How can the overtreatment rate of "see and treat" approach be reduced in women with high-grade squamous intraepithelial lesion on cervical cytology?

Background: The aim of this study was to determine the incidence and predictors of overtreatment in "see and treat" approach using loop electrosurgical excision procedure (LEEP) in women with high-grade squamous intraepithelial lesion (HSIL) on cervical cytology. The overtreatment was considered when LEEP specimens contained no cervical pathology. Between January 2001 and April 2006, 446 women with HSIL on Pap smear underwent colposcopy followed by LEEP at Chiang Mai University Hospital. Mean age of these patients was 45.6 years with a range of 25-78 years. One hundred and twenty-one (27.1%) women were menopausal. Unsatisfactory colposcopy was observed in 357 (80.0%) women. Of 446 women, histologically-confirmed HSIL, invasive cancer, low-grade squamous intraepithelial lesions, and adenocarcinoma in situ were detected in 330 (74.0%), 76 (17.0%), 9 (2.0%), and 5 (1.1%), respectively. The overtreatment rate on LEEP specimens was noted in 26 women or 5.8% (95% confidence interval [CI] = 3.8 to 8.4) of 446 women. By multivariate analysis, postmenopausal status was the only significant independent predictor of overtreatment with an adjusted odds ratio of 2.89 (95% CI = 1.30 to 6.43, P = 0.009). When postmenopausal women were excluded from analysis, the overtreatment rate was reduced to only 4.0%. In conclusion, "see and treat" approach appears to be an appropriate strategy in managing women with HSIL cytology. The overtreatment rate could be reduced when such policy is limited for premenopausal women.     

Is the Loop Electrosurgical Excision Procedure Necessary for Minor Cervical Cytological Abnormalities?

Background: To investigate the indications of loop electrosurgical excision procedure (LEEP) and itsovertreatment rates for the see and treat and three step strategies in cases of atypical squamous cells ofundetermined cytology (ASC-US) and low grade intraepithelial neoplasia (LGSIL) cytology. Materials andMethods: We retrospectively analyzed colposcopy directed biopsy (CDB) and LEEP results of 176 paients withASC-US or LGSIL cytologies who underwent colposcopic examination. Results: Initial cytologies were ASCUSin 120 women and LGSIL in 56. According to the see and treat approach immediate LEEP was performed for38women. Among the remaining 138 women, LEEP was performed for 32 whose CDB results revealed CIN2/3lesions. In the see and treat group the recognition of CIN2/3 was found to be 39.4%. The overtreatment rate was60% as compared to 25% in the three step group. In CDB group detection of CIN 2 or greater lesions increasedwith 3 or more biopsies. Conclusions: In patients with ASC-US/LGSIL cytologies CDB should be performedbefore LEEP to prevent overtreatment, with attention to all suspected areas and more than 2 biopsies taken.     

The accuracy of cervical cancer and cervical intraepithelial neoplasia diagnosis with loop electrosurgical excisional procedure under colposcopic vision

Objective

The colposcopic vision guided loop electrosurgical excisional procedure (LEEP) was studied for the effective diagnosis of cervical cancer and cervical intraepithelial neoplasia (CIN).

Methods

A total of 199 patients participated in this study. Individual cases were from gynecologic outpatients at Thammasat University Hospital, Thailand. These had diagnoses for CIN and were selected for treatment with colposcopic guided LEEP. The average age of patients in this study was 45. Menopausal women represented 31%, (61/199) of the patients. The most frequently found Pap smear result among these women (44%, 88/199), was that of high-grade squamous intraepithelial lesion. The next most frequent Pap smear result (32%, 64/199) was low-grade squamous intraepithelial lesion. Patients'' medical records and outcomes were evaluated for consistency of pathological examination between colposcopic directed biopsy and LEEP. Discrepancies between initial diagnosis and the final diagnosis were also analyzed.

Results

The colposcopic guided LEEP accurately determined 100% of the cervical cancer cases and 84.8 % of the high-grade squamous intraepithelial lesion cases. Involvement of the ectocervical or endocervical margin regions was found to be 5% and 10% respectively, in this study. Excessive bleeding complication, either during the excision and/or postoperative recovery was found in 3% and 6% of cases, respectively.

Conclusion

LEEP under colposcopic vision is a recommended technique for ambulatory management of precancerous lesion and early diagnosis of cervical cancer. This technique significantly reduces rate of positive ectocervical cone margin involvement.     

