Clinical significance of human papillomavirus 16/18 E6 protein detection in shunting and prognosis of patients with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions / 肿瘤研究与临床

Objective To evaluate the value of human papillomavirus (HPV) 16/18 E6 protein detection in shunting and prognosis in patients with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL). Methods A total of 98 patients with ASCUS or LSIL from the Affiliated Cancer Hospital of Shanxi Medical University between May 2014 and May 2015 were selected as the subjects. All of them received the thin-cytologic test (TCT), HPV DNA, HPV16/18 E6 protein tests and colposcopy examination. After 3-year follow-up of patients with cervical intraepithelial neoplasia (CIN) grade Ⅰor bellow lesions diagnosed by biopsy and 30 negative controls, the above tests were performed again. The efficacies of all the tests were analyzed. The value of CIN grade Ⅱ or above was predicted. Results The sensitivity, specificity, positive predictive value and negative predictive value in predicting CIN grade Ⅱor above lesions of HPV16/18 E6 protein , HPV DNA and HPV16/18 DNA was 30.8％, 95.3％, 50.0％, 90.0％, respectively; 84.6％, 37.6％, 17.2％, 94.1％, respectively and 61.5％, 67.1％, 22.2％, 91.9％, respectively in shunting study. The relative risk (RR) of CIN grade Ⅱor above lesions in patients with positive HPV16/18 E6 protein, persistent positive HPV16/18 DNA and positive HPV16/18 DNA was 13.429, 10.231 and 8.343, respectively in the follow-up study. Odds ratio (OR) of HPV16/18 E6 positive protein presenting persistent positive HPV16/18 DNA was 34.833 (95％ CI 5.020-241.711). Conclusions In patients with ASCUS and LSIL, the specificity and positive predictive value of HPV16/18 E6 protein in predicting CIN grade Ⅱ or above lesions are higher than those of HPV DNA and HPV16/18 DNA. Moreover, these patients with HPV16/18 E6 protein positive have a higher risk of developing CIN grade Ⅱ or above lesions and persistent positive HPV16/18 DNA.

Study on HPV infection types distribution in ASC-US ,LSIL and HSIL of uterine cervix / 国际检验医学杂志

Objective To analyze the genotypes distribution and clinical significance of human papillomavir-us(HPV) infection in atypical squamous cells of undetermined significance (ASC-US) ,low squamous intraepi-thelial lesion (LSIL) and high squamous intraepithelial lesion (HSIL) of uterine cervix ,meanwhile to conduct the cervical histopathological diagnostic analysis in the patients with ASC-US、LSIL and HSIL .Methods The gene amplification technique (PCR) combined with gene-chips technology were adopted to conduct the 23 kinds of HPV genotype detection on 236 cases of cervical ASC-US ,36 cases of cervical LSIL and 61 cases of cervical HSIL specimens .All cases of ASC-US ,LSIL and HSIL were performed the cervical biopsy his-topathological diagnosis .And then the subjects related data were analyzed .Results Among 236 cases of cervi-cal ASC-US specimens ,139 cases of HPV infection were detected with the total HPV infection rate 58 .90％(139/236) ,in which the single genotypes infection rate was 38 .14％ (90/236)and the multiple genotypes infec-tion rate was 20 .76％ (49/236);26 cases of HPV infection were detected from 36 cases of cervical LSIL speci-mens with the total HPV infection rate of 72 .22％ (26/36) ,in which the single genotypes infection rate was 52 .78％ (19/36) and the multiple genotypes infection rate was 19 .44％ (7/36);61 cases of HPV infection were detected from 58 cases of cervical HSIL specimens with the total HPV infection rate of 95 .08％ (58/61) , in which the single genotypes infection rate was 68 .85％ (42/61)and the multiple genotypes infection rate was 26 .23％ (16/61) .The total infection rates had statistically significantly differences among the cervical ASC-US group ,LSIL group and HSIL group (P<0 .05) .Conclusion HPV16 ,52 ,58 are the main types in the patients with cervical ASC-US ,LSIL and HSIL .The gene-chip technology can be used in the HPV genotypes detection of cervical cells ,which has an important clinical significance for further distribution management on ASC-US patients and should draw great attention of gynecologist .

