Treatment of high-grade squamous intraepithelial lesions: a 2- versus 3-step approach

OBJECTIVE: The purpose of this study was to determine whether colposcopically directed biopsy is a necessary step in the evaluation of patients with high-grade squamous intraepithelial lesions. STUDY DESIGN: A retrospective analysis was conducted of the correlation between the high-grade squamous intraepithelial lesion Papanicolaou test and the colposcopically directed biopsy and the correlation between the high-grade squamous intraepithelial lesion Papanicolaou test and the loop electrosurgical excisional procedure. RESULTS: Of 72 patients with high-grade squamous intraepithelial lesions on Papanicolaou test, 48 patients had a pathologic diagnosis on cervical biopsy of CIN II or greater, which provides a 67% correlation between the Papanicolaou test and the colposcopically directed biopsy. Fifty-six patients had a pathologic diagnosis on loop electrosurgical excisional procedure of CIN II or greater, which provides a 78% correlation between the Papanicolaou test and the loop electrosurgical excisional procedure. The median interval between the Papanicolaou test and the definitive treatment was significantly longer (P <.001) when colposcopically directed biopsy was performed before the loop electrosurgical excisional procedure. CONCLUSION: The colposcopically directed loop electrosurgical excisional procedure after a high-grade squamous intraepithelial lesion Papanicolaou test may reduce the time interval between diagnosis and treatment; furthermore, it offers equal correlation when compared with traditional treatment.     

High-grade histologic lesions in women with low-grade squamous intraepithelial lesion cytology from a region of Thailand with a high incidence of cervical cancer

Objective

To evaluate the prevalence of and predictors for underlying significant lesions in women with low-grade squamous intraepithelial lesion (LSIL) smears.

Methods

Records were retrospectively reviewed for 208 women with LSIL who underwent colposcopy and histological evaluation from October 2004 through April 2009.

Results

Mean age of the patients was 38.5 years. Forty-four (21.2%) women were nulliparous; 20 (9.6%) women were postmenopausal; 29 (13.9%) women tested positive for HIV. Thirty-three (15.9%) women were current users of combined oral contraceptive pills. The pathological results of initial colposcopic evaluations were: 63 (30.3%) with cervical intraepithelial neoplasia (CIN) 2-3; 62 (29.8%) with CIN 1; 4 (1.9%) with cervical cancer; and 79 (38.0%) with no epithelial lesion. Current use of combined oral contraceptive pills, a positive HIV test, and multiparity were significant independent predictors for high-grade disease.

Conclusion

Approximately one-third of women with LSIL in our population have underlying significant lesions. Current use of combined oral contraceptive pills, a positive HIV test, and multiparity are significant predictors for high-grade lesions.     

Three-step versus “see-and-treat” approach in women with high-grade squamous intraepithelial lesions in a low-resource country

Objective

To investigate the frequency of cervical intraepithelial neoplasia (CIN) 2 or greater in women with high-grade squamous intraepithelial lesion (HSIL), and to evaluate whether colposcopically-directed biopsy is a necessary procedure for managing HSIL in a low-resource country.

Methods

A retrospective review was undertaken of women with HSIL on a Pap smear.

Results

Of 348 women who had undergone colposcopically-directed biopsies and loop electrosurgical excisional procedure (LEEP), 321 (92.2%) had CIN 2 or greater. Of these, 279 were diagnosed with CIN 2 or greater on biopsy as were 264 on LEEP. The lesions in women who had CIN 2, satisfactory colposcopy, and more biopsies were more likely to be completely excised by biopsy. The mean length of time between the initial Pap smear and LEEP was significantly longer than between the initial Pap smear and biopsy.

Conclusion

Women with HSIL can be effectively managed using the see-and-treat approach in a low-resource country owing to the frequency of CIN 2 or greater.     

