한국형 자궁경부 촬영진 ( New Cervicography ) , 세포검사 그리고 HPV-DNA 검사를 이용한 새로운 자궁경부암 검진 모델 ( Model ) 개발

김승조(SJ Kim),박찬규(CK Park),이효표(HP Lee),남궁성은(SE Namkoong),강순범(SB Kang),서호석(HS Saw),이재관(JK Lee),김수녕(SN Kim),김재원(JW Kim),배석년(SN Bae),김찬주(CJ Kim),이근호(KH Lee),이선영(SY Lee),김인호(IH Kim),이찬(C Lee),이정노(JN Lee) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.5

N/A Objective : The false negative rate of conventional cytology is reported to range from 18 to 45%. It is necessary to develop more effective screening strategies that would ideally be more accurate than conventional cytology. This study is designed to investigate the potential of conventional cytology, cervicography, HPV-DNA testing and their combinations as primary screening techniques for cervical neoplasia. The purpose of this project is to develop the models and guidelines for screening tools of cervical cancer of the uterus by evaluating sensitivity, specificity and cost-effectiveness of all the screening methods. Study design : We conducted a screening of random sample of women who visited the department of OB-Gyn. of five different major university hospitals such as Catholic University Hospital, Korea University Hospital, Seoul National University Hospital, Yeonsei University Hospital and Pochon CHA University Bundang CHA Hospital, from May 1, 1996 to April 30, 1999. In a cohort women with an age range of 20 to 70 who underwent routine cytologic screening at Catholic University, Hospital Bundang CHA General Hospital and local clinics from April 1, 1996 to Decomber 31, 2000. cervicography (n=417,125) and testing for HPV-DNA (n=1,347) by the hybrid capture assay were studied for the ability of the cervical cancer screeuing. A new cervicography system with Kim's classification which was developed by Prof. Kim Seung Jo as an adjunctive method for the cervical cancer screening was applied in this cohort study. And then, accuracy, effectivencess, cost-effectiveness of the single or combined screening method were analysed. Result : Sensitivity and specificity of Pap smear were ranged from 55.6% to 83.1% and 72.8% to 88.3% respectively. The combination of Pap smear and cervicography had sensitivity from 89.7% to 98.6%, specificity from 68.2% to 93.2%. With combination of Pap smear, HPV DNA test and cervicography, sensitivity became also highest accuracy among all screening methods from 92.8% to 98.8%. Considering medical charges for diagnosis and social cost occurred by false positive and false negative results, the most cost-effective diagnostic modality was thought to be the combination of Pap smear and cervicography(91,433 won). In patients who were diagnosed as LSIL, colposcopic examination confirmed progression to high grade intraepithelial lesion(HSIL) in 10.7% patients, persistence of LSIL in 55% patients during the 3 year follow-up period. Accuracy of the screening for cervical cancer and CIN can significantly be improved by cytology with new cervicography rather than cytology alone. We concluded that cervicography can be important adjunctive tests for cervical cytology, improving the effectiveness of cervical screening by allowing a more sensitive detection of cervical neoplasia.

임신부 빈혈치료에 있어서 Iron Protein Succinylate (Hemo-Q) 의 임상적 효과

김장흡,김수평,김진홍,김휘준,김찬주,박미숙 대한산부인과학회 1994 Obstetrics & Gynecology Science Vol.37 No.5

Iron protein succinylate (Hemo-Q) is a new iron preparation for oral administration. Clinical efficacy and safety of iron protein succinylate were evaluated in 40 pregnancy and postpartum women under serum hemoglobulin level 10 gm/dl. The aim of this study was to assess the efficacy and tolerability of iron protein succinylate in iron deficiency anemia of pregnant and postpartum women. Most women received 2 bottles (30ml) every day for 60 days. Improvement was measured by hematologic variables and clinical symptom or sign after 30 days and 60 days respectively. In Conclusion 1. Efficacy of iron protein succinylate showed significant difference among pretreatment, 30 and 60 days treatment group in serum hemoglobulin and iron level. 2. Improvement of clinical symptom (polypnea, asthenia, anorexia) and sign (cutaneous, mucous pallor) of iron deficiency anemia were noted in both 30 and 60 days treatment. 3. Side effects (vomiting, constipation, diarrhea, gastric discomfort) were reported with 1(2.5%) to 2(5%) of 40 women.