Incidences of Cervical Intraepithelial Neoplasia 2-3 or Cancer Pathologic Diagnoses in Patients with a High Grade Squamous Intraepithelial Lesion Pap Smear Attending a Colposcopy Clinic at Srinagarind Hospital

The aim of this study was to evaluate the outcomes of women with high-grade squamous intraepitheliallesion (HSIL) smears who had undergone the “see and treat” approach compared to those who underwent aconventional approach. The records of women with HSIL smears undergoing colposcopy at Srinagarind Hospitalwere reviewed. In those undergoing the conventional approach, the final histological diagnosis was made on themost severe histological results obtained after initial colposcopy. In the “see and treat” group, the final histologicaldiagnosis was made on the examination of LEEP specimens obtained after initial colposcopy. Overtreatment inthe see and treat group was defined as the LEEP specimens containing cervical intraepithelial neoplasia (CIN) 1or less. During the study period, 302 women with HSIL underwent colposcopy. Twenty (6.6%) were nulliparous.One hundred and ninety-four (64.2%) underwent conventional management while the remaining 108 (35.8%)received the see and treat management. The prevalence of underlying high-grade lesions in women undergoingthe conventional approach was significantly higher than that observed among women undergoing the see andtreat approach (89.2% and 47.2%, respectively, P<0.001). The overtreatment rate in the see and treat group was52.8%. Multivariate analysis revealed that only parity status was a statistically significant factor for predictingthe overtreatment after undergoing the see and treat approach. In conclusion, the overtreatment rate amongwomen undergoing see and treat in this study is notably high and therefore this approach should not be routinelypracticed.     

Cytohistologic Discrepancy of High-Grade Squamous Intraepithelial Lesions in Papanicolaou Smears

Objectives: To evaluate the frequency of cytohistologic discrepancy of high-grade squamous intraepitheliallesions (HSILs) in Pap smears and associated factors. Methods: Medical records of 223 women with HSIL Papsmears who were treated at Thammasat University Hospital were reviewed. Data on age, parity, menopausalstatus, contraceptive use and colposcopic directed biopsy and loop electrosurgical excision procedure (LEEP)pathology results were recorded. Results: Mean (SD) age of patients was 38.0 (9.4) years. The majority werepremenopausal (86.5%) and multiparous (83.9%). Cytohistologic discrepancy between the Pap test andcolposcopic-directed biopsy histology was 45.7% and that between the Pap test and LEEP histology was 29.5%.Fifty-four (24.2%) women had no high-grade CIN on both colposcopic directed biopsy and LEEP. Nulliparity,postmenopausal status and having no oral contraceptive pills use were factors associated with cytohistologicdiscrepancy. Conclusion: The exact cytohistologic discrepancy rate was relatively high (24.2%). Factors associatedwith cytohistologic discrepancy were nulliparity and postmenopausal status and having no oral contraceptivepill use.     

See-and-Treat Approach to Cervical Intraepithelial Lesions in HRH Princess Maha Chakri Sirindhorn Medical Center

Background: To evaluate the overtreatment rate with the see and treat approach in the management of womenwith abnormal cervical cytology. Materials and Methods: A retrospective review of patients with abnormalcervical cytology who underwent S&T at MSMC between January 2008 and December 2012 was conducted.Loop electrosurgical excision procedure (LEEP), histological results, cytology and colposcopic impression wereanalyzed to evaluate overtreatment rate, cyto-histologic correlation and related factors. Results: Average age ofS&T cases was 42 years. Ninety seven percents were referred from affiliated health care providers. The studyrevealed 83.2% patients had HSIL or higher from cervical cytology. Correlation between HSIL and final histologywas relatively low at 75% compared to other studies. Overtreatment rate was 28%. Conclusions: S&T was donein 197 patients in a tertiary care health facility with patient satisfaction. Overtreatment occurred, but the ratecan be reduced with appropriate recommendations. HSIL Pap smears should be reexamined before S&T whilelow grade and lesser colposcopic impression groups should obtain conventional colposcopic approach for patientfuture reproductive benefit.     

