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.     

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.     

Persistent papillomavirus type-31 and type-45 infections predict the progression to squamous intraepithelial lesion

ObjectiveHuman papillomavirus (HPV) has been recognized as the major etiologic agent of cervical squamous cell carcinoma. However, it has been demonstrated that HPV infection is usually a self-limited process and does not lead to significant epithelial lesions or cancer. Recent data indicate that persistent high-risk HPV (HR-HPV) infections have a significantly increased risk of developing incident high-grade cervical intraepithelial neoplasia and cervical cancer. Our aim, therefore, was to assess whether there exist HPV genotypes whose persistence can be considered powerful surrogates of a progressive disease. We retrospectively selected all patients with a negative cytological diagnosis or with atypical squamous cells of undetermined significance, with a positive test for HR-HPV, different from HPV types 16 and 18, and assessed the significance of the risk of progression based on the persistence of the specific HR-HPV.Materials and methodsWe retrospectively queried the database of our Colposcopy Clinic for all patients with a negative cytological diagnosis or with atypical squamous cells of undetermined significance and a positive test for HR-HPV, and we calculated the incidence of progression to lesions greater than or equal to low-grade squamous intraepithelial lesions after 6 months, according to the HPV type.ResultsA progression rate of 48.27% was found in patients tested positive for HPV-31 (Group 1), 38.46% in patients tested positive for HPV-45 (Group 2), and 5.73% in patients tested positive for HPV types other than HPV-16, HPV-18, HPV-31, and HPV-45 (Group 3).ConclusionOur data demonstrate that the persistence of HPV-31 and HPV-45 is strongly associated with the occurrence of squamous intraepithelial lesion.     

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.     

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).     

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.     

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。     

Upper vaginectomy for the treatment of vaginal intraepithelial neoplasia

OBJECTIVE: The purpose of this study was to evaluate the use of upper vaginectomy for the treatment of vaginal intraepithelial neoplasia (VAIN). STUDY DESIGN: We conducted a retrospective review. Between August 1, 1985 and April 30, 2004, 105 patients were identified who had undergone upper vaginectomy for VAIN. RESULTS: Thirty-six patients had previously been treated for VAIN. Mean operative time and estimated blood loss were 55 minutes and 113 mL, respectively. Ten percent had intraoperative complications. Twenty-three (22%) patients had negative findings on final pathologic examination, and invasive cancer was found in 13 (12%) patients. Four patients had postoperative complications. Follow-up was available in 52 patients; 46 (88%) remain without recurrence at a mean follow-up of 25 months. CONCLUSION: In our patients, upper vaginectomy was efficacious for the treatment of VAIN. The procedure led to the diagnosis of occult invasive cancer in 12% of these women.     

Cervicovaginal secretions protect from human papillomavirus infection: Effects of vaginal douching

ObjectiveCervicovaginal secretions (CVSs) are reported to protect against human papillomavirus (HPV) infection. Although vaginal douching is known to clear both viral inoculants and CVSs, its effect on CVSs in women with HPV infection is unknown.Materials and MethodsThe in vitro HPV pseudovirus infection system was used to test the protective activity of CVSs against HPV infection in samples collected before and after vaginal douching. To simulate different time points of vaginal douching in relation to viral exposure, the cell CVS reconstitute was washed after different viral exposure durations.ResultsIn the CVSs of premenopausal and postmenopausal women who did not perform douching, the CVSs inhibited HPV infection by 56.7 ± 1.8% and 53.6 ± 2.5%, respectively; in women who had performed douching, the CVSs inhibited HPV infection by only 31.2 ± 7.1%, which was significantly lower (p < 0.01). Cell washing effectively cleared 60–90% of the infectious load with the greatest activity occurring within 30 minutes after inoculation. In the presence of CVSs, a sustained inhibition of HPV infection existed for up to 8 hours after HPV exposure, and cell washing increased the clearance to up to 82–93% of the infectious load.ConclusionThis study confirms the protective activity of CVSs against HPV infection regardless of age. In this in vitro study, the net effect of douching was found to be beneficial.     