자궁경부암 환자에서 ELISA를 이용한 HPV-16 VLP에 대한 혈청반응

김승조,남궁성은,박종섭,김현수,김찬주,박순희,안희경,황은성,정근택 대한산부인과학회 1996 Obstetrics & Gynecology Science Vol.39 No.1

1993년 1월부터 1994년 12월까지 가톨릭대학교 의과대학 강남성모병원 산부인과 종양학부에서 진단 및 치료를 받았던 환자들에서 치료전 채취한 혈청과 자궁경부 세포를 이용한 실험결과 다음과 같은 결론을 얻을 수 있었다. 1. 자궁경부암 전구병변 환자 20명은 HPV-16에 양성이었고, 나머지 4명은 다른 아형의 DNA HPV가 있거나, 발견되지 않았다. 96명의 자궁경부암 환자에서 69명은 HPV-16 DNA, 9명은 HPV-18 DNA에 양성이었고, 그외 3명은 HPV-16과 HPV-18이 동시에 발견되었다. 또한 7명에서는 다른 아형의 HPV DNA가 있었고, 나머지 8명은 HPV DNA를 발견할 수 없었다. 2. HPV-16 L1, L2 VLP에 대한 ELISA 결과는 정상 대조군의 9%에서 양성이었고, 자궁경부 전구병변의 환자에서는 50%(12/24), 자궁경부암 환자의 62.5%에서 각각 양성으로 나타나 자궁경부의 종양성 변화가 있는 환자에서 유의한 진단적 가치가 있었다. 3. HPV-16 DNA에 양성인 자궁경부암 환자의 68%(47/69)에서 HPV-16 VLP ELISA에 양성이었고, HPV-18 DNA에 양성인 환자의 44%(4/9)에서 HPV-16 VLP ELISA에 양성이었으나 HPV-16/18이외의 다른 HPV 아형에 양성인 환자에서는 14%(1/7)에서 ELISA 양성으로 나타나서 HPV-16또는 HPV-18 DNA 양성인 환자들과 다른 종류 HPV DNA에 양성인 환자들 사이에서 항체 반응 여부는 통계학적인 차이가 있었다. 4. 자궁경부암 환자의 임상기와 조직학적 특성에 따른 HPV-16 VLP에 대한 항체 형성을 관찰해 본 결과 각 임상기와 조직형에 따른 차이를 관찰할 수 없었다. 이상의 결과로 자궁경부암과 전구 병변 환자들의 대다수에서 ELISA 방법으로 HPV-16 VLP에 대한 항체 형성을 관찰할 수 있었다. 또한 HPV-16 VLP ELISA 검사는 HPV-16 DNA 검사의 보조진단법으로 유용하며, HPV와 연관된 자궁경부 종양성 질환의 혈청학적 역학 연구에도 도움을 줄 수 있을 것으로 사료된다. Background: The late structural proteins of HPV-16 have recently been shown to self-assemble into virus-lide particles(VLPs) from baculovirus system when expressed in insect cells. The ability to generate preparative amounts of HPV-16 L1-L2 VLP may have implications for the development of a serologic assay to detect anti-HPV-16 virion immune responses to conformational epitopes and for immunoprophylasis against HPV-16 infection. Methods: We attempted to investigate serologic responses in the sera obtained from Korean women with cervical neoplasia by ELISA using HPV-16 VLPs. PCR method using L1 consensus primers and type-specific oligomer probes was used to determine the presence and type of HPV infection in the study population(normal control; 23 cases, preinvasive lesions; 24 cases, and invasive cervical cancers; 96 cases). Result: 1) The sera of 93%(21/23) of women, who didn`t have HPV-ralated cervical lesions, were negative for HPV-16 VLPs in ELISA assay. The sera of 50%(12/24) of patients with preinvasive cervical lesion and 63%(60/96) of patients with invasive cervical cancer were ELISA positive for HPV-16 VLPs(p$lt;0.01). 2) The positive reactivities for ELISA of HPV-16 VLPs in cervical cancer patients according to clinical characteristics were nor signific antly different. 3) Among women with cervical neoplasia, HPV 16 VLP was positive in 50%(10/20) of HPV-16 positive cases with preinvasive cervical lesion and 72%(50/72) of HPV-16 positive cases with invasive cervical cancer. Conclusion: These results suggest that the considerable number of patients with cervical neoplasia generated an IgG antibody response to the HPV 16 VLPs that can be detected by ELISA. These HPV-16 VLP ELISA may be useful in adjunctive diagnostic asay to HPV-16 DNA test and seroepidemiologic study of HPV-related cervical neopl-asia.