Risks of cervical intraepithelial neoplasia grade 3 or invasive cancers in ASCUS women with different management: a population-based cohort study / 부인종양

OBJECTIVE: To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. METHODS: Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). RESULTS: There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07–0.68; p=0.010). Women in their 40s–50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03–1.49; p=0.020). CONCLUSION: In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years.

Comparison of the PANArray HPV Genotyping Chip Test with the Cobas 4800 HPV and Hybrid Capture 2 Tests for Detection of HPV in ASCUS Women

PURPOSE: This study aimed to evaluate the performance of the PANArray human papilloma virus (HPV) test, a PCR-based DNA microarray assay, in detecting HPV from patient samples and its concordance with the cobas 4800 HPV and Hybrid Capture 2 (HC2) tests. MATERIALS AND METHODS: The PANArray HPV, cobas 4800 HPV, and HC2 tests were performed on 504 cervical swab samples from patients with atypical cells of undetermined significance at five hospitals. The samples that were interpreted as ‘HPV-other’ type positive in the PANArray HPV test were confirmed by direct sequencing. RESULTS: The concordance rates were 80.8% between the cobas 4800 HPV and PANArray HPV tests [κ=0.59, 95% confidence interval (CI) 0.52–0.66] and 80.2% (κ=0.6, 95% CI 0.55–0.68) between the HC2 and PANArray HPV tests. Among the 62 patients negative on PANArray HPV (defined as the absence of high risk HPV), but positive on both cobas 4800 HPV and HC2 tests, 42 (67.7%) tested positive for ‘HPV-other’ types on the PANArray HPV test, and 31 (50.0%) had gray zone results [relative light unit/control (RLU/CO), 1.4–9.25] in the HC2 test. Of the patients deemed positive by the PANArray HPV test, 43 tested positive for high-risk (HR) HPV in cobas 4800 HPV and HC 2 tests. Among them, 58.2% showed HR HPV, including HPV 16, by direct sequencing, of which 25% had gray results. CONCLUSION: Results classified as ‘HPV-other’ type by the PANArray HPV test, or gray zone results by HC2 (RLU/CO ratio level 1–10) should be carefully interpreted using comprehensive clinical information.

Atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion triage in Korean women: Revisiting the 2012 American Society of Colposcopy and Cervical Pathology screening guidelines

OBJECTIVE: To determine whether triage for atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) from the updated American Society for Colposcopy and Cervical Pathology cervical cancer screening guidelines is applicable in Korean women. METHODS: We investigated women with ASC-US or LSIL including referred from local hospitals visited for cervical cancer screening at Korea University Guro Hospital from February 2004 to December 2014. Detailed information on the results of Papanicolaou (Pap) smears, human papillomavirus (HPV) DNA tests, and cervical biopsies were collected through chart review. Cervical biopsy results were compared in eligible women according to individual Pap smear findings and HPV DNA status. RESULTS: Of 216,723 possible cases, 3,196 were included. There were 212 (6.6%) women with ASC-US and 500 (15.6%) with LSIL. The risk of ≥cervical intraepithelial neoplasia (CIN) 2 was significantly higher in women who were ASC-US/HPV+ than ASC-US/HPV- and LSIL/HPV+ than LSIL/HPV- (93.3% vs. 6.7% and 96.7% vs. 3.3%, P<0.001 and P<0.001, respectively). The risk of ≥CIN 3 was also significantly higher in women who were ASC-US/HPV+ than ASC-US/HPV- and LSIL/HPV+ than LSIL/HPV- (97.0% vs. 3.0% and 93.0% vs. 7.0%, P<0.001 and P<0.001, respectively). Age-stratified analysis revealed that more CIN 2 or CIN 3 was diagnosed in women aged 30 to 70 with ASC-US or LSIL when HPV DNA was present. CONCLUSION: Observation with Pap and HPV DNA tests rather than immediate colposcopy is a reasonable strategy for ASC-US or LSIL when the HPV DNA test is negative, especially in women aged 30 to 70. Reflection of these results should be considered in future Korean screening guidelines.