Underlying pathology of women with "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" smears, in a region with a high incidence of cervical cancer

AIM: To evaluate the histopathology of women who had "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions" (ASC-H) on cervical cytology in a region with high incidence of cervical cancer. METHODS: This study was conducted at Chiang Mai University Hospital, Chiang Mai, Thailand. All women with ASC-H, who had undergone colposcopic and histolopathologic evaluation between October 2004 and January 2007, were recruited. Similar cohorts with other squamous cell abnormalities on a Pap-smear, who had undergone colposcopy during the same period, were included as comparative groups. RESULTS: During the study period, 85 women who had ASC-H smears underwent colposcopic and histopathologic evaluation. The mean age was 45.3 years (range, 20-64 years). The histopathologic results of these 85 women were as follows: cervical intraepithelial neoplasia (CIN) II-III, 52 (61.2%); invasive cancer, 7 (8.2%); CIN I, 6 (7.1%); and no lesions, 20 (23.5%). The incidence of underlying CIN II or higher in an ASC-H smear (69.4%) was intermediate between atypical squamous cell of undetermined significance (22.7%), low-grade squamous intraepithelial lesion (44.7%) and high-grade squamous intraepithelial lesion (90.5%) smears. There was no statistically significant difference in the incidence of CIN II or higher between women who were 40 years old or more and those who were younger (68.7% and 71.4%, respectively, P=0.81), or between pre-menopausal and post-menopausal women (71.4% and 63.6%, respectively, P=0.49). CONCLUSION: Reporting ASC-H cytology in our population is strongly associated with significant cervical pathology, particularly invasive cancer that is possibly at a rate higher than previously reported. Women who have ASC-H smears should therefore be referred for immediate colposcopy regardless of age and menopausal status.     

Colposcopy audit for improving quality of service in areas with a high incidence of cervical cancer

Objective

To audit routine colposcopy performance using 8 standard requirements of the National Health Service Cervical Screening Programme (NHSCSP).

Methods

Records of women who underwent colposcopy for abnormal cervical cytology between January and December 2008 at Chiang Mai University Hospital, Thailand, were reviewed.

Results

The standard requirements were not achieved in 2 practices: (1) the proportion of women who had recordings of visibility of the transformation zone (96.6%) did not achieve the NHSCSP requirement of 100%; and (2) the rate of excisional biopsy (87.8%) was lower than the 95% minimum required.

Conclusion

Colposcopic performance at Chiang Mai University Hospital was generally favorable. However, re-audit is necessary to ensure that unmet standards of performance are improved and achieved standards are maintained.     

Women in a region with high incidence of cervical cancer warrant immediate colposcopy for low-grade squamous intraepithelial lesion on cervical cytology

The objective of this study was to determine the prevalence of high-grade histologic diagnoses in women who had low-grade squamous intraepithelial lesion (LSIL) on Pap smear in an area with high incidence of cervical cancer. We conducted a retrospective study of 220 women with LSIL cytology undergoing colposcopic examination in Chiang Mai University Hospital between January 1999 and July 2004. The histologic diagnoses, obtained from colposcopically directed biopsy or electrical loop excision after initial colposcopy, showed that 80 (36.4%) women had histologically confirmed high-grade lesions and 11 (5%) women had microinvasive (9) and frankly invasive (2) carcinomas. Overall, 41.5% of women with LSIL on Pap smear had significant underlying lesions, requiring appropriate treatment. In conclusion, in the region with high incidence of cervical cancer, women with LSIL cytology are at increased risk of having underlying high-grade lesions and invasive cancer. Immediate referral for colposcopy is warranted.     

See-and-treat management of high-grade squamous intraepithelial lesions in a resource-constrained African setting

Objective

To compare the treatment outcomes of women with high-grade squamous intraepithelial lesions (HSIL) who underwent immediate loop electrosurgical excision procedure (LEEP) and those who had directed biopsies prior to subsequent LEEP.

Methods

Women who were referred for HSIL to 2 centers in southeast Nigeria were examined via colposcopy. Those with positive colposcopic findings were randomized to receive either immediate LEEP (see-and-treat group) or directed biopsies (3-step group). Women with directed biopsy-confirmed results underwent follow-up LEEP. Overtreatment rate, cost, default rate, and cytology–treatment interval were compared between the 2 groups.

Results

In total, 314 women were included in the study. The overtreatment rate was similar between the groups. Treatment cost and cytology–treatment interval were significantly higher in the 3-step group (P = 0.0001). The default rate was significantly lower in the see-and-treat group (P = 0.0001). Most (219 [69.7%]) participants preferred the see-and-treat approach.

Conclusion

Immediate see-and-treat LEEP for women with HSIL in southeast Nigeria is cheaper, less time-consuming, and associated with better patient compliance than the 3-step management procedure. Furthermore, it does not lead to significantly higher overtreatment. The immediate see-and-treat approach may be ideal for the management of women with HSIL in low-resource countries.     