임신성 고혈압과 신생아 호흡곤란증후군

김창이,김수평,이종건,나종구,홍승덕,신종철,김찬주,송경근,조태준 대한산부인과학회 1994 Obstetrics & Gynecology Science Vol.37 No.8

가톨릭의과대학 부속 성모병원에서 1990년 1월 1일부터 1992년 12월 31일 사이에 조기분만한 362명의 신생아(쌍태아 17명)와 345명의 산모의 의무기록을 조사하여 각 임신주수와 혈압, 임신중독증 여부, 24시간 이상된 조기 양막파수, 분만전 출혈여부, 분만전 진통유무, 분만방법, 신생아의 성별, 자궁내 태아의 발육지연 등의 유무에 따른 신생아 호흡곤란 증후군의 발생정도를 Multiple logistic technique을 이용하여 분석 비교한 후에 다음과 같은 결과를 얻었다. 1. 24시간이상 조기양막파수, 그리고 24시간 이상된 질출혈을 조정하였을 때 확장기 혈압이 110이상인 임신성 고혈압군은 정상 혈압군보다 유의하게 높은 신생아 호흡곤란 증후군의 위험도를 나타내었다. 2. 혈압, 24시간이상 조기 양막파수, 24시간 이상 질출혈, 산전분만통의 유무, 신생아의 성별, 자궁내 태아발육지연 등을 조정하였을 때, 임신주수와 분만방법이 신생아 호흡곤란증후군에 영향을 주는 유의한 위험인자로 입증되었다. Hypertension during pregnancy continues to be a major cause of preterm delivery and neonatal morbidity due to RDS. The effect of hypertension in pregnancy on the incidence of neonatal RDS remains controversial. It is due to the fact that the incidence of neonatal RDS was associated with confounding variable such as membrane rupture$gt;24 hours, vaginal bleeding, undergoing labor, having a cesarean section, growth retardation and neonatal sex. In order to investigate the assocation between maternal hypertension and the incidence of neonatal RDS, we used the multiple logistic regression to control for the above mentioned variabled and the 362 preterm birth were retrospectively analyzed. The results were as follows: 1. After adjustment for membrane rupture$gt;24 hours and vaginal bleeding, the risk of developing respiratory distress syndrome was significantly greater(adjusted odds ratio; 2,990, P value=0.002) in babies of hypertensive mothers(diastolic B.P.$gt;110 mmHg). 2. After adjustment for blood pressure, membrane rupture$gt;24 hours, vaginal bleeding, labor, neonatal sex and growth retardation, the risk of developing respiratory distress syndrome was significantly greater (adjusted odds ratio; 1.833, P value=0.04) in babies delivered by cesarean section without labor. These results suggests that the incidence of RDS in babies of hypertensive mothers might be more escalated due to the absence of labor before delivery because of the greater likehood of cesarean section.

자궁경부암 환자에서 혈청내 진단 물질로서 in vitro translated HPV-16 E7 단백질과 GST-fusion HPV-16 E7 단백질의 임상적 효용성 비교

김승조,남궁성은,박종섭,김은주,김찬주,박순희,박동춘,김태연,엄수종 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.7