Exploring in management of women with atypical squamous cells of undetermined significance / 实用医学杂志

Objective Exploring in processing method to triage of women with a cytologic smear showing atypical squamous cells of undetermined significance. Methods All 130 cases were diagnosed with ASCUS received high-risk HPV (hr-HPV)test, colposcopic inspections, reformeded Reid's colposcopic index score and cervical biopsies for pathological examination. Resluts The pathology of 130 ASCUS patients included 31cases of normal and inflammation (23.90%), 29 cases of CINⅠ(22.30%), 14 cases of CINⅡ(10.80%), 55 cases of CINⅢ or cervical carcinoma in situ (42.30%), and 1 case of invasive cervical carcinoma (0.80%). The reformed Reid's colposcopic index score of 130 ASCUS patients included 32 cases of 0 score (24.60%), 36 cases of 1~2 scores (27.70%), 47 cases of 3~4 scores(36.10%), 15 cases of 5~6 scores(11.60%). 2. The colposcopy used to detect the CIN of ASCUS, its sensitivity was 98.99%(98/99), specificity was 51.61%(16/31). The hr-HPV used to detect the CIN of ASCUS, its sensitivity was 96.97%(96/99), specificity was 32.26%(10/31). Conclusion Both the reformeded Reid′s colposcopic index score and hr-HPV testing as the clinical triage methods of ASCUS. The former has good sensitivity and specificity ,which is superior to hr-HPV testing.

The importance of immediate verification of a cervical cytological abnormality with histology.

Background: A serious proportion of the patients with invasive cervical cancer can be women who have had abnormal smear findings known for at least 6 months. Aims: The aims of the study were to evaluate the cervical cytohistopathologic correlation in the population studied, and to discuss the acceptability of immediate histological verification for minor Papanicolaou smear abnormalities. Materials and Methods: A total of 443 patients who were admitted with abnormal smear results and had undergone immediate colposcopy, cervical biopsy and endocervical curretage in the gynecologic oncology clinic between the years of 2003-2009 were enrolled into the present retrospective study. One-way analysis of variance and independent t-tests were used to study the results. Results: The distribution of abnormal smear results were documented as 46.27%, 29.57%, 13.76%, 7.67%, 1.58%, 0.67%, and 0.45% for atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H), squamous cell carcinoma (SCC), atypical glandular cell (AGC), and adenocarcinoma, respectively. The percentages of cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) and greater lesions were 70.49%, 35.29%, 15.26%, and 9.75% for HSIL, ASC-H, LSIL, and ASC-US, respectively. Moreover, 38.36% of all the CIN 2-3 or cancer (n = 104) cases originated from those with low grade referral diagnosis (ASC-US and LSIL). Conclusions: The majority of cases in the study were predominantly ASC-US and LSIL and approximately 40% of all the high grade lesions came from those with low grade referral diagnosis. This shows poor cytohistopathological correlation and calls the triage of minor cytological abnormalities into question.

Analysis of the Histopathology of ASCUS Diagnosed by Liquid-based Cervical Cytology / 昆明医科大学学报

Objective To analyze the histopathology of patients with atypical squamous cells of undetermined significance (ASCUS),and provide evidence for further classification and clinical treatment of ASCUS.Methods The histopathology of cervical biopsy specimens from 249 patients with ASCUS diagnosed by liquid-based cervical cytology examination was analyzed retrospectively. Results Among the 249 ASCUS patients, the proportion of patients with inflammation was 34.14% (85/249), morphological change by human papillomaviral infection was 19.28%(48/249), CIN I was 32.53%(81/249),CIN II was 8.84%(22/249),CIN III was 3.21%(8/249), infiltrating squamous cell carcinoma was 1.20%(3/249),and endometrioid adenocarcinoma was 0.80%(2/249) . Conclusion It is very important to to further definitude the diagnosis of ASCUS, because a certain proportion of cervical cancer and precancerous leisions woud be confirmed.

