자궁경부 원추절제면 양성 관련인자

김병윤,성원준,정근오,이애현,정민지,박일수,이윤순,조영래 대한부인종양 콜포스코피학회 2003 Journal of Gynecologic Oncology Vol.14 No.4

목적 : 원추절제술을 시행할 때 보다 정확하게 병변을 제거하여 원추절제면 양성의 빈도를 낮추기 위하여 절제면 양성에 영향을 줄 수 있는 인자들에 대하여 연구하였다. 연구 방법 : 2002년 1월부터 2003년 6월까지 경북대학교병원 산부인과외래에서 환상투열요법을 이용하여 원추절제술을 시행한 139명의 중증 자궁경부상피내종양(CIN III) 환자들을 대상으로 하여 원추절제면 양성인 환자와 음성인 환자에서 질확대경진 소견과 고위험형 인유두종 바이러스 감염의 정도를 분석하였다. 결과 : 백색상피병변의 색조상태와 병변의 위치가 원추절제면 양성에 통계학적으로 의미있게 영향을 미쳤는데 2등급의 백색상피병변의 색조변화가 있을 때 기타 조건이 동일한 경우 원추절제면에 종양세포가 존재할 위험성이 2배 이상 높았으며 특히 자궁경부상피내종양 병변이 자궁경내막부 위에 존재할 때에 그 위험성은 5배 이상이나 되었다. HPV의 DNA의 양은 원추절제면 상태와 아무런 관계가 없었다. 결론 : 중증 자궁경부상피내종양 환자들을 대상으로 원추절제면 양성에 영향을 줄 수 있는 인자들을 조사한 결과 자궁경부상피내종양 병변의 질확대경진 소견 중 고등급의 백색상피 색조 변화와 특히 자궁경 내막부위에 병변이 위치하는 소견이 있을 때 원추절제면에 종양세포가 존재할 가능성이 매우 높았으며 자궁경부상피내종양의 치료를 위해 원추절제술을 시행할 때 상기한 질확대경진의 소견이 있을때는 원추절제술의 범위를 좀 더 신중하고 충분하게 결정하는 것이 원추절제면 양성의 가능성을 줄이는데 도움이 될 수 있다. Objective : To investigate the variables in association with positive cervical cone margin that is important for predicting residual neoplasia after cervical conizaton in patients with high grade cervical intraepithelial neoplasia. Methods : This study performed retrospective review of abnormal colposcopic findings based on Reid index and high risk HPV viral load by using Hybrid Capture II on 139 patients of CIN III who had undergone cervical conization in outpatient department. Results : In chi-square test, abnormal colposcopic findings of margin, color and lesion location were related to cervical cone margin status. Multivariate logistic regression analysis showed that high grade of acetowhite epithelium (relative risk=2.23, 95% confidence limit=1.003-4.995) and endocervical location of the lesion (relative risk=5.19, 95% confidence limit=2.375-11.320) were significant predictor for cervical cone margin involvement. High risk HPV viral load of the cervical lesion did not affect cone margin status. Conclusion : These data suggest that abnormal colposcopic findings are useful in predicting cervical cone margin status in patients with high grade of cervical intraepithelial lesions and careful reassessment of colposcopy with exact geometry of the conization specimen is necessary before cervical conization.

Burden of cervical neoplasia in mid-western rural Nepal: a population-based study

Niresh Thapa,Girishma Shrestha,Muna Maharjan,Deborah Lindell,Ninu Maskey,Rajiv Shah,Caiyun Ge,Hongbing Cai 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.5

Objective: To assess the burden of cervical neoplasia in mid-western rural, Nepal using cytology, visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI). Method: A cross-sectional, population-based study was conducted. Total of 2,279 married, non-pregnant women aged 20–65 years participated in a screening clinic from May 2016 to January 2017. All eligible women completed self-report of socio-demographic and reproductive health data followed by screening tests. Biopsies were obtained from areas on the cervix assessed by VIA and or VILI to be abnormal. Final disease was confirmed by biopsy report. Results: A total of 96.09% (n=2,190) women were eligible for this study with mean age 32.78±9.33 years. The overall rate of positive cytology, VIA, and VILI were 3.69%, 12.45%, and 16.89%, respectively. Sixty-two cases were biopsy proven cervical neoplasia. Altogether 78 (3.69%) cases were cytologically abnormal: 25 (1.18%) were atypical squamous cells of undetermined significance, 33 (1.56%) were low-grade squamous intraepithelial lesion, 11 (0.52%) were high-grade squamous intraepithelial lesion, and 9 (0.42%) were squamous cell carcinoma. Illiterate women appeared to be at higher risk for cervical neoplasia (p<0.001). Similarly, age ≥46 years (p<0.013), participant's multiple marriages or sexual partners (p<0.005), and positive human immunodeficiency virus status (p<0.001) were significantly associated with abnormal cytology. Conclusion: Based on cytology report, there is 3.69% prevalence of cervical neoplasia among women in a rural region of mid-western, Nepal. A “screen and treat” approach would be more attractive in low resource settings.