이상의 결과로서 자궁경부암 환자에서 in vitro translated HPV-16 E7 단백질과 GST-fusion HPV-16 E7 단백질의 임상적 효용성을 비교하여 볼 때 자궁경부암 환자에서 HPV-16 E7 항원에 대한 항체 측정이 질환의 진단을 예측할 수 있는 보조적인 인자로서 도움을 줄 것이며, 특히 in vitro translated HPV-16 E7 단백 항원은 재발의 예측 및 치료 평가에 효과적인 종양표지물질로 이용될 수 있으리라 생각된다. 이와 같이 직접적으로 임상적인 상태를 반영할 수 있는 자궁경부암을 유발시키는 HPV 단백질의 개발 연구와 그들의 임상적인 도입은 자궁경부암의 임상적 진단과 추적 관리에 큰 기여를 할 수 있을 것으로 보이며, 향후 자궁경부암과 연관된 연구에 기본적인 자료로서 가치가 있을 것으로 사료된다. Objective: Recently, a variety of HPV-related proteins have been synthesized and their utility as diagnostic and prognostic markers in cervical cancers is needed. The ability to generate preparative amounts of HPV-16 E7 proteins may have implications for the development of a serologic assay to detect anti-HPV-16 virion immune responses. The purpose of the study is to improve the way of proper management of the cervical cancer by investigating the clinical utility of in vitro translated HPV-16 E7 protein and GST-fusion HPV-16 E7 protein as the serologic marker through comparing the antibody reactions in the sera of the patients. Methods: The serologic responses were investigated in Korean women with cervical neoplasia by radioimmunoprecipitation assay (RIPA) using in vitro translated HPV-16 E7 protein and ELISA using GST-fusion HPV-16 E7 protein. PCR using E6 type-specific primers for HPV-16/18 were used to determine the presence and type of HPV infection (normal controls; 15 cases, preinvasive lesions; 15 cases, and invasive cervical cancers; HPV-16 DNA positive 78 cases and HPV-16 DNA negative 22 cases). Results: The sera of 39% (39/100) of patients with cervical cancer were RIPA positive for in vitro translated HPV-16 E7 protein [HPV-16 DNA positive cases; 41% (32/78), HPV-16 DNA negative cases; 32% (7/22)]. The sera of 29% (29/100) of cervical cancers were ELISA positive for HPV-16 GST-fusion E7 protein [HPV-16 DNA positive cases; 33% (26/78), HPV-16 DNA negative cases; 14% (3/22)]. By the two different methods, 12 cases were positively matched and 32 cases were negatively matched. The positivities for in vitrotranslated HPV-16 E7 protein in the patients with cervical cancer were 14% (7/49) in stage I, 59% (26/44) in stage II, and 86% (6/7) in stage III/IV, by significantly correlating with the advancing stage of the disease (P<0.01). Conclusions: These data suggests that the considerable number of patients with cervical neoplasia generated positive antibody response to in vitro translated protein and GST-fusion protein of HPV-16 E7. In contrast to RIPA method using in vitro translated protein, ELISA method using GST-fusion protein has several advantages for clinical application; use of non-isotope, easy preparation to produce a sufficient of protein, available large scale study. But the positive rates to in vitro translated HPV-16 E7 protein in the patients of cervical cancer were higher in general than those to GST-fusion HPV-16 proteins. Furthermore, the antibody positivities to in vitro translated HPV-16 E7 protein were increased by advancing clinical stage of disease. These HPV-16 E7 proteins might be the disease-specific markers which could be useful in adjunctive diagnostic assay and seroepidemiologic study of HPV-related cervical neoplasia.

고위험 자궁경부암환자에서 Quick Cisplatin-VP16 을 이용한 신보조항암요법의 효과

김승조,김진우,배석년,남궁성은,박종섭,이준모,김찬주,김재훈,박동춘,박용규 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.8

