoğmuş ◽  
...  

<p>This study evaluates the statistical analysis of cervicovaginal smear results at postmenopausal period accompanied by literature. Cervicovaginal smear results of 894 postmenopausal women were evaluated retrospectively according to the 2001 Bethesda system (BS) in Adana Numune Training and Research Hospital of Obstetrics and Gynecology Clinic from 2007–2010. The study found, normal results on 287 patients (32.1%), benign findings on 556 patients (62.2%), abnormal epithelial cell changes on 48 patients (5.36%) and malignant changes on 3 patients (0.33%). The abnormal epithelial changes were observed to be atypical cells of undetermined significance (ASC-US) for 22 patients (2.46%), <a href="http://medical-dictionary.thefreedictionary.com/high-grade+squamous+intraepithelial+lesion">low-grade squamous intraepithelial lesion</a> (LSIL) for 11 patients (1.23%), <a href="http://medical-dictionary.thefreedictionary.com/high-grade+squamous+intraepithelial+lesion">high-grade squamous intraepithelial lesion</a> (HSIL) for 7 patients (0.78%), findings that cannot exclude a high-grade squamous intraepithelial lesion (ASC-H) for 6 patients (0.55%) and atypical glandular cells-not otherwise specified (AGC-NOS) for 2 patients (0.22%). Malignant results were 2 squamous cell carcinomas (SCC) (0.22%) and 1 adenocarcinoma (ACC) (0.11%). Cervical cancer screening programs should be expanded and Pap smear screening should be applied to all postmenopausal women. The longer time span involved from premalignant lesions to cancer improves our chance for the diagnosis and treatment. As the incidence of invasive cancer increases in menopausal period, gynecological smear examination and regular check-up are crucial. A high rate of abnormalities of epithelial cells was detected in this study.</p><p> </p>


2006 ◽  
Vol 130 (4) ◽  
pp. 456-459
Author(s):  
Andrew A. Renshaw ◽  
Dina R. Mody ◽  
Patricia Styer ◽  
Mary Schwartz ◽  
Barbara Ducatman ◽  
...  

Abstract Context.—Previous studies have shown that in gynecologic cytology, cases of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) perform differently on interpretive review. The performance of cases with mixed LSIL and HSIL features is unknown. Objective.—To compare the performance of gynecologic cytology cases of “pure” LSIL and HSIL with cases showing mixed LSIL and HSIL features. Design.—We compiled performance data from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytopathology from the years 2003 and 2004, and compared the performance of slides showing relatively pure LSIL and HSIL (≤10% misclassification as HSIL and LSIL, respectively) with slides showing mixed LSIL or HSIL features (cases misclassified as LSIL or HSIL &gt;10% of the time). Results.—Interpretations from a total of 4508 cases (2452 HSIL and 2056 LSIL) were analyzed. Overall, the sensitivity of participants on slides with a reference diagnosis of HSIL was 97.3%, and of LSIL was 95.9%. Performance trends for pure versus mixed cases varied by slide type and reference diagnosis. For conventional slides, participant sensitivity on pure HSIL cases was greatest (98.0%) and on pure LSIL cases was least (95.2%), while participant performance on cases with mixed features was intermediate (97.0% for mixed HSIL and 96.7% for mixed LSIL). In contrast, participant performance on ThinPrep slides showed the greatest sensitivity for mixed LSIL slides (97.9%), while performance on mixed HSIL slides showed the lowest sensitivity (95.7%); slides with pure features had intermediate sensitivity levels (96.3% for both HSIL and LSIL). Further evaluation demonstrated that conventional pure HSIL slides performed significantly better than mixed HSIL slides (P = .006), whereas mixed LSIL slides performed better than pure LSIL slides (P = .01). For ThinPrep slides, pure HSIL cases performed similarly to mixed HSIL cases (P = .43), while mixed LSIL cases performed better than pure LSIL cases (P = .04). Conclusion.—Slides with mixed LSIL and HSIL features have measurably distinct performance characteristics in comparison to slides with pure LSIL or HSIL features. Participant performance on conventional mixed cases is distinctly different from performance on ThinPrep mixed cases.


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.


2004 ◽  
Vol 2 (6) ◽  
pp. 597-611 ◽  
Author(s):  
J. Thomas Cox

This article reviews the data available as of 2004 on the effectiveness and cost-effectiveness of cervical screening with the two available cytologic methods, the conventional Papanicolaou (Pap; CP) smear and liquid-based cytology (LBC), and discusses the application of LBC to current practice. The majority of LBC studies are on the ThinPrep Pap Test (CYTYC, Boxsborough, MA) and the remainder are on SurePath (TriPath, Burlington, NC), which was previously known as AutoCyte Prep. LBC identified more low-grade squamous intraepithelial lesion (LSIL) Pap test results compared with paired conventional cytology in 17 of 21 ThinPrep and 9 of 12 SurePath “split-sample” studies considered to fulfill the criteria for inclusion in the British NHS Health Technology Assessment (HTA) evaluation of cervical cytology. In four of the six recent ThinPrep and one of two SurePath split-sample studies, more high-grade squamous intraepithelial lesion-positive (HSIL+) results were identified by LBC than by CP. All 15 “direct-to vial studies” meeting HTA criteria reported more LSIL+ results for LBC compared with CP, and all eight of the direct-to-vial studies reporting HSIL+ results separately showed increased detection of high-grade cytology interpretations. Fifteen studies met the criteria for evaluating sensitivity and specificity. Aggregate sensitivity for the CP was 71.5% and for LBC was 80.1%. Indirect comparisons of the two LBC methods did not detect a difference in sensitivity, and a meta-analysis of the six studies comparing specificity between CP and LBC found no difference. Other capabilities of LBC are improved specimen adequacy and the ability to do ancillary testing out of the liquid-based vial. In cost-effective analyses based on models of disease natural history and/or the clinical effectiveness of each screening modality, screening with CP was always dominated by screening with LBC. Primary cervical screening guidelines issued by the American Cancer Society in 2002 recommend repeating the cytology biannually if liquid-based and annually if conventional. The gain in sensitivity, apparent cost-effectiveness, and advantage of having a representative specimen for ancillary testing, support the use of LBC.


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