Infección por virus papiloma humano en pacientes con células escamosas atípicas de un programa de pesquisa de cáncer cervical / Human papilloma virus infection in patients with atypical squamous cells of a screening program for cervical cancer

Evaluar la frecuencia de la infección por virus del papiloma humano en pacientes con células escamosas atípicas de un programa de pesquisa de cáncer de cuello uterino. Laboratorio Asistencial “Lic. Celina Sánchez Rincón y Laboratorio de Biología y Medicina Experimental LABIOMEX. Universidad de Los Andes. Mérida, Estado Mérida. Estudio prospectivo y descriptivo que incluyó las pacientes vistas entre marzo de 2006 y diciembre de 2009. Se tomaron muestras para evaluación citológica y detección del virus papiloma humano, mediante la metodología molecular PCR-RFLP a pacientes de pesquisa de cáncer cervical. Se estudiaron 2 805 pacientes seleccionándose las que presentaron informe citológico de células escamosas con atipias de significado indeterminado y con atipias que no excluyen lesión intraepitelial escamosa de alto grado. Del total de mujeres evaluadas por citología, 121 (4,31 por ciento) tenían informe de anormalidades en células epiteliales. Las células escamosas atípicas se encontraron en 58 (2,06 por ciento) citologías, 52 (1,85 por ciento) eran células escamosas con atipias de significado indeterminado y 6 (0,21 por ciento) eran células escamosas con atipias que no excluyen lesión intraepitelial de alto grado. La prevalencia general de la infección por virus del papiloma humano fue de 32/58 (53,4 por ciento). Los virus del papiloma humano de alto riesgo oncogénico se encontraron en 10/58 (17,2 por ciento) de los casos, la mayoría en el grupo etario de 21-30 años. No se pudo determinar el tipo viral en un 16/58(27,5 por ciento) de las muestras. Se observó una elevada prevalencia de virus del papiloma humano en pacientes con informe citológico de células escamosas atípicas.

To evaluate the frequency of human papillomavirus infection in patients with atypical squamous cells of a cervical cancer detection program. Between March 2006 to December 2009, specimens for cervical smears and human papillomavirus molecular detection by PCR-RFLP were taken from the patients attended at the cervical cancer clinic prevention. Facultad de Farmacia y Bioanálisis. Laboratorio Asistencial “Lic. Celina Sánchez Rincón y Facultad de Ciencias, Laboratorio de Biología y Medicina Experimental LABIOMEX. Universidad de Los Andes. Mérida, Estado Mérida, Venezuela. A total of 2 805 patients were evaluated, those with atypical squamous cells of undetermined significance and atypical squamous cells that cannot exclude a high intraepithelial lesion were chosen. Abnormalities in epithelial cells were found in 4,31 percent. Atypical squamous cells were found in 58 (2,06 percent) of the cases, 1,85 percent were atypical squamous cells of undetermined significance and 0,21 percent were atypical squamous cells that cannot exclude a high intraepithelial lesion. The overall prevalence of human papillomavirus infection was 32/58 (53,4 percent). High risk human papillomavirus was found in 10/58 (17,2 percent)of the patients, most of them between 21 and 30 years old. Human papillomavirus could not be determinedin 16/58 (27,5 percent) of the cases. It was observed a high frequency of human papillomavirus in patients with atypical squamous cells in their cervical smears.

The value of high-risk human papillomavirus detection in women with atypical squamous cell of undetermined significance / 中国医师进修杂志

Objective To evaluate the triage value of high-risk human papillomavirus (HR-HPV)detection in women with atypical squamous cells of undetermined significance (ASCUS).Methods Two huandred women with atypical squamous cells of undetermined significance (ASCUS) were selected by thinprep cell test(TCT) simultaneously using HPV DNA testing by hybrid capture Ⅱ (HC) and biopsy under the colposcopy,compared the HR-HPV DNA testing with final pathological diagnosis.CIN (cervical intraepithelial neoplasia) means cervical biopsy positive.Results The positive rate of cervical biopsy in HPV positive patients was 60.38％(96/159),and in HPV negative patients was 21.95％(9/41),the difference was obviously (P ＜ 0.05).Conclusion HR-HPV detection is a good triage approach for the patients with ASCUS.