The potential role and determinants of response to a cisplatin-based regimen of neoadju-vant chemotherapy in women with a histologically confirmed first diagnosis of stage IB-Ⅲ cervical cancer were analyzed. From 1993 to 1996, 92 patients with bulky(designated as more than 3×3 cm2 size) mass were treated with cisplatin 60 mg/m2 and etoposide 100 mg/m2, admi-nistered intravenously at 7 day intervals. Seventy cases of radical hysterectomy with pelvic lymph node dissection and 22 cases of radiation therapy were performed 2 to 3 weeks after chemotherapy. At the end of the cycles, the overall clinical response rate of portio was 83.7 %(34.8 % with a complete response and 48.9 % with a partial response). The older ages, lower stages, and squamous cell types correlated favorably with the clinical response of the portio, but neither with the parametrium nor with the vagina. After the operation, we found the diff-erences in histologic responses, with the following parameters:lymphovascular space invasion, 3 mm below stromal invasion and lymph node metastasis. Theses parameters correlated with the clinical responses, and the down-staging of cases were 70 %. In comparison with radiolog-ical findings of pretreatment and postoperative tissue pathology, we could find a decrease in pelvic LN metastasis. The tumor-free survival rate calculated by the Kaplan-Meier product limit method was 75 % but it was 86.1 % for cases without the occurrence of persistent disease after the completion of the treatments. All patients suffered from nausea and vomiting, but grade 4 toxicity was not detected after the routine use of antiemetics. There were no events that delayed the next step in the treatment or caused difficulty during the operation. The results of this study suggest that the neoadjuvant chemotherapy should be accepted as a routine tool in treating high risk cervical cancer in order to improve the likelihood of favorable outcomes.

자궁경부암에서 HPV-16 단백질을 이용한 혈청내 진단물질의 임상적 효용성

김승조,남궁성은,박종섭,김현수,김찬주,박순희,안희경,정근택,박동춘,유왕돈 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.3

Background : Most markers in current clinical use are not cancer-specific, but the ideal tumor marker should be specific for cancer, highly sensitive, clinically practicable, inexpensive, and acceptable to individual. it is still debating that SCCA and CEA are clinically useful for specific tumor markers in management of cervical cancers. Recently, a variety of HPV- related proteins have been synthesized and their utility as diagnostic and prognostic tumor markers in cervical cancers is needed to be assessed by comparing the previous tumor markers ; CEA and SCCA. The early proteins(E6 & E7) of HPV-16 which are responsible for malignant transformation could be constructed by in vitro transcription and translation and the late structural proteins(L1/L2) of HPV-16 have been shown to self-assemble into virus-like particles(VLPs) from baculovirus system when expressed in insect cells. The ability to generate preparative amounts of HPV-16 E6, E7 proteins and L1/L2 VLPs may have implications for the development of a serologic assay to detect anti-HPV-16 virion immune responses to conformational epitopes of HPV-associated cervical neoplasia. Methods : We attempted to investigate serologic response in the sera obtained from Korean women with cervical neoplasia by RIPA(radioimmunoprecipitation assay) using in vitro translated HPV-16 E6, E7 proteins and ELISA using HPV-16 L1/L2 VLPs, PCR method using E6 type-specific primers and probes for HPV-16/18 was used to determine the presence and type of HPV infection in the study population(normal controls ; 15 cases, preinvasive lesions ; 28 patients, and invasive cervical cancers; 124 cases). Result : 1) The sera of 0% of preinvasive lesions and 34%(42/124) of cervical cancers were positive for SCCA and the sera of 0% of preinvasive lesions and 18% (22/124) of cervical cancers were positive for CEA. The positivity of SCCA was increased with advancing clinical stages, but the antibody levels were not correlated with clinical outcome of disease. 2) The sera of 7%(2/28) of preinvasive lesions and 51%(63/124) of cervical cancers were positive for in vitro translated HPV-16 E6 protein(P$lt;0.05) and the sera of 11%(3/28) of preinvasive lesions and 33%(41/124) of cervical cancers were positive for in vitro translated HPV-16 E7 protein(P$lt;0.05). The levels of HPV-16 E6 proteins showed high titers in some invasive cancers, but they didn`t show any fluctuations along with clinical outcomes. In contrast, the antibody levels to HPV-16 E7 protein were correlated to clinical stage and tumor burden in a significant number of cervical cancers. 3) The sera of 7% (1/15) of normal controls, 39%(11/28) of preinvasive lesions and 56% (70/124) of cervical cancers were ELISA positive for HPV-16 L1/L2 VLPs(P$lt;0.05). The positive reactivities for HPV-16 L1/L2 VLPs in cervical cancers by clinical stage, histopathology or HPV DNA types were not significantly different. Conclusion : These results suggest that the considerable number of patients with cervical neoplasia generated positive antibody response to in vitro translated HPV -16 E6, E7 proteins and L1/L2 VLPs. These HPV-16-associated proteins might be disease-specific markers which could be useful in adjunctive diagnostic assay and seroepidemiologic study of HPV-related cervical neoplasia. Especially, the monitoring of antibody to HPV-16 E7 protein seems to be valuable in proper management of cervical cancers for specific tumor marker.

