Situation analysis of atypical squamous cells of undetermined significance smears in Songklanagarind Hospital

OBJECTIVE: To review the incidence, management, follow-up rate and colposcopic diagnosis of atypical squamous cells of undetermined significance (ASCUS) detected on cervical smears in Songklanagarind Hospital, Thailand. METHODS: A retrospective study of ASCUS smears taken during January 2000 to March 2001 at Songklanagarind Hospital was performed. The type of management was classified and the follow-up rate was detected. Cases with colposcopy, tissue biopsy, endocervical curettage, conization and hysterectomy specimen were reviewed. In the cases without tissue biopsy, the final diagnoses were based on the colposcopic examination. RESULTS: Among the 25068 Pap smears examined, the incidence of ASCUS was 0.62%. Of these, only 56.13% received the further evaluation. The non-compliance rate was 18.71%. The incidences of cervical intraepithelial neoplasia (CIN) and invasive cancer among the cases who received colposcopy were 15.96% and 2.13%, respectively. The incidence of CIN or invasive cancer in ASCUS favor reactive and ASCUS favor neoplasia were not different statistically significant. CONCLUSIONS: Management of ASCUS smears by follow-up may be inappropriate. A practice guideline which consists of active management, intensive follow-up system and well-organized data management should be used to improve the situation.     

宫颈细胞学检查为ASCUS的临床意义及处理探讨

目的:探讨宫颈细胞学检查为ASCUS(不典型鳞状细胞-意义不明)的临床意义和处理方法。方法:2005年3月至2007年9月,对上海市第十人民医院妇科就诊的218例细胞学检查报告为ASCUS患者行阴道镜评估与镜下活检,其中100例患者同时进行了高危HPV-DNA检测。结果:218例ASCUS患者中宫颈上皮内瘤变(CIN)的发生率为49.54%,高级别CIN及浸润癌的发生率为17.43%,阴道镜拟诊≥CINⅡ40例,与病理结果相符29例,符合率72.5%(29/40)。高危HPV阳性组CIN检出率为66.67%,明显高于阴性组的36.96%。高级别CIN(CINⅡ、CINⅢ)17例中16例高危HPV-DNA检测阳性,仅1例CINⅡ为阴性。鳞癌3例,高危HPV检测均为阳性。结论:细胞学报告为AS-CUS时,阴道镜下病理活检结果相差大,而且可能是发现高度CIN的第一个信号,需引起重视。高危HPV-DNA检测是一种有效的ASCUS分流管理手段,能提高CIN的检出率。     

阴道镜检查在宫颈细胞学ASCUS分流管理中的应用

目的探讨电子阴道镜检查在宫颈细胞学意义未明的不典型鳞状细胞(atypical squamous cell of undeter-mined significance,ASCUS)分流管理中的临床应用价值。方法对2006年7月至2008年7月在天津医科大学第二医院门诊行宫颈液基细胞学检查(TCT)结果为ASCUS的471例患者进行电子阴道镜检查,其中203例阴道镜诊断为宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及以上病变者在可疑病变区取活检送病理检查;268例阴道镜检查为正常或慢性宫颈炎者给予阴道用药治疗1~3个疗程,3个月后复查宫颈涂片,4例细胞学仍异常者行阴道镜下取活检送病理检查,余264例细胞学阴性者定期复查宫颈细胞学。结果471例宫颈细胞学AS-CUS患者中,共行活体组织病理学检查207例(43.95%),检出宫颈上皮内瘤样病变(CINⅠ~Ⅲ)131例,宫颈癌4例,余264例避免了宫颈活检损伤,随访6~30个月复查宫颈细胞学均未发现异常。结论电子阴道镜结合宫颈细胞学检查可有效检出宫颈细胞学ASCUS中CIN及宫颈癌患者,可作为基层医院对ASCUS进行有...     