Human papillomavirus (HPV) type distribution in cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in Venezuelan women

Objective

Cervical cancer is an important cause of mortality among women in developing countries, especially in the Latin America and Caribbean (LAC) region. Infection with high-risk (HR) human papillomavirus (HPV) has been identified as the primary cause of cervical cancer. The aim of this study was to determine the frequency of HR-HPV genotypes in low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical carcinoma (CC) among Venezuelan women.

Materials and methods

Subjects with histopathological diagnosis of LSIL, HSIL, and CC (LSIL = 200; HSIL = 100; CC = 150) were enrolled in the study after obtaining informed consent. Biopsy samples of these subjects were analyzed to determine the lesion type. HPV detection and typing was done using polymerase chain reaction (PCR) and reverse hybridization. HPV type specific prevalence was determined in subjects with single and multiple infections.

Results

HPV DNA was detected in 68%, 95%, and 98.7% of LSIL, HSIL, and CC cases, respectively. HR-HPV and low-risk oncogenic HPV (LR-HPV) was observed in 66.9%/11.8% of LSIL cases, 87.3%/3.2% of HSIL cases, and 91.2%/0.7% of CC cases. HPV types -16/-18 (65%) were the most common high-risk HPV types observed, followed by types -52, -33, -45, and -31.

Conclusion

Cervical cancer burden in Venezuelan women is substantial. HPV types -16/-18 were the most common types prevalent among Venezuelan women followed by types -52, -33, -45, and − 31 (prevalence, ~ 90.1%). The results of this study provide baseline information on the HPV type distribution, which may facilitate the development of a cervical cancer prevention and control program in Venezuela.     

Prevalence and genotype distribution of human papillomavirus in women with cervical cancer or high-grade precancerous lesions in Chengdu, western China

Objective

To study the prevalence and genotype distribution of human papillomavirus (HPV) among women with cervical cancer or high-grade squamous intraepithelial lesions (HSIL) in western China.

Methods

Cervical cast-off cells from 144 women with cervical cancer and 63 women with HSIL were tested for HPV genotypes using an oligonucleotide microarray.

Results

The overall HPV prevalence was 80.6% in cases of carcinoma and 61.9% in cases of HSIL. The most common genotypes were HPV-16 (carcinoma, 68.1%; HSIL, 34.9%) and HPV-58 (carcinoma, 8.3%; HSIL, 17.5%). Other high-risk types included HPV-18, -31, -33, -35, -45, and -52, with HPV-18 more common in adenocarcinomas than in squamous cell carcinomas (21.4% vs 3.1%; P < 0.02). The HPV prevalence was lower among patients older than 49 years (P < 0.02).

Conclusion

The prevalence of HPV-16 and HPV-58 was high. This finding may help to improve HPV vaccination and cervical cancer prevention programs in western China.     

宫颈环形电切术治疗宫颈高级别鳞状上皮内病变的疗效及预后影响

目的 观察宫颈环形电切术（LEEP）治疗宫颈高级别鳞状上皮内病变（HSIL）的疗效及预后影响。方法 选取60例HSIL患者,根据手术方法不同分为LEEP组与冷刀锥切术（CKC）组,每组30例。LEEP组患者实施宫颈环形电切术治疗,CKC组患者实施冷刀锥切术治疗。比较两组围手术期指标、术后人乳头瘤病毒（HPV）转阴率、宫颈成型率及妊娠率。结果 LEEP组患者术中出血量明显少于CKC组,手术时间、住院时间均短于CKC组,差异有统计学意义（P<0.05）;两组宫颈切除面积比较,差异无统计学意义（P>0.05）。LEEP组术后1个月宫颈成型率96.67%明显高于CKC组的76.67%,差异有统计学意义（P<0.05）。随访6～12个月,LEEP组术后HPV转阴率为90.00%,CKC组术后HPV转阴率为93.33%,比较差异无统计学意义（P>0.05）;LEEP组妊娠率56.67%明显高于CKC组的16.67%,差异有统计学意义（P<0.05）。结论 LEEP在HSIL治疗中,可明显减少术中出血量,缩短手术时间及住院时间,提高术后HPV转阴率、宫颈成型率及妊娠率,...     