Recurrent Rates with Cervical Intraepithelial Neoplasia having a Negative Surgical Margin after the Loop Electrosurgical Excision Procedure in Thailand

LEEP conization has become the treatment of choice in patients presenting with high grade intraepitheliallesions (HSILs) especially in cases with negative surgical margins. However, surveillance after such treatmentis necessary due to the potential for recurrence. To evaluate the recurrent rate in patients with negative surgicalmargins after HSIL treatment with LEEP, the medical records of such patients treated between January 2000and June 2007 were reviewed. All of them subsequently underwent Pap smears every 4-6 months to detect therecurrence of cervical intraepithelial neoplasia. There were 272 patients in the study period. Of these, 9 (3.3%)developed abnormal Pap smears with a median follow up of 12 months. The abnormal smears featured: atypicalsquamous cells of undetermined significance in 5 cases; atypical squamous cells where high grade squamouscell intraepithelial lesion cannot be excluded in 2 cases; and low grade squamous intraepithelial lesions in the 2remaining cases. Further investigation with colposcopic directed biopsies were conducted in all who exhibitedan abnormal Pap smear and only 3 of them (1.1%) showed cervical dysplasia at biopsy. In conclusion, thepatients with HSIL who were treated with LEEP and have negative surgical margins have a very low recurrencerate.     

Treatment of the patients with abnormal cervical cytology: a "see-and-treat" versus three-step strategy

Objective

To examine the correlation between cervical cytology and final histological results in patients who have undergone loop electrosurgical excision procedure (LEEP) with or without colposcopy-directed biopsy.

Methods

A retrospective review was performed of 829 patients who underwent LEEP for abnormal cervical cytology at Gangnam Severance Hospital between January 2004 and December 2008. Patients were classified to three groups according to cervical cytology and also divided into two groups based on the treatment they received: see-and-treat group and the standard three-step group. Final histological results were compared for the each study group.

Results

There were no differences in the final histological results between see-and-treat and three-step group in patients with high-grade squamous intraepithelial lesions (HSIL) cytology (N=523) (p=0.71). However, in patients with low-grade squamous intraepithelial lesions (LSIL)/atypical squamous cells of undetermined significance (ASCUS) (N=257) or normal cytology (N=49), the final histological results were significantly different between see-and-treat and three-step group (p<0.001) and the rate of overtreatment was significantly higher in the see-and-treat group (p<0.001).

Conclusion

A see-and-treat protocol may be a viable alternative only in patients with HSIL cytology if colposcopic impression is suggestive of cervical intraepithelial neoplasia (CIN) 2 or 3 lesions.     

Is the Correlation between Papanicolaou Smear and Histopathology Results Affected by Time to Colposcopy?

Background: Time to colposcopy (TC) after abnormal Pap smears was evaluated for influence on cytohistologiccorrelation (CHC). Materials and Methods: This retrospective study assessed the correlation between TC andCHC of women who had abnormal Pap smears. Colposcopic chart review included participants from 2010-2013 who attended a colposcopic clinic, Thammasat University Hospital, Thailand. Results: Four hundred andsixty cases who had abnormal Pap smears were recruited. Pap reports were atypical smears with low gradesquamous intraepithelial lesion (SIL), high grade SIL and cancer at 339, 114 and 7 cases, respectively. Onehundred and twenty four patients underwent loop electrosurgical excision procedure (LEEP). A half of the caseswere colposcopically examined within 1-2 months after abnormal Pap collection. CHC was 88 percent and notaffected at all by TC. Subjects who attended cervical cancer screening from affiliated health providers had shorterTC than those screened in our tertiary hospital. Conclusions: Time to colposcopy with abnormal Pap smearsconducted at Thammasat University Hospital had a highest frequency of 42 days, in line with the literature.Length of TC does not affect the correlation between Pap and histopathologic reports. A longer waiting periodfor colposcopy did not alter progression or regression of the disease.     