완전포상기태 예후인자로서 접합체형의 임상적 의의

김승조,배석년,신진웅,김찬주,김재훈,이상형,김재동,윤수철 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.10

To evaluate the possible correlation between the origin of complete hydatidiform mole(CHM) and subsequent persistent gestational trophoblastic tumor(GTT) after molar evacuation, we have studied genetic origin patterns against conventional clinical parameters -patient`s age, gestational age, uterine size for gestational age, serum β-hCG levels before molar evacuation- in 69 patients with CHM. In our study, each of large uterine size for gesta-tional age, serum β-hCG levels before molar evacuation, and genetic origin of CHM had a prognostic significance of subsequent persistent GTT. However, each of gestational age and patient`s age is not a good prognostic indicator for subsequent persistent GTT. Among the patients with persistent GTT, there are no differences in clinical parameters- patient`s age, gestational age, tumor age(the interval between evacuation of CHM and initiation of chemotherapy), serum β-hCG levels before molar evacuation and before initiation of chemotherapy- according to the origin of CHM. There are no differences in the analysis of sex-chromosome and variable number tandem repeat sequence YNZ22 and APOB gene in the extracted DNA from frozen tissues and paraffin blocks and from EDTA treated peripheral blood and dried blood specimen on Wartman paper. It is suggested that analysis of sex-chromosome and polymorphism of YNZ22 and APOB gene from the extracted DNA of paraffin block and dried blood specimen on Wartman paper is the valauble experiment to evaluate the origin and the classification of hydatidiform mole and seems to be the sensitive molecular genetic method in predicting subsequent persistent GTT.

자궁경부병변의 진단에서 Hybrid Capture를 이용한 인유두종 바이러스검사법의 효용성

김승조,배석년,남궁성은,박종섭,김찬주,안희경,민옥경,허수영,노승혜,양혜경 대한산부인과학회 1996 Obstetrics & Gynecology Science Vol.39 No.12

Specific HPV types are currently implicated as etiologic agents of precursors and cancerous lesions of the uterine cervix. This study used the data gaine from 350 women who underwent concurrent cervical cytology, colposcopy and HPV DNA test in the Department of Obstetrics & Gynecology, Catholic University Medical College, Kangnam St. Mary`s Hospital from March 1994 to Febrary 1995. Cytologic results showed that 222 patients had normal cytology, 55 patients had ASCUS, 40 patients had LGSIL, 29 had HGSIL, and 4 had cervical cancers. Colposcopy-guided biopsy was done in 149 cases, DNAs extracted from the cervical swabs were analyzed by Hybrid Capture System, of which cervical cells were tested with two pooled probes(probes containig HPV types of low oncogenic risk; 6, 11, 42, 43 and 44 or HPV types of high oncogenic risk; 16, 18, 31, 33, 45, 51, 52 and 56) for HPV detection. The small fraction of DNA from each sample was also analyzed by polymerase chain reaction(PCR) using E6 primers of HPV-16 and HPV-18. Using Hybrid Capture system, detection rates of HPVs with low and high oncogenic risks in each groups showed that the patients with nonspecific cervical lesions was 23.7%(50/211), patients with HPV infection was 31.9%(15/47), CIN-I 66.7%(10/15), CIN-II 62.9%(22/35) and CIN-III 90.5%(38/42). HPVs of high oncogenic risk type were detected in 120 of 350 women(34.3%) by Hybrid Capture system and 180 woman(51.4%) by PCR using HPV E6 primers of HPV-16/18. Prevalence rates of high risk HPVs in CIN-I, CIN-II and CIN-III were 66.7%(10/15), 60% (21/35) and 90.5%(38/42) by Hybrid Capture system and 86.7%(13/15), 74.3%(26/35) and 85.7%(36/42) by PCR, respectively. The detection rates of the two methods were not significantly different in patients with CIN-I, CIN-II and CIN-III(p$gt;0.05). Detection rates of high rsk HPVs inpatients with nonspecific cervical lesions and HPV infection were 19.4% (41/211) and 21.3%(10/47) by Hybrid Capture system, 33.7%(71/211) and 72.3%(34/47) by PCR, respectively. The detectability of HPVs in these lesions by PCR showed better sensitivity than Hybrid Capture System. At each cytology group, the patients who had positie results for high risk HPVs with Hybrid Capture showed higher incidence of CINs than those with negative results(p$lt;0.05). By quantative analysis using Hybrid Capture System, the patients with high viral titer(over the 3.0RLU) in normal cytology had high incidence rate of CINs than Rhose Sith low viral titer. From These results, Hybrid Capture System would be an Ideal method for identifying HPV DNAs especially in low-grade cervical leslons when compairing with PCR method. Also this method provides another information on differentiationg precancerous lesions of cervix into high- or low-risk of progressin. This test might have prognostic value in the management of patients with HPV-Related cervical intrapithelial lesions.