Células Escamosas Atípicas de Significado Indeterminado: un citodiagnóstico subjetivo / Atypical Squamous Cells of Undetermined Significance: A subjective cytodiagnosis

El objetivo del presente trabajo es intentar la disminución de la subjetividad que acompaña al citodiagnóstico de células escamosas atípicas de significado incierto (ASCUS) por medio de un parámetro que pueda ser medido y sea útil como valor pronóstico. A 20 extendidos provenientes de cuello uterino coloreados con la técnica de Papanicolaou con diagnóstico de ASCUS (11 metaplasias atípicas, 6 casos de HPV con atipías y 3 casos de anomalías marcadas por hipoestrogenismo) se les aplicó la técnica de AgNOR (regiones del organizador nucleolar afines a Ag) y el área de AgNOR fue medida por citometría de imágenes. Los resultados fueron: 6,0 µ², s=1,60 µ² para metaplasia atípica, 0,90 µ², s=1,05 µ²para HPV con atipías y no detectable para extendidos hipoestrogénicos. Las diferencias entre áreas promedio fueron evaluadas con el test de Student. Se propone 4,4 µ² como valor de corte del área de AgNOR como índice de progresión de las metaplasias atípicas. Los casos de HPV con atipías son insuficientes para definir algún valor de área, y en las pacientes con anomalías marcadas por hipoestrogenismo se recomienda la repetición del extendido post-estímulo estrogénico.

The objective of this paper is to diminish the subjectivity of ASCUS (Atypical Squamous Cells of Undetermined Significance) diagnosis by means of a parameter useful in the prognosis of the pathology. AgNOR technique was applied to 20 cytologic smears from uterine cervix stained by Papanicolaou method and with ASCUS diagnosis: 11 atypical metaplasias, 6 with atypical keratinizing cells related to human papillomavirus (HPV) infection and 3 with regressive changes by estrogen deficiency. The AgNOR area was determined by image cytometry. The mean AgNOR areas were: 6.0 µ², s=1.60 µ² for atypical metaplastic cells, and 0.90 µ², s=1.05 µ² for smears with HPV with atypical keratinizing cells. AgNOR areas were not measurable in the cases of estrogen deficiency. Differences in the mean AgNOR protein areas were tested by Student's test. The cut-off value proposed for smears with atypical metaplastic cells is 4.4 µ² as a limit of progressive lesions. It was not possible to establish a value for cases with atypical keratinizing cells related to HPV because of the low number of smears. In estrogen deficiency, it is advisable to perform the estrogenic stimulus before taking any decision.

The significance of Human Papillomavirus viral load by using hybrid capture II assay in diagnosis of CIN II or above in women with PAP smear showing only ASCUS/LSIL / 대한산부인과학회지

OBJECTIVE: To determine the clinical significance of high risk Human papillomavirus (HPV) DNA viral load measured by hybrid capture (HC) II assay in diagnosis of CIN II or above in women with cervical smear showing only Atypical squamous cells of undetermined significance (ASCUS)/Low-grade squamous intraepithelial lesion (LSIL). METHODS: This study was performed from September 2003 to September 2004 and included 111 patients with ASCUS/LSIL on PAP smear. All of them underwent high risk HPV DNA tests by HC II assay and colposcopy directed cervical biopsies. The histologic results were classified as low grade lesion (normal, CIN I) and high grade lesion (CIN II, III, and invasive cancer). The viral load was transformed into their logarithm (Log10RLU/PC ratio), and categorized as following four groups; negative HPV DNA (Log10RLU/PC or =2.0). We evaluated the relationships of the detection rate and viral load of high risk HPV DNA with histologic severity of cervical lesions. RESULTS: The rate of CIN II or above in 111 patients with ASCUS/LSIL was 25.2%. The detection rate of high risk HPV DNA using HC II assay was 96.4% in high grade lesion, and 66.3% in low grade lesion of histologic test. There was strong correlation between CIN II or above and positivity for HPV DNA when this group was compared with women with only CIN I or normal cervix (OR:13.7, 95% CI:1.7-106.4). The higher the viral load of HPV DNA infection observed, the higher the probability of being associated with stage of CIN (correlation coefficient:0.279). The frequency of high viral load observed in high grade lesion (89.3%) was significantly higher than low grade lesion (33.7%)(OR:16.3, 95% CI:4.5-58.9). When the cutoff of positivity was changed from 1.0RLU/PC ratio to 100.0RLU/PC ratio (Log10 RLU/PC ratio=2.0), the sensitivity for the prediction of high grade lesion was slightly decreased (96.4->89.3%), but pronounced gain in specificity (33.7->66.3%), and reduction in false positive rate (66.3->33.7%). CONCLUSION: The viral load of high risk HPV DNA measured by HC II assay was significantly associated with the severity of histology, and useful in diagnosis of CIN II or above in women referred because of ASCUS/LSIL on PAP smear.