Validity of sampling error as a cause of noncorrelation

BACKGROUND: Sampling error is a common explanation of noncorrelation in women whose Papanicolaou (Pap) tests show high-grade intraepithelial lesions (HSIL) but whose follow-up cervical biopsies show only cervical intraepithelial neoplasia (CIN) 1, koilocytosis, or reactive/inflammatory changes. The purpose of this study was to demonstrate the validity of sampling error in this setting by determining the proportion of negative colposcopic cervical biopsies in women with HSIL who subsequently undergo cone/loop electrode excision procedure (LEEP) biopsies or repeat cervical biopsies that confirm the diagnosis of high-grade CIN (HGCIN). METHODS: In all, 368 cases of HSIL were retrieved from the computerized database from January 1, 2003 to December 31, 2005. Follow-up was obtained as part of routine quality assurance/quality control activities including cytologic-histologic correlation. RESULTS: A total of 368 HSIL Pap diagnoses were retrieved. Of the 254 cases that were followed up by cervical biopsy, 146 showed HGCIN in the biopsy. Of the remaining 108 patients whose cervical biopsies failed to demonstrate HGCIN, 47 had a subsequent procedure, either cone/LEEP, cervical biopsy, or repeat Pap test. Cone biopsy/LEEP was performed in 34 cases (72.3%) with a diagnosis of HGCIN in 19. Repeat cervical biopsy was performed in 9 cases (19.1%) with HGCIN diagnosed in 5. Repeat Pap test was performed in 4 cases (8.5%) with HSIL diagnosed in 2. CONCLUSIONS: In the population of women with HSIL by Pap test followed up by cervical biopsy with or without subsequent cone/LEEP, there was a discordant cervical biopsy rate for HGCIN of 43%. In the subgroup of women with HSIL by Pap test followed up by cervical biopsy and subsequent cone/LEEP or repeat cervical biopsy, the proportion of women with negative colposcopic cervical biopsy and subsequent histology-proven HGCIN was 56%. These figures justify sampling error as a valid cause of noncorrelation in women with HSIL followed up by cervical biopsy alone.     

Should women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, receive reflex human papillomavirus-DNA testing?

BACKGROUND: The 2001 American Society for Colposcopy and Cervical Pathology Consensus Guidelines recommend that women who have Papanicolaou (Pap) smears diagnosed as atypical squamous cells (ASC), cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H) should be referred for immediate colposcopic examination. The objective of this pilot study was to evaluate whether reflex human papillomavirus (HPV)-DNA testing performed on smears diagnosed as ASC-H may obviate the need for immediate colposcopic examination. METHODS: All ThinPrep Pap smears that were diagnosed as ASC-H or atypical squamous metaplastic cells (ASMT) between 2001-2003 and that had HPV-DNA testing and subsequent histologic and/or cytologic follow-up were evaluated. Those smears that were diagnosed as ASMT were reviewed and reclassified under the 2001 Bethesda System as either ASC of undetermined significance (ASCUS) or ASC-H. Smears that were diagnosed as ASCUS were excluded from the study. RESULTS: The study included of 48 smears that were diagnosed as ASC-H. All patients with biopsy-proven HSIL had positive high-risk (HR)-HPV results (100% negative predictive value). Approximately 80% of patients with ASC-H who had biopsy-proven, low-grade intraepithelial lesion on follow-up had positive HR-HPV results. Among the patients who had ASC-H with negative follow-up, 50% had positive HR-HPV results, and 50% had negative HR-HPV results. CONCLUSIONS: Among patients with ASC-H, a negative HR-HPV result was found to be an excellent predictor of the absence of HSIL. The results of this pilot study suggested that HPV-DNA testing may serve as a means to better select which patients with ASC-H on Pap smear should undergo colposcopic examination. This approach potentially may reduce medical costs and eliminate the need for routine colposcopic examination among patients with ASC-H Pap smears.     

Factors predicting occult invasive carcinoma in women undergoing a 'see and treat' approach

This study was undertaken to evaluate the incidence and independent predictors of unexpected invasive cancer of cervix in women with high-grade squamous intraepithelial lesions (HSIL) on Pap smear who had undergone a 'see and treat' approach. Women with HSIL on cervical cytology undergoing colposcopy, followed by loop electrosurgical excision procedure (LEEP) at Chiang Mai University Hospital between January 2001 and April 2006 were analyzed. During the study period, 446 women were identified. Mean age was 45.6 years (range, 25-75 years). One hundred and twenty-one (27.1%) women were postmenopausal. Unsatisfactory colposcopy was observed in 357 (80.0%) women. Of the 446 women, 76 (17.04%, 95% CI= 13.67 to 20.86) had invasive lesions on LEEP specimens. Multivariate analysis revealed that unsatisfactory colposcopy and premenopausal status were statistically significant independent predictors for invasive lesions in a 'see and treat' LEEP with an adjusted odds ratio of 4.68 (95%CI=1.82 to 12.03, P<0.01) and 2.10 (95%CI=1.12 to 3.94, P=0.02), respectively. In conclusion, occult invasive lesion of the cervix was noted in 17% of women with HSIL Pap smear who underwent a 'see and treat' approach at our institute. Unsatisfactory colposcopy and premenopausal status were significant independent predictors of having such lesion.     