Human papillomavirus infection in couples with female low-grade intraepithelial cervical lesion

Low-grade squamous intraepithelial lesions (LSIL) are frequently found during cervical cancer screening. Usually they are associated with a human papillomavirus (HPV) infection. Does the high-transmission rate of HPV infection to the male partner represent a clinical risk for him? Are preventive measures to be taken to prevent the occurrence of male diseases?More than 80% of all LSIL are associated with HPV infections. The prevalence of HPV infection in males can range up to 40%, with 60% of the male partners of LSIL female patients presenting with penile flat lesions. The spontaneous cure rate for male infections is very high (90% at 5 years) but negative consequences in females (cervical high-grade lesion and cervical cancer) are frequent. Their male counterparts are far rarer but in some patients can require deleterious treatment. Transmission prevention by the use of condoms and circumcision is discussed. The effectiveness of HPV vaccination in this situation has not been validated.     

Ultrasonic surgical aspiration for vaginal intraepithelial neoplasia

Objective

To determine the safety and efficacy of ultrasonic surgical aspiration (USA) in the treatment of vaginal intraepithelial neoplasia (VAIN).

Methods

Using the ICD code for VAIN, all patients who underwent USA were evaluated. Patient demographics, clinicopathologic data, and follow-up outcomes were abstracted from the medical records.

Results

Ninety-two patients underwent USA for VAIN. No surgical complications or postoperative scarring were recorded, and all patients were followed without further therapy after the procedure. Pathologic evaluation of the degree of VAIN in the aspirate obtained at the time of USA correlated with the preoperative biopsy results in all cases. With a median follow-up period of 4.5 years, the overall recurrence rate was 19.6%. The recurrence rate for high grade VAIN was significantly greater than that for low grade VAIN (32.3% vs 13.1%, P = 0.044).

Conclusion

Ultrasonic surgical aspiration is a safe and effective surgical option for VAIN, providing a histologic sample with minimal invasiveness.     

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.     

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.     

2341例妊娠妇女宫颈筛查及产后随访

目的:分析孕期妇女宫颈细胞学检查、HPV检测、活检组织病理结果及产后自然转归状况。方法:选择2009年1月～2010年2月在北京大学人民医院接受孕期产检及分娩病例,孕前半年未行液基细胞学(TCT)检测,孕早期或中期均进行TCT检查,结果异常者部分行人乳头瘤病毒杂交捕获Ⅱ代(HPVHC-Ⅱ)法检测,阴道镜检查及病理学检查。结果:(1)2341例孕妇中宫颈细胞学意义不明的非典型鳞状上皮细胞(ASCUS)及以上患者60例(2.56%),其中高度鳞状上皮内病变(HSIL)8例(0.34%),低度鳞状上皮内病变(LSIL)4例(0.17%),ASCUS48例(2.05%);细胞学异常者中25例行HPV检测,阳性18例(72%);细胞学异常者28例接受阴道镜检查,病理活检者21例;病理学结果宫颈上皮内瘤变(CIN)共13例(0.56%):CINⅠ3例(0.13%);CINⅡ2例(0.085%),CINⅢ8例(0.34%);(2)产后随访了51例,细胞学正常/炎症41例(细胞学转阴率80.4%),ASCUS8例,LSIL1例,ASC-H1例。孕期HPV阳性者,13例产后复查,4例仍为阳性,孕期与产后比较有显著性差异(P=0.004)。孕期CIN11例中,产后仍为CIN6例(CINⅠ1例、CINⅡ1例、CINⅢ4例),无早期浸润癌发生。结论:(1)妊娠期宫颈细胞学异常在产后有较高的转阴率,同时妊娠期存在较高的HPV亚临床感染,产后转阴率高;(2)妊娠期CIN患者在密切随访下继续妊娠是安全的;(3)妊娠期CIN患者产后应密切随访,若产后仍为CIN应尽快治疗。     