宫颈高度鳞状上皮内病变治疗后高危型人乳头瘤病毒的消退规律

目的探讨宫颈高度鳞状上皮内病变治疗后高危型人乳头瘤病毒(HPV)的消退规律,了解术后高危型HPV持续感染与病变残留或复发之间的关系。方法对2003年1月至2007年12月在广东省人民医院因宫颈高度鳞状上皮内病变行宫颈电环切除术的502例妇女的随访资料进行回顾性分析。结果术前存在高危型HPV感染的宫颈高度鳞状上皮内病变进行宫颈电环切除术治疗后,术后6、12、18、24个月HPV清除率分别为83.63%、94.39%、97.31%、98.88%。术后高危型HPV持续感染人群病变残留或复发率达26.85%。结论宫颈电环切除术后6个月高危型HPV己大部分消退,术后2年基本完全消退。术后宫危型HPV持续感染是病变残留或复发的高危因素,术后HPV阳性妇女,宜严密随访。     

Cryotherapy for HPV clearance in women with biopsy-confirmed cervical low-grade squamous intraepithelial lesions

Objective

To compare the clearance rate of HPV infection among women aged older than 30 years with biopsy-confirmed cervical low-grade squamous intraepithelial lesions (LSIL) 1 year after cryotherapy with the spontaneous clearance rate (observation).

Method

HPV DNA typing by polymerase chain reaction and reverse line blot hybridization were used to identify 14 high-risk types and 23 low-risk types. HPV DNA sequencing was also used for other types.

Result

Between December 2007 and March 2009, 100 women were recruited to the study and 60 cases had positive results on HPV testing. Twenty-nine patients were randomly allocated to the cryotherapy group and 31 to the observation group. At 1 year, 89.7% (26/29; 95% CI, 78.6-100%) of the cryotherapy group and 90.3% (28/31; 95% CI, 79.9-100%) of the observation group had negative results on HPV testing (0.6% difference; 95% CI, -15.8 to 14.6%, P = 0.94).

Conclusion

Cryotherapy failed to increase the clearance of prevalent HPV infections among women with LSIL, although in both arms the clearance rates were above 80%. However, in coupling with visual inspection with acetic acid as a single visit approach, its effect on prevention of HSIL and cervical cancer is still promising. Therefore, cryotherapy should not be withdrawn from such programs. (ClinicalTrials.gov Identifier: NCT00566579).     

High-risk human papillomavirus,other than type 16/18, in predominantly older Taiwanese women with high-grade cervical preinvasive lesions

ObjectiveTo investigate the various genotypes of human papillomavirus (HPV) in Taiwanese women patients with abnormal cervical cytology and analyze the associations between HPV types, cervical preinvasive lesions, and the medical characteristics of these patients.Materials and MethodsWe performed HPV genotyping GeneChip procedures and colposcopies for 784 women with abnormal Papanicolaou smears. The characteristics of the patients and the status of the HPV infection were correlated.ResultsA total of 706 (90.1%) of the 784 women were positive for HPV infection, including 641 patients with high-risk HPV (HR-HPV). Among the patients with high-grade squamous intraepithelial lesions (HSILs), the average age of the 273 patients with other HR-HPV types (48.6 ± 13.8 years) was significantly older than the 222 patients infected with HPV 16/18 (39.8 ± 11.8 years) (p < 0.001). The proportion of patients with HSILs who were older than 40 years and infected with other HR-HPV types (76.6%) was also significantly higher than those with HPV 16/18 (20.3%) (p < 0.001).ConclusionWomen older than 40 years and having abnormal Pap smears and HR-HPV infections other than type 16/18 should be managed carefully because of the risk for HSILs.     

绝经后子宫颈高级别病变妇女子宫颈锥切术后病理升级为癌的影响因素分析#br#

【Abstract】?Objective?To investigate the related influencing factors of upgraded pathology after cervical conization of high-grade squamous intraepithelial lesions in postmenopausal women. Methods?Clinical data of 424 postmenopausal women with high-grade squamous intraepithelial lesions who underwent cervical conization in the First Affiliated Hospital of Zhengzhou University between June 2017 and November 2018 were retrospectively analyzed. According to whether the pathology was upgraded after conization,they were divided into upgraded group(68 cases)and non-upgraded group (356 cases), and the influencing factors of updated pathology were analyzed. Results?Among the 424 postmenopausal patients, 68 cases(16.0%) had updated pathological result after cervical conization.Univariate analysis showed that HPV16/18 infection, cytology with HSIL, typeⅢtransformion zone(TZ), atypical vessels, visible lesion size, number of biopsy, ECC, glandular involvement and immunosuppression status were significantly related to upgrade pathology after cervical conization (P＜0.05). Multivariate logistic analysis found that HPV16/18 infection, glandular involvement, atypical vessels and visible lesion size were independent risk factors for predicting postoperative updated patholog result (P＜0.05). Conclusion?HPV16/18 infection, glandular involvement, atypical vessels and visible lesion size are independent risk factors for predicting postoperative pathological upgrading in postmenopausal women.Patients with these risk factors should be given high attention.     