Histopathological Outcomes of Women with Squamous Cell Carcinoma on Cervical Cytology

The aim of this study was to determine the final histopathological outcome for women with a squamous cellcarcinoma (SCCA) diagnosed by cervical cytology. The medical records and computerized colposcopic database ofpatients with SCCA on cytology who underwent colposcopy at Chiang Mai University Hospital between February2003 and December 2005 were reviewed and 48 women with SCCA cytology were identified (mean age 50 years,range 31-73). Nineteen (39.6%) women were postmenopausal. Unsatisfactory colposcopy was noted in 42 (87.5%).Thirty one (64.6%) of the patients had a final pathological diagnosis of high-grade squamous intraepithelial lesions(HGSIL), whereas only 16 (33.3%) had invasive cancer. The remaining one patient had a low-grade squamousintraepithelial lesion. Sensitivity and specificity of colposcopic examination for predicting invasive cancer was 50%and 78%, respectively. In conclusion, most women with a SCCA on cervical cytology have high-grade cervical lesionson final pathology, with only one third demonstrating invasive cancer. The loop electrosurgical excision procedure(LEEP) remains an important measure for combined treatment and diagnosis.     

Underlying Histopathology of HIV-infected Women with Squamous Cell Abnormalities on Cervical Cytology

This study was undertaken to evaluate the underlying histopathology of HIV-infected women who hadabnormal cervical cytology. HIV-infected women with abnormal cervical cytology undergoing colposcopy atChiang Mai University Hospital between January 2001 and February 2008 were reviewed. The cohorts werematched and compared with an HIV-negative group. During the study period, 65 HIV-infected women withabnormal cervical cytology were available for review. The abnormal cervical smears were atypical squamouscell (9), low-grade squamous intraepithelial lesion (22), high-grade squamous intraepithelial lesion (27), andsquamous cell carcinoma (7). When stratified by severity of abnormal cytology, HIV-infected women had ahigher risk of having cervical intraepithelial neoplasia II or higher, whether the cervical smear showed lowgrade(P=0.01) or high-grade abnormality (P=0.04) compared with the HIV negative group. After adjustmentby age, parity, and menopausal status, HIV-infected women had 2.56 times the risk of having CIN II or higher(69.2% of HIV-infected women compared with 47.7% of HIV negative women; 95% CI=1.21-5.40, P=0.01). Inconclusion, HIV-infected women with abnormal Pap smears are a population subset with higher risk of significantcervical lesions, irrespective of severity of abnormal cervical smears.     

The Bethesda system and evaluation of abnormal pap smears

The Bethesda Pap Smear system and its 1991 revisions aim to simplify Papanicolaou (Pap) smear reporting and make it more reproducible. It redefines the Pap smear request as a medical consultation. The pathologist consultant is required not only to provide the smear reading but also its clinical recommendation. The Bethesda system insists on a detailed Pap smear report assessing specimen adequacy and types of epithelial changes. Squamous cell abnormalities are grouped according to their biologic potential. Both cervical intraepithelial neoplasia, grade I (CIN I) (mild dysplasia) and human papillomavirus (HPV) lesions are grouped together as low-grade squamous intraepithelial lesions (LGSIL), while moderate and severe dysplasia (CIN II and III) belong to the high-grade squamous intraepithelial lesion (HGSIL) category. Atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance (AGCUS) need further qualification as to whether they favor either a reactive or neoplastic process. Guidelines for management of abnormal Pap smears are discussed in detail.     

Incidence of High Grade Squamous Intraepithelial Lesions in Patients with Atypical Squamous Cells of Undetermined Significance Papanicolaou Smears at Naresuan University Hospital

Purpose: To determine the incidence of high-grade cervical intraepithelial neoplasia (CIN2-3) among patients with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou (Pap) smears. Materials and Methods: One-hundred and eighty-seven patients with ASC-US Pap smears who underwent colposcopy with histological study were enrolled between September 2007 and August 2015. Patient factors (including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners) were obtained. Logistic regression analysis was used to evaluate clinical factors associated with CIN2-3. Results: CIN was diagnosed in 92 of 187 women (49.2%). Sixty-one of these (32.6%) had CIN1 and 31 (16.6%) had CIN2-3. There was no woman who had invasive cancer. There was no correlation of high-grade CIN with factors in this study including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners. Conclusions: Data from this study showed no invasive cervical cancer was found in patients with ASC-US. There was no patient factor associated with high grade intraepithelial neoplasia in patients with ASC-US Pap smears.     