The efficacy of HPV DNA chip test in the atypical squamous cell of undetermined significance / 부인종양

OBJECTIVE: This study was performed to investigate the efficacy of DNA chip method for detecting and genotyping of human papillomavirus (HPV) and screening of high-grade CIN (cervical intraepithelial neoplasia) or invasive cancer in the patients with atypical squamous cells of undetermined significance (ASC-US). METHODS: This study was based on 131 cases to be revealed ASC-US by Pap smear for the cervical cancer screening from July 2004 to Octorber 2004. They were evaluated by HPV DNA chip test, Cervical colposcopy and directed biopsy, and cone biopsy. The results of type 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 54, 56, 58, 59, 66 and 68 in HPV DNA chip test were categorized as high risk HPV. We evaluate the detection rate of the high-grade CIN and invasive cancer by HPV DNA chip test. RESULTS: The incidence of high risk HPV DNA was 51.1% (67/131). Twelve of 131 (9.2%) were diagnosed as high-grade CIN or CIS on histology. The detection rate of high risk HPV DNA in high-grade CIN and invasive cancer was 83.3% (10/12). The detection rate of high risk HPV DNA was 36.0% (31/86) in normal or reactive, and 83.3% (10/12) in CIN II or above on histology. Higher the grade of biopsy, more the detection rate of high risk HPV DNA by HPV DNA chip test. CONCLUSION: The use of HPV DNA chip test in patients with ASC-US may be useful in detection of high-grade CIN or invasive cancer.

Clinical Significance of HPV DNA test for Management of Patients with Diagnosis of Atypical Squamous Cells of Undetermined Significance/Low-grade Squamous Intraepithelial Lesions / 대한산부인과학회잡지

OBJECTIVE: This study was performed to evaluate the clinical efficacy of high risk HPV DNA test using PCR for the detection of high-grade CIN or invasive cancer from patients with ASCUS or LSIL on Papanicolaou smear. METHODS: Sixty one patients with a Papanicolaou smear report of atypical squamous cells of undetermined significance or a low-grade squamous intraepithelial lesion underwent Cervical colposcopy and directed cervical biopsy and human papillomavirus test by PCR. We compared the detection rate of the high grade CIN and invasive cancer by Papanicolaou smear method only with that of both Papanicolaou smear and HPV PCR method. and we decided to be significant when P value was below 0.05 by SAS (v 6.02) program. RESULTS: The detection rate of high risk HPV DNA was 50.8% (31/61). The detection rate of high risk HPV DNA in high grade CIN and invasive cancer was 84.2% (16/19). Higher the grade of biopsy, more the detection rate of high risk HPV DNA. False negative rate which appeared high grade CIN or invasive cancer by biopsy was 31.2% (19/61) in Papanicolaou smear method only and 4.9% (3/61) in both Papanicolaou smear and HPV DNA method. CONCLUSION: We thought that additional HPV DNA test was useful to dectect behind high grade CIN or invasive cancer when the Papanicolaou smear result was ASCUS or LSIL.