Role of human papillomavirus DNA testing in management of women with atypical squamous cells of undetermined significance

To find the sensitivity, specificity, and positive and negative predictive values of the high-risk group human papillomavirus (HPV) DNA testing as a triage tool to detect high-grade squamous intraepithelial lesions (HSILs, ie, cervical intraepithelial neoplasia [CIN] 2 or worse) in women with a cytologic smear showing atypical squamous cells of undetermined significance (ASC-US). All new cases with cytologic smears showing ASC-US that presented in King Chulalongkorn Memorial Hospital from January 2003 to November 2003, excluding known cases of HSILs and pregnancies, were enrolled. Cervical cell samplings were done by cervical cytobrush technique and tested for high-risk group HPV with the Hybrid Capture 2 (HC2) test. All participants were examined under a colposcope. Then cervicographs were taken before colposcopic-directed cervical biopsies were done. Of the 90 ASC-US cases enrolled, the pathologic results were normal in 30.0%, squamous metaplasia in 16.7%, CIN 1 in 37.8%, CIN 2 in 1.1%, CIN 3 in 11.1%, and microinvasive cervical carcinoma in 3.3%. The prevalence of HSILs and the prevalence of high-risk HPV detection were 15.6% and 38.9%, respectively. Using pathologic results from cervical biopsy as the gold standard, the HC2 has the sensitivity, specificity, and positive and negative predictive values of 85.7%, 69.7%, 34.3%, and 96.4%, respectively, to detect HSILs. High-risk group HPV detection can be used as an additional triage test to detect HSILs in women having ASC-US with high sensitivity and negative predictive value.     

Risk of precancer and follow-up management strategies for women with human papillomavirus-negative atypical squamous cells of undetermined significance

OBJECTIVE: To investigate the relative performances of follow-up cytology and carcinogenic human papillomavirus (HPV) DNA testing among carcinogenic HPV-negative women with atypical squamous cells of undetermined significance (ASCUS), for detection of cervical precancer. METHODS: Twelve-month follow-up management strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3) or worse using cytology or HPV testing or both were compared among women with HPV-negative ASCUS in the Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesion (ASCUS-LSIL) Triage Study. RESULTS: Overall only 22 of 1,559 (1.4%) HPV-negative ASCUS women developed CIN grade 3 or worse during follow-up compared with 269 of 1,767 (15.2%) HPV-positive ASCUS women (P<.001). Because of the low risk of disease among HPV-negative ASCUS women, only 7 cases of CIN3 were diagnosed between 12 and 24 months of follow-up, limiting power to distinguish meaningful differences in sensitivity among 12-month testing strategies. The specificity of HPV testing (84%) was significantly higher than cytology using an ASCUS threshold (71%) (P<.001). Cotesting with cytology and HPV testing at 12 months resulted in even lower specificity (61%). Because cases were uncommon, the positive predictive value for subsequent CIN3 or worse was low for cytology (2.6%), Hybrid Capture 2 (3.8%), and cotesting with cytology and HPV testing (2.2%). The negative predictive value for all three management strategies was very high (99.70%, 99.82%, and 100.0% for HPV testing, cytology, or cotesting, respectively.) CONCLUSION: Women with HPV-negative ASCUS have very low absolute risk of subsequently detected CIN3 or worse in the subsequent 2 years, similar to women with a negative cytology in the absence of HPV testing. The results suggest that women with HPV-negative ASCUS should return to routine screening intervals which may be longer than 1 year depending on age and screening history. However, if increased surveillance is chosen, a single HPV test for carcinogenic types at 12 months has significantly higher specificity and lower referrals than cytology.     

Colposcopic and histologic findings in women with a cytologic diagnosis of atypical squamous cells of undetermined significance

BACKGROUND: The optimal method for managing a patient diagnosed with atypical squamous cells of undetermined significance (ASCUS) has not yet been established. The interim guidelines published by the National Cancer Institute suggest that a patient should be referred for colposcopy after the second ASCUS diagnosis within 2 years. AIM: To assess the significance of ASCUS in predicting the presence of underlying squamous intraepithelial lesion (SIL) of the uterine cervix. STUDY POPULATION: Women undergoing colposcopy for ASCUS cytology at a teaching hospital in Tehran University, in the years 1998-2001, considered eligible to enter this retrospective study. RESULTS: Of the 266 patients who underwent colposcopy, 28 (11%) had low-grade squamous intraepithelial lesion (LSIL), 16 (6.3%) had high-grade squamous intraepithelial lesion (HSIL) two (0.8%) had squamous cell carcinoma (SCC), and 48 (18.8%) had flat condyloma. CONCLUSION: Atypical squamous cells of undetermined significance (ASCUS) on a cervical smear is a good marker for detecting underlying SIL and condyloma. Thus, immediate colposcopy and directed biopsy are appropriate follow-up procedures.     