Papanicolaou test interpretations of "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" : an investigation of requisite duration and number of colposcopic procedures to a definitive diagnosis of high-grade dysplasia in routine practice

BACKGROUND: Management guidelines for women with Papanicolaou (Pap) test interpretations of ASC-H (atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion) reflect substantial risk, which ranges from 10% to 68%, of a cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in their follow-up histologic samples. The present study was initiated to determine the number of colposcopic procedures and the time frame that are typically required for a definitive diagnosis of a CIN2+ lesion after a Papanicolaou (Pap) test interpretation of ASC-H in routine practice. METHODS: Clinicopathologic data on consecutive ASC-H interpretations, 97% of which were on liquid-based preparations, were reviewed. The number of biopsies (which was used in this context as a surrogate indicator for the number of colposcopic procedures) as well as the average duration required for a follow-up histologic diagnosis of CIN2+ were determined. RESULTS: Of 500 ASC-H interpretations, 75 were excluded for a variety of reasons and 165 lacked follow-up in our records. The average age and follow-up duration for the remaining 260 patients was 35.6 years and 18.5 months, respectively. CIN2+ was diagnosed in 49 (40%) of the 122 patients with at least 1 histologic follow-up. Of these 49 patients, 72% (35 of 49) were diagnosed on the first follow-up cervical biopsy, 14% (7 of 49) and 8% (4 of 49) were diagnosed on the second and third follow-up biopsies, respectively; in only 6% (3 of 49) was a fourth follow-up biopsy required. Overall, an average of 1.53 biopsies (range, 1-4) was required to attain a definitive diagnosis of CIN2+, and 28% of patients required more than 1 follow-up biopsy. The average period between the index ASC-H interpretations and CIN2+ diagnoses was 5.5 months. The average time to CIN2+ diagnoses by the first follow-up biopsy was 3 months; for diagnoses made on subsequent biopsies, the average additional follow-up duration was 8 months. Of the eventual CIN2+ diagnoses, 84% were rendered within 12 months of their associated index ASC-H interpretations. CONCLUSIONS: 1) A substantial subset-28%-of patients with biopsy-proven CIN2+ after ASC-H interpretations required more than 1 colposcopy for a definitive diagnosis of a high-grade dysplastic lesion. 2) If a CIN2+ lesion is present, the vast majority can be diagnosed in a biopsy performed within 1 year of the ASC-H interpretation.     

Hierarchical clustering of human papilloma virus genotype patterns in the ASCUS-LSIL triage study

Anogenital cancers are associated with ～13 carcinogenic human papilloma virus (HPV) types in a broader group that cause cervical intraepithelial neoplasia (CIN). Multiple concurrent cervical HPV infections are common, which complicates the attribution of HPV types to different grades of CIN. Here we report the analysis of HPV genotype patterns in the atypical squamous cells of undetermined significance-low-grade squamous intraepithelial lesion triage study with the use of unsupervised hierarchical clustering. Women who underwent colposcopy at baseline (n = 2,780) were grouped into 20 disease categories based on histology and cytology. Disease groups and HPV genotypes were clustered with the use of complete linkage. Risk of 2-year cumulative CIN3+, viral load, colposcopic impression, and age were compared between disease groups and major clusters. Hierarchical clustering yielded four major disease clusters: cluster 1 included all CIN3 histology with abnormal cytology; cluster 2 included CIN3 histology with normal cytology and combinations with either CIN2 or high-grade squamous intraepithelial lesion cytology; cluster 3 included older women with normal or low-grade histology/cytology and low viral load; and cluster 4 included younger women with low-grade histology/cytology, multiple infections, and the highest viral load. Three major groups of HPV genotypes were identified: group 1 included only HPV16; group 2 included nine carcinogenic types, plus noncarcinogenic HPV53 and HPV66; and group 3 included noncarcinogenic types, plus carcinogenic HPV33 and HPV45. Clustering results suggested that colposcopy missed a prevalent precancer in many women with no biopsy/normal histology and high-grade squamous intraepithelial lesion. This result was confirmed by an elevated 2-year risk of CIN3+ in these groups. Our novel approach to study multiple genotype infections in cervical disease with the use of unsupervised hierarchical clustering can address complex genotype distributions on a population level.     