The Clinical Significance and The Optimal Management of Atypical Squamous Cells of Undetermined Significance in Cervical Smears / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinical significance and the optimal management of atypical squamous cells of undetermined significance (ASCUS) in Papanicolaou cervical smears. METHOD: This study included 25380 cases of cervical Pap smears received from January 1995 to June 2000 by the Department of Obstetrics & Gynecology, Inha Hospital, Medical College, the Inha University. Retrospective review was done on 384 cases of ASCUS. RESULT: ASCUS and squamous intraepithelial lesions (SIL) were diagnosed in 384 cases (1.5%), and 311 cases (1.1%), respectively. The ratio of ASCUS to SIL was 1.2. Colposcopic directed biopsies revealed 14 cases (14.1%) of low grade SIL (LSIL), 21 cases (21.2%) of high grade SIL (HSIL), and 2 cases (2.0%) of squamous cell carcinoma. CONCLUSION: The immediate colposcopy with biopsy in women with ASCUS may decrease follow-up visits for Pap testing, reduce patient anxiety, minimize the loss of high risk cases during follow-up and lower medicolegal litigation. The early colposcopy may be the method of choice for follow-up in women with ASCUS in Korea.

The Clinical Significance of The Qualification of Atypical Squamous Cells of Undetermined Significance (ASCUS) in Cervicovaginal Smears / 대한산부인과학회잡지

OBJECTIVE: The Bethesda System (1991) recommended that the diagnosis of atypical squamous cells of undetermined significance (ASCUS) be qualified when possible to indicate whether a reactive process, or premalignant/malignant process, is favored. In order to evaluate the clinical significance of the qualification, we reviewed our hospital's experience with cervicovaginal smears diagnosed as ASCUS. METHOD: A retrospective study from June 1994 to December 2000 was performed on all cervicovaginal smears with the diagnosis of ASCUS. 3759 cases were included in study group. The 1200 cases of 3759 were not followed up. Histopathologic diagnosis and cervicovaginal smear results were reviewed and compared according to the qualification of ASCUS. The Chi-square test was used. RESULTS: Histopathologic diagnosis of low-grade squamous intraepithelial lesion (LGSIL) was seen in 46.1%, 47.8%, and 44.3% of the ASCUS FR, ASCUS FD and ASCUS NOS group, respectively. Histopathologic diagnosis of high-grade squamous intraepithelial lesion (HGSIL) was seen in 6.0%, 17.2% and 7.8% of the ASCUS FR, ASCUS FD and ASCUS NOS group, respectively. In ASCUS FR group, 1 invasive carcinoma was detected. In ASCUS FD group, 6 carcinoma in situ (CIS), 2 microinvasive carcinoma, 1 invasive carcinoma and 1 adenosquamous cell carcinoma were detected. In ASCUS NOS group, there were 20 CIS, 5 microinvasive carcinoma, 7 invasive carcinoma and 2 invasive adenocarcinoma. The ASCUS FD group demonstrated significant risk for SIL and more severe lesion but ASCUS FR and ASCUS NOS demonstrated no significant difference. CONCLUSION: ASCUS FD group has increased risk for detection of SIL or more severe lesion than ASCUS FR or ASCUS NOS group. But there were also significant number of SIL and even invasive cancer in ASCUS FR and ASCUS NOS group, so qualification of ASCUS was not useful for management and colposcopy-directed biopsy is advocated even in ASCUS FR group.

Chromosomal Abnormality of Spontaneous Abortus in Relation to Transvaginal Ultrasonographic Finding / 대한산부인과학회잡지