高级别宫颈鳞状上皮内病变LEEP术后病理升降级的相关因素分析

目的 探讨宫颈高级别鳞状上皮内病变(HSIL)宫颈环形电切术(LEEP)患者术后病理升降级的相关因素.方法 回顾性分析2019年1月至2020年6月在上海交通大学附属国际和平妇幼保健院就诊的经阴道镜活检组织学诊断为HSIL并接受LEEP手术的449例患者的临床资料,比较各相关因素与术后病理升降级的关系.结果 ①年龄＜4...     

Methylated ZNF582 gene as a marker for triage of women with Pap smear reporting low-grade squamous intraepithelial lesions — A Taiwanese Gynecologic Oncology Group (TGOG) study

Objective

Our previous work revealed that host genes ZNF582, PTPRR, PAX1, and SOX1 are highly methylated in cervical intraepithelial neoplasias grade 3 or worse (CIN3⁺). In this study, we used a standardized testing assay to evaluate the clinical efficacy of these biomarkers in the triage of cytological diagnoses of low-grade squamous intraepithelial lesions (LSILs), and compared the performance with human papillomavirus (HPV) testing.

Methods

This 2-year multicenter prospective study examined a population of 230 women from 12 medical centers who were diagnosed with LSILs on cervical cytology. Cervical scrapings were obtained prior to a colposcopy-directed biopsy for quantitative methylation analysis of ZNF582, PTPRR, PAX1, and SOX1, and HPV testing. Using logistic regression and receiver operating characteristic curve analyses, the abilities of methylated genes and HPV to predict CIN3⁺ were assessed.

Results

Fifteen (6.5%) of the 230 women with a cytological diagnosis of LSIL were confirmed to have CIN3⁺ after a colposcopy-directed biopsy. Among the 4 methylated genes, ZNF582 was found to be the best biomarker for detecting CIN3⁺. The sensitivities for methylated ZNF582 and HPV testing were 73% and 80%, and the specificities were 71% and 28%, respectively. The odds ratio for predicting CIN3⁺ using methylated ZNF582 was 6.8 (95% confidence interval (CI) 2.1–22.1), which was much better than HPV testing (OR = 1.6, 95% CI 0.4–5.8).

Conclusion

This is the first study to show that ZNF582 methylation analysis of cervical swabs may be a promising choice in the positive triage of cytological diagnoses of LSILs.     

Post-coital vaginal douching is risky for non-regression of low-grade squamous intraepithelial lesion of the cervix

Background

Vaginal douching is a common practice worldwide. Its effect on the natural history of the early lesion of human papillomavirus (HPV) infection, low-grade squamous intraepithelial lesion (LSIL), is unknown.

Methods

In a prospective nation-wide cohort (n = 1332), epidemiological variables including habit of vaginal douching after intercourse and outcomes of LSIL were studied. Colposcopy-confirmed LSIL women (n = 295) were followed every 3 months. Parameters of HPV infection, sexual behavior, personal hygiene and environmental exposures were compared with the follow-up outcomes.

Results

There was a 15% chance of HSIL co-existing with the LSIL cytology result. Eight percent of colposcopy-confirmed LSIL were found with HSIL in 1 year. With a follow-up of up to 36 months, 83% LSIL regressed, 11% progressed and 6% persisted. The mean time (95% CIs) to regression and progression were 5.2 (4.7-5.8) and 8.0 (5.8-10.3) months, respectively. Risk factors of the non-regression of LSIL included HPV prevalence on enrollment, habit of vaginal douching after intercourse with a hygiene product and non-regular Pap screening, with odd ratio of 4.4 (1.9-10.3), 3.14 (1.04-9.49) and 2.12 (1.24-3.62), respectively. HPV prevalence and vaginal douching also conferred a slower regression of LSIL (8.0 vs. 4.1 months, P < .001 and 8.0 vs. 5.6 months, P = 0.02, respectively).

Conclusion

The study disclosed a transient but warning nature of cytological LSIL. Practicing of vaginal douching after intercourse, especially with hygiene products, is associated with non-regression of LSIL.