Replacing Iodine Staining with Size of Lesion: The Performance of Modified Reid Colposcopic Index

Aim: This study of diagnostic accuracy aimed to assess the performance of authors’ proposing colposcopic index for detecting histological diagnosis of cervical intraepithelial neoplasia grade 2 or worse (CIN2 or worse). Methods: Retrospective analysis of data was carried out on medical records of women who underwent colposcopy in Rajavithi hospital from January 2007 to December 2014. The authors’ proposed score included the first 3 criteria of RCI (margin, color, vascular pattern) and replacing the last RCI criterion (iodine staining) with the detail of size and location of a lesion which was retrospectively retrieved from medical records. Total score for detecting any lesion was ranged from 0-8, similar to the RCI. Performance of the score was assessed for sensitivity, specificity, and positive and negative predictive values at every cut-off level. Results: Among 207 eligible women, 87 (42%) had CIN2 or worse. Cut-off level of score ≥ 6 had a sensitivity, specificity, and positive and negative predictive values of 54.0%,97.5%,94.0%,74.5%, respectively while cut-off value ≥ 2 had sensitivity , specificity, positive and negative predictive values of 94.2% ,55.8% ,60.7%, and 93.0%, respectively, for histological diagnosis of CIN 2 or worse. The area under ROC curve was 0.88. In women with type 3 T-zone, the area under ROC curve was 0.94 which was excellent. Conclusion: The performance of the colposcopic score that replaces iodine staining with the size and location of the lesion is good and practical. High cut-off level can be used in see and treat approach for high-grade squamous intraepithelial lesions. Low cut-off level may be used for omitting biopsy in case of low grade impression. This scoring system seems to have greater performance in womens with type 3 T- zone.     

Reflex Human Papillomavirus Test Results as an Option for the Management of Korean Women With Atypical Squamous Cells Cannot Exclude High‐Grade Squamous Intraepithelial Lesion

Background.

Current guidelines recommend initial colposcopy with biopsy regardless of human papillomavirus (HPV) test results in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of this study was to evaluate the value of HPV testing in women with ASC-H based on colposcopic pathology results.

Materials and Methods.

A multicenter cross-sectional study was carried out at three academic hospitals and involved 40,847 Korean women who underwent cervical cancer screening with cytology and HPV tests with or without subsequent colposcopic biopsies between January 2007 and December 2013.

Results.

ASC-H was diagnosed in 276 women (0.7%). Only 6 of 68 (8.8%) women with ASC-H who were HPV negative had cervical intraepithelial neoplasia grade ≥2 (CIN ≥2) lesions, whereas 47.4% of the women with ASC-H who were HPV positive had CIN ≥2 lesions. No cases of invasive cervical cancer were diagnosed among women with ASC-H who were HPV negative. Logistic regression analysis was performed using the group with normal Papanicolaou test results and HPV-negative status as the reference group. Women with ASC-H who were HPV positive had a significantly increased risk of CIN ≥2 lesions, whereas no significant increase was observed in patients with ASC-H and HPV-negative status.

Conclusion.

If the result of the HPV test was negative, the risk of CIN ≥2 lesions in Korean women with ASC-H cytology was low. Reflex HPV testing should be an option for the management of women with cytology showing ASC-H to decrease unnecessary colposcopic biopsies, which are expensive and invasive.

Implications for Practice:

Current American Society for Colposcopy and Cervical Pathology guidelines recommend universal colposcopy for the management of women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on cytology, regardless of human papillomavirus (HPV) test results. The present study suggested that HPV cotesting in patients with ASC-H cytology can provide more detailed and useful information regarding the risk of high-grade cervical intraepithelial neoplasia (CIN) lesions and the need for further treatment. When the result of the HPV test was negative, the risk of CIN lesions of grade ≥2 in women with ASC-H cytology was low. Consequently, reflex HPV testing, rather than immediately performance of invasive and expensive colposcopy with biopsy, should be an option for the management of women with ASC-H.