阴道上皮内瘤变28例临床分析

目的: 探讨阴道上皮内瘤变(VAIN)的临床特点、危险因素、诊治及预后。方法: 回顾性分析北京协和医院2005-2011年住院收治VAIN病例28例临床资料。其中VAINⅡ7例,VAINⅢ21例。结果: 患者年龄29～76岁(中位年龄48岁)。绝经21例(75%)。26例(93%)无临床症状。25例(89%)病变位于阴道顶端。27例进行超薄液基细胞学涂片(TCT)检查异常。23例人乳头瘤病毒(HPV)检测阳性。15例有子宫切除术史,其中因宫颈上皮内瘤变(CIN)和宫颈癌切除子宫10例。子宫切除术后至诊断VAIN时间：宫颈疾病平均3.1年,非宫颈疾病8.8年。不同级别VAIN在年龄、子宫切除原因、目前及既往合并宫颈疾病、TCT结果差异无统计学意义。28例全部进行手术治疗,3例术后复发。结论: HPV病毒感染、宫颈病变、宫颈病变或宫颈癌行子宫切除术史是VAIN的危险因素;细胞学-阴道镜-组织病理学适用于VAIN的诊断及随诊;宫颈病变切除子宫治疗后应密切随访,尤其是术后3年内应警惕VAIN。　　     

Laser-skinning colpectomy for extended vaginal intraepithelial neoplasia and microinvasive cancer

Objective

The aim of this study is to analyze the efficacy of colposcopic-guided laser-skinning colpectomy to treat extended high-grade vaginal intraepithelial neoplasia (VaIN).

Methods

Retrospective review of 33 heavily pretreated patients with high-grade VaIN extending over 20–100% of the vaginal surface treated between 2003 and 2013 with colposcopic-guided laser-skinning colpectomy. The vaginal epithelium including all VaIN lesions was excised in one piece with a depth of 2–3 mm.

Results

Vaginal cancer was diagnosed in 10 patients (nine microinvasive squamous cell carcinoma and one vaginal carcinoma). No serious adverse events related to laser-skinning colpectomy were observed. Of 33 patients, 23 were followed up with cytology and colposcopy for at least 12 months at our institution (median follow 26.5 months; range 12–104 months), while five had a shorter follow-up, four an external follow-up and one patient was lost. Of 23 patients with follow-up ≥ 12 months, 20 were disease free after a single laser-skinning colpectomy (overall cure rate 87.0%). Moderate shortening of the vagina was observed in two patients and another two required reconstruction of vaginal strictures during long-term follow-up.

Conclusion

Laser-skinning colpectomy appears to be a feasible treatment for extended high-risk VaIN3. The procedure avoids the mutilation associated with colpectomy and allows early diagnosis and staging of invasive disease.     

Viral load of high-risk human papillomavirus in cervical squamous intraepithelial lesions.

OBJECTIVES: This case-control study was conducted to investigate the role of viral load of high-risk human papillomaviruses (HPVs) in the development of cervical squamous intraepithelial lesions (SILs) and invasive cancers. METHODS: A total of 30 female cases who had histological evidence of low-grade SIL (n=10) or high-grade SIL and above (n=20) were identified as the case group at the Tri-Service General Hospital, Taipei between September 1998 and March 1999. In addition, 80 female controls who had normal cervical cytology were enrolled and individually matched on age (+/-5 years) and date of recruitment to each case. Cervical swabs collected from study subjects were tested for the positivity and viral load of high-risk HPVs by Hybrid Capture II assay. Additionally, subjects completed a risk factor questionnaire. RESULTS: Among sex behavioral factors studied, younger age at first intercourse was associated with a significantly elevated risk of cervical SIL and invasive cancers. With respect to HPV infection, high-risk HPV DNA was present in 70% (21/30) of case and 21% (17/80) of control subjects, resulting in an odds ratio (OR) of 6.6 [95% confidence interval (C.I.)=2.6-17.0]. Moreover, women who had a high viral load were at significantly greater risk for cervical SIL and invasive cancers than those who were infected with a low viral load (OR=18.0, 95% C.I.=3.0-108.5). CONCLUSIONS: Among the variables tested, infection with a high viral load of high-risk HPVs is the strongest determinant for cervical SIL and cervical cancers in Taiwan.