Distribution of human papillomavirus type 16 E6 and E7 gene variants in the progression of cervical dysplasia in Korean women

Lee, Chung‐,Won,Bae, Jeong‐,Hoon,Lee, Sung‐,Jong,Ho, Eun‐,Mi,Lee, Il‐,Han,Park, Yong‐,Gyu,Park, Jong‐,Sup Blackwell Publishing Asia 2011 JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH -TO Vol.37 No.10

<P><B>Abstract</B></P><P><B>Aim: </B> This cross‐sectional, hospital‐based study examined the distribution of human papillomavirus 16 E6 and E7 gene variants in Korean women with cervical lesions of varying degrees.</P><P><B>Material & Methods: </B> One hundred and forty‐one Korean women (median age 43 years; range 22–65 years) with human papillomavirus 16 single infections were included. The human papillomavirus 16 E6/E7 sequences were amplified from cytology specimens. The distribution of human papillomavirus 16 variations with respect to cervical lesion was examined by the exact Mantel–Haenszel linear trend test (<I>P</I><SUB>trend</SUB>) and Fisher's exact test (<I>P</I>).</P><P><B>Results: </B> Human papillomavirus 16 E6 and E7 gene variants were identified in a total of 100 women (70.9%). The most prevalent human papillomavirus 16 variants were E6 Thymine178Guanine (number = 70, 49.6%) and E7 Adenine647Guanine (number = 75, 53.2%). Human papillomavirus 16 E6 Thymine178Guanine and E7 Adenine647Guanine were significantly related to the degree of cervical neoplasia (<I>P</I><SUB>trend</SUB> = 0.0002, <I>P</I> < 0.0001; <I>P</I><SUB>trend</SUB> < 0.0001, <I>P</I> < 0.0001, respectively). The odds ratio of human papillomavirus 16 E6 Thymine178Guanine to predict progression to cervical intraepithelial neoplasia 2‐3 and invasive cancer was 2.37 (95% confidence interval 1.03–5.45) and 9.07 (95% confidence interval 2.86–28.72), respectively. The odds ratio of E7 Adenine647Guanine to predict progression to cervical intraepithelial neoplasia 2‐3 and invasive cancer was 3.65 (95% confidence interval 1.16–8.51) and 9.07 (95% confidence interval 2.86–28.72), respectively.</P><P><B>Conclusion: </B> The distribution of HPV variants appears to be related to geographic difference. Human papillomavirus 16 E6 Thymine178Guanine and E7 Adenine647Guanine can be used as the candidate marker for the progression of the cervical neoplasia.</P>

자궁경부종양의 진단 및 치료적 원추절제술에 대한 임상적 고찰

윤만수 부산대학교 병원 암연구소 2006 부산대병원학술지 Vol.- No.20

Purpose : To evaluate clinical efficacy of diagnosis and treatment using knife conization for cervical intraepithelial neoplasia. Subject and Methods : We have treated 50 women, then were divided into diagnostic and therapeutic conization group and then indication of conization, cytology, directed biopsy, cone margin and residual lesion of each group were compared respectively. Results Diagnostic conization was performed in 22 patients who were upper limit of the lesion was invisible, squamocolumnar junction was not seen, High-grade squamous intraepithelial lesions or invasive cancer was suspected. four cases of follow-up group had negative cone margin and no recurrence. Eighteen cases of positive cone margin were performed repeat conization and immediate total abdominal hysterectomy. There was no recurrence after repeat conization and hysterectomy. Therapeutic conization was performed in such 28 cases as upper limit of the lesion was visible, squamocolumnar junction was seen and invasive cancer was ruled out. Twentyfive cases of therapeutic conization group had negative cone margin and were follow up. Three cases of positive cone margin were performed repeat conization and were follow up. There was no recurrence after repeat conization. Conclusions : The knife conization was useful to detect· unexpected invasive cervical cancer and revealed excellent therapuetic & diagnostic effects for cervical intraepithelial neoplasia. Careful follow up was needed after knife conization of cervical intraepithelial neoplasia because of the possibile residual disease even though histologic proven negative cone margin.

Efficacy of loop electrosurgical excision procedure with cold coagulation for treating cervical intraepithelial neoplasia: A two center cohort study

( Hee Seung Kim ),( Jeong Eun Kwon ),( Jeong Ha Kim ),( Anna Kim ),( Na Ra Lee ),( Miseon Kim ),( Maria Lee ),( Dong Hoon Suh ),( Yong Beom Kim ) 대한산부인과학회 2017 Obstetrics & Gynecology Science Vol.60 No.2