Postcolposcopy management strategies for women referred with low-grade squamous intraepithelial lesions or human papillomavirus DNA-positive atypical squamous cells of undetermined significance: a two-year prospective study

OBJECTIVE: This study was undertaken to compare postcolposcopy management strategies for women referred for low-grade squamous intraepithelial lesions (LSIL) or oncogenic human papillomavirus (HPV) DNA-positive atypical squamous cells of undetermined significance (ASCUS), with cervical intraepithelial neoplasia (CIN) grade 1 or less found at initial colposcopy. STUDY DESIGN: A 2-year prospective follow-up of 1539 women was designed to assess the percentage sensitivity of different postcolposcopy management strategies to detect subsequent CIN grade 2 or 3 and percentage referral to repeat colposcopy. RESULTS: HPV testing at 12 months was sensitive (92.2%) for detection of CIN grade 2 or 3 with a referral rate to repeat colposcopy of 55.0%. Repeat semiannual cytology with referral to colposcopy at an ASCUS threshold demonstrated similar sensitivity (88.0%) but with a higher rate of referral to colposcopy (63.6%). Combining cytology and HPV testing did not increase sensitivity and hurt specificity. Baseline viral load and colposcopic impression were not helpful. CONCLUSION: The most efficient test for identifying women with CIN grade 2 or 3 after colposcopy might be an HPV test alone at 12 months.     

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.     

Human papillomavirus prevalence in postradiotherapy uterine cervical carcinoma patients: correlation with recurrence of the disease

To understand the role of human papillomavirus (HPV) in recurrence of uterine cervical cancer (CA-CX) after radiotherapy, we have analyzed the HPV prevalence in the exfoliated cells of 56 patients and their corresponding plasma. HPV DNA was detected in exfoliated cells of 78% (44/56) patients (HPV-16, 68%; HPV-18, 14%; HPV-X [other than 16, 18], 11%; and mixed infection of HPV-16 and HPV-18 in three cases). HPV DNA in plasma was present in only 25% (11/44) of the HPV-positive exfoliated cells (positive predictive value, 100%; negative predictive value, 27%) with concordance in HPV types. The recurrence of the disease was significantly associated with the presence of HPV in the exfoliated cell (P= 0.01) and plasma (P= 0.007) as well as high viral load in the exfoliated cell (P= 0.0002). Kaplan-Meier disease-free estimates have also shown the significant association between HPV prevalence in plasma and recurrence of the disease (P= 0.045). Thus, it indicates that in postradiotherapy CA-CX patients, the high viral load in the exfoliated cell as well as HPV presence in the plasma samples could be used in early detection of the patients at increased risk for disease recurrence and progression.     

2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests

A group of 146 experts representing 29 organizations and professional societies met September 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. Recommendations for managing atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion (LSIL) are essentially unchanged. Changes were made for managing these conditions in adolescents for whom cytological follow-up for 2 years was approved. Recommendations for managing high-grade squamous intraepithelial lesion (HSIL) and atypical glandular cells (AGC) also underwent only minor modifications. More emphasis is placed on immediate screen-and-treat approaches for HSIL. Human papillomavirus (HPV) testing is incorporated into the management of AGC after their initial evaluation with colposcopy and endometrial sampling. The 2004 Interim Guidance for HPV testing as an adjunct to cervical cytology for screening in women 30 years of age and older was formally adopted with only very minor modifications.     

Cervical cytology of atypical squamous cells, cannot exclude high-grade squamous intra-epithelial lesion: significance of age, human papillomavirus DNA detection and previous abnormal cytology on follow-up outcomes

Objective

Despite the usefulness of Pap tests for cancer screening, outcomes can be difficult to predict when atypical squamous cells (ASCs) are identified. According to the 2001 Bethesda system, ASCs can be subdivided into two groups: ASCs of undetermined significance (ASC-US); and ASCs, cannot exclude high-grade squamous intra-epithelial lesion (ASC-H). ASC-H interpretations are uncommon, and studies involving this type of lesion are based on small numbers of cases.