OBJECTIVE: To determine the clinical value of human papillomavirus deoxyribonucleic acid(HPV DNA) testing by polymerase chain reaction(PCR), specifically to examine whether HPV testing could identify the women with Pap smears read as mostly atypical squamous cells of undetermined significance(ASCUS) or more. METHODS: HPV DNA testing by PCR for 3 high-risk cancer associated genotypes(HPV 16, 18, 33), repeat Pap smears and colposcopically directed punch biopsies were performed concurrently on 169 women referred for cervical cancer screening test with a previous Pap smear read as ASCUS or more. RESULTS: HPV DNA testing positivity was significantly associated with abnormal cytology and high-grade squamous intraepithelial lesion(HSIL) and squamous cell carcinoma(SCC) in histology(P=0.034). The sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV) of Pap smear and HPV testing for identifying 38 cases of histologically confirmed HSIL and carcinoma by different triage protocols(HPV positive or HSIL or SCC) among 169 women were 65.8%(25/38), 85.5%(112/131), 56.8%(25/44) and 89.6%(112/125), respectively. Also sensitivity, specificity, PPV and NPV were varied by ages and more higher in older. CONCLUSION: HPV DNA testing by PCR appears to offer an effective means by which women whose cervical Pap smears have been read as ASCUS or more could be triaged for colposcopically directed biopsy. The sensitivity for HSIL could be maintained in high and specificity markedly improved by HPV genotypes 16, 18, 33.

The Analysis of Risk Factors and Significance of Tumor Necrosis Factor(TNF)-a in Henoch-Schonlein Nephritis

A mediastinal mass was aspirated by fluoroscope-guided fine needle aspiration biopsy in a 47 years old female patient. The first aspiration smears were not diagnostic, because of hemorrhagic background and cell paucity. On the second aspiration, the smears were composed of some clusters of benign epithelial cells in hemorrhagic background. Cells were arranged in mostly solid sheets and tended to form glandular lumina in part. Their nuclei were round and vesicular. Nucleoli were not prominent. These findings were suggestive of benign glandular tissue, which was finally confirmed as mediastinal thyroid gland by open thoracotomy specimen.

Comparison of Qualified Diagnosis of "Atypical Squamous Cells of Undetermined Significance" with Subsequent Biopsy / 대한세포병리학회지

To evaluate whether different qualifications of a cytologic diagnosis of "atypical squamous cells of undetermined significance(ASCUS)" predict a greater or lesser likelihood of tissue diagnosis of uterine cervix, we compared different cytologic qualifications of ASCUS with the tissue diagnosis. One hundred twenty-two con secutive Papanicolaou smears showing ASCUS in women who had undergone cervical biopsy within nearest 30 days were collected. The 122 smears were qualified as "favor reactive"(25%), "favor low grade squamous intraepithelial lesion (LSIL)"(24%), "favor squamous intraepithelial lesion(SIL)"(16%), "favor high grade squa mous intraepithelial lesion(HSIL)"(16%), and "not otherwise specified"(19%). Squamous intraepithelial or invasive lesion was pathologically confirmed by cervical biopsy in 13% of the "favor reactive", 27% in "favor LSIL", 70% in "favor SIL", 75% in "favor HSIL", and 35% in "not otherwise specified" smears. There were significant asso ciations between the favor reactive smear and the benign biopsy finding and between the favor SIL smear and the biopsy showing a squamous intraepithelial or more severe lesion. Nevertheless, most of favor LSIL smears exhibit reactive process in tissue biopsy. Conclusively, qualified ASCUS stratifies women into different risk groups for SIL. The cytopathologist should make the cytologic diagnosis of "ASCUS, favor LSIL" circumspectly.

Histologic and Cytologic Follow-up in Atypical Squamous Cells of Undetermined Significance(ASCUS) on Cervical Smears / 대한세포병리학회지

In 1988, The Bethesda System for reporting cervical and vaginal cytologic diagnoses was introduced and this was revised in 1991. The new diagnostic category "atypical squamous cells of undetermined significance(ASCUS)" introduced by The Bethesda System is an area of controversy about the diagnostic category, clinical significance and appropriate treatment. A retrospective 2 years and 9 months study(April,1994-December,1996) was performed to evaluate the significance of reporting ASCUS on cervical smears. Sixtyseven(1.17%) of 5,730 smears were diagnosed as ASCUS and 21 cases were followed by cervical biopsies and/or endocervical curettages in 4 cases(19%), and repeat cervical smears in 17 cases (81%). Tissue diagnoses were benign in 2 cases and squamous cell carcinoma in situ in 2 cases. Cytologic diagnosis of follow up smear were negative in 14 cases (82.4%) and persistent ASCUS in 3 cases(17.6%).