자궁경부 비정상세포진 (ASCUS-LSIL) 의 임상적 의의와 그 평가

김승조,배석년,남궁성은,박종섭,이준모,노덕영,신진웅,김찬주,최은아 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.2

The evaluation of women with low-grade cytologic abnormalities including atypical cells of undetermined significance(ASCUS) and low-grade squamous intraepithelial lesion (LSIL) is a topic of considerable controversy. Some women with low-grade cytologic abnormalities will have high-grade intraepithelial neoplasia(CIN II or III) or even invasive cancer. Now, it is almost universally accepted that the majority of invasive cervical cancer and high-grade intraepithelial neoplasia are associated with Human papillomavirus(HPV). Because of this, there has been increasing tendancy on using another triaging methods for evaluating women with a low grade abnormal Papanicolaou smear. Traditionally colposcopy was used and recently HPV DNA test and cervicography was widely used as a triaging methods. This study used the data gained from 151 evaluable women with ASCUS and LSIL in the Department of Obstetrics & Gynecology, Catholic University Medical College, Kangnam St. Mary`s Hospital from March 1995 to April 1996. 11,401 women had done cytology during this period and result was like this; 10,501 patients had normal cytology(92.1%), 244 patients had ASCUS(2.14%), 35 had AGCUS (atypical glandular cells of undetermined significance: 0.31%), 191 had LSIL(1.68%), 170 had HSIL(1.49%), and 160 had cervical cancers(1.41%). Patients with ASCUS were showed that CIN I WAS 5.6%(4/72), CIN II 4.2%(3/72) and CIN III 15.3%(11/72). Patients with LSIL were showed that CIN I was 5.1%(4/79), CIN II 7.6(6/79), CIN III 15.2%(12/79) and invasive cancer 7.6%(6/79). We adopted three management algorithms for evaluating women with ASCUS and LSIL. Three methods were like this; Colpscopy only or HPV DNA testing using hybrid capture which were used with DNAs extracted from the cerval swabs and tested with two pooled probes(probes containing HPV types of low oncogenic risk; 6, 11, 42, 43 and 44 or HPV types of high oncogenic risk; 16, 18, 31, 33, 35, 45, 51, 52 and 56) for HPV detection or both. We adopted only positive result with high risk HPV-probes in this article. At ASCUS group, sensitivity and specificity were 90.0% ad 32.5% in 62 women with colposcopy and 71.4%, 75% in 28 women with Hybrid Capture System. 27 women with colposcopy and Hybrid Capture System showed that sensitivity was 100%, and specificity was 26.3%. At LSIL group, sensitivity and specificity were 92.6% and 22.7% in 71 women with colposcopy and 69.2%, 65.4% in 39 women with Hybrid Capture System, 37 women with colposcopy and Hybrid Capture System showed that sensitivity was 91.7%, and specificity was 12%. Our result indicate that patients with smears showing some of ASCUS and LSIL are evaluated as CIN I, II, III and even invasive cancer. Therefore as a triage methods, the combination with colposcopy and HPV DNA test in women referred for low-grade abnormal cytology would be used as a sensitive methods for the detection of CINs. However, low -specificity of this combination approach was also considered as problem. This approach provides another information to differentiating ASCUS and LSIL into high- or low-risk group of progression.