Study design

Cross-sectional, retrospective study of 392 ASC-H cases. The follow-up outcomes of ASC-H cases that were diagnosed during routine primary screening between 2002 and 2008 were investigated, and relationships between clinicopathological parameters were assessed, particularly positive test for high-risk HPV (HPV) DNA, patient age at diagnosis and previous abnormal cytology.

Results

Of the 392 cases, high-grade squamous intra-epithelial lesion (HSIL) was detected in 111 (28.3%) cases, squamous cell carcinoma was detected in 15 (3.8%) cases, low-grade squamous intra-epithelial lesion was detected in 37 (9.4%) cases, reactive change was detected in 178 (45.4%) cases, atrophy was detected in 47 (12.0%) cases, and adenocarcinoma was detected in four (1.0%) cases. The prevalence of HSIL or greater was 27.8% for women aged ≥40 years, and 52.3% for women aged <40 years (p < 0.001). HPV positivity in ASC-H smears was significantly associated with HSIL or greater, irrespective of age (<40 years, p = 0.003; ≥40 years, p < 0.001). ASC-H with previous abnormal cytology greater than ASC-US showed a significantly higher detection rate for HSIL or greater at follow-up (p < 0.001).

Conclusions

Patient age, positive HPV DNA test and previous abnormal cytology are useful predictors of underlying HSIL or greater in women with ASC-H.     

早期宫颈癌保留生育功能治疗后肿瘤和妊娠结局的多中心研究

目的探讨宫颈癌保留生育功能治疗后肿瘤和妊娠结局对临床的指导价值。方法选取北京市9个研究中心2008年1月至2012年5月55例保留生育功能治疗的宫颈癌患者为研究对象,收集临床资料及随访结果,对数据进行统计学分析。结果 55例中子宫颈鳞癌52例,子宫颈腺癌3例;FIGO（2009）分期ⅠA1期17例,ⅠA2期7例,ⅠB1期31例;48例行广泛宫颈切除＋腹膜后淋巴结切除术,7例行次广泛宫颈切除＋腹膜后淋巴结切除术;11例术前行新辅助化疗1～2疗程,9例术后进行1～6个疗程的化疗。术后完成随访53例（96.4%）,中位随访时间19.2个月,49例（92.5%）对目前生活质量满意。肿瘤结局和妊娠结局如下：①保留生育功能治疗后肿瘤复发1例（1.9%）;②治疗后有妊娠计划的26例患者中,9例（9/26,34.6%）共有11次妊娠;其中足月分娩6次（6/11,54.5%）,早产2次（2/11,18.2%）,自然流产（10周）、人工流产（8周）及药物流产（6周）各1次（1/11,9.1%）。结论广泛/次广泛宫颈切除术作为年轻早期宫颈癌患者保留生育功能的治疗方法,安全有效,妊娠结局良好。     

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study

Objective

To define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in women with newly diagnosed Stages II-IV ovarian, fallopian tube, or primary peritoneal carcinoma.

Methods

Patients received escalating doses of paclitaxel IV and carboplatin IP on day 1 and paclitaxel IP 60 mg/m² on day 8. A standard 3 + 3 design was used in the escalation phase. A two-stage group sequential design with 20 patients at the MTD was used in the feasibility phase. Patient-reported neurotoxicity was assessed pre and post treatment.

Results

Patients were treated with paclitaxel 175 mg/m² IV and carboplatin IP from AUC 5-7 on day 1 and paclitaxel 60 mg/m² IP on day 8. The MTD was estimated at carboplatin AUC 6 IP and 25 patients enrolled at this dose level. Within the first 4 cycles, seven (35%) of twenty evaluable patients had dose-limiting toxicities (DLTs) including grade 4 thrombocytopenia (1), grade 3 neutropenic fever (3), > 2 week delay due to ANC recovery (1), grade 3 LFT (1), and grade 3 infection (1). De-escalation to paclitaxel 135 mg/m² IV was given to improve the safety. After six evaluable patients completed 4 cycles without a DLT, bevacizumab was added and six evaluable patients completed 4 cycles with one DLT (grade 3 hyponatremia).

Conclusions

Paclitaxel at 175 mg/m² IV, carboplatin AUC 6 IP day 1 and paclitaxel 60 mg/m² IP day 8 yield 18-56% patients with DLTs. The tolerability of the regimen in combination with bevacizumab was indicated in a small cohort.