Objective To evaluate the efficacy of loop electrosurgical excision procedure (LEEP) combined with cold coagulation for treating cervical intraepithelial neoplasia (CIN). Methods We reviewed clinic-pathologic data of 498 patients treated with LEEP alone (n=354), and LEEP combined with cold coagulation (n=144) between January 2000 and December 2011. After LEEP, we followed up all patients by using Papanicolaou smear and human papillomavirus (HPV) test, and evaluated abnormal cervical cytology-free interval and high-risk HPV infection-free interval. Moreover, we investigated independent factors affecting abnormal cervical cytology or high-risk HPV infection after LEEP. Results Abnormal cervical cytology-free interval was longer in patients treated with LEEP combined with cold coagulation than in those treated with LEEP alone (mean, 92.4 vs. 84.4 months; P=0.01), and patients treated with LEEP combined with cold coagulation also showed longer high-risk HPV infection-free interval than those treated with LEEP alone (mean, 87.6 vs. 59.1 months; P=0.01). Moreover, CIN 3 and cold coagulation were factors affecting abnormal cervical cytology after LEEP (adjusted hazard ratios, 1.90 and 0.61; 95% confidence intervals, 1.27 to 2.84 and 0.39 to 0.96), and CIN 3, positive deep cervical margin and cold coagulation were also factors affecting high-risk HPV infection after LEEP (adjusted hazard ratios, 2.07, 4.11, and 0.64; 95% confidence intervals, 1.38 to 3.08, 1.63 to 10.39, and 0.43 to 0.96). When we performed subgroup analyses for patients with CIN 2 or CIN 3, the result were similar. Conclusion LEEP combined with cold coagulation may be more effective for treating CIN than LEEP alone. Moreover, cold coagulation may decrease the risk of potential of recurrence after LEEP.

자궁경부의 Human papillomavirus감염 :상피내종양과의 상관성에 대한 면역조직화학적 및 세포학적 연구

김미진,최원희,이태숙 대한병리학회 1989 Journal of Pathology and Translational Medicine Vol.23 No.2

Combined effect of diet and cervical microbiome on the risk of cervical intraepithelial neoplasia

Seo, S.S.,Oh, H.Y.,Lee, J.K.,Kong, J.S.,Lee, D.O.,Kim, M.K. Churchill Livingstone 2016 Clinical nutrition Vol.35 No.6

Background & aims: Several food groups or dietary factors and the cervical microbiota may be involved in cervical carcinogenesis, but the evidence is not clear yet. We aimed to assess the association between dietary pattern and cervical intraepithelial neoplasia (CIN) and the combined effect of dietary pattern and cervical microbiome on the risk of CIN. Methods: The cervical microbiota and diet assessed by pyrosequencing and a food-frequency questionnaire, respectively, of 65 women with CIN and 72 control women were used in this study. Principal component analysis and cluster analysis were used to identify dietary patterns and microbiome community types, respectively. The association between dietary pattern and CIN risk was assessed using multivariable logistic regression analysis. The combined effect of dietary pattern and microbiome on CIN risk was determined using relative excess risk due to interaction (RERI) and synergy index (S). Results: Two dietary patterns and four community types were identified: prudent diet characterized by higher intake of vegetables and fishes; semi-Western diet characterized by higher intake of bread, dairy products, eggs, and soft drinks and relatively higher fat intake ratio; and Lactobacillus crispatus-, L. iners-, Atopobium vaginae-, and Prevotella bivia-dominant types. The high-scoring group of participants with a semi-Western diet had a higher risk of CIN (odds ratio [OR] 3.44, 95% confidence interval [CI] 1.11-10.7, p = 0.03), compared with the low or medium-scoring group of those with a semi-Western diet. L. iners-dominant (OR 6.39, 95% CI 1.52-26.7, p = 0.01) and A. vaginae-dominant (OR 4.99, 95% CI 1.17-21.3, p = 0.03) dominant types had a higher risk of CIN, compared with the L. crispatus-dominant type. The synergistic effect of semi-Western diet and A. vaginae-dominant type on CIN risk was observed (OR 20.8, 95% CI 2.21-195.6, p = 0.01, RERI/S 9.64/1.96). Conclusions: Our findings suggest that semi-Western diet and its combination with A. vaginae-dominant microflora may represent an important risk factor for cervical neoplasia.

자궁경부상피내종양의 원추절제술 후 절제 변연부 상태에 영향을 미치는 인자 분석

정차남 ( Cha Nam Jung ),오나정 ( Na Jung Oh ),류기영 ( Ki Young Ryu ),오화은 ( Hwa Eun Oh ),김우영 ( Woo Young Kim ) 대한산부인과학회 2011 Obstetrics & Gynecology Science Vol.54 No.12

목적 자궁경부 원추절제술 후 절제 변연부 침범 소견을 보일 때 병변의 중증도가 이에 미치는 영향에 대하여 살펴보고 절제 변연부 침범과 재발 및 잔류종양의 연관성에 대하여 알아보고자 하였다. 연구방법 2003년 11월부터 2011년 2월까지 자궁경부 원추절제술을 시행 받은 후 cervical intraepithelial neoplasia (CIN)으로 진단된 환자 202명을 대상으로 후향적 연구를 시행하였다. 원추절제술 후 환자는 자궁절제술을 시행 받거나 3-6개월 간격으로 자궁경부세포검사를 통한 추적관찰을 시행하였으며 이상 소견을 보이는 경우 질확대경하에 조직검사를 시행하였다. 재발은 CIN I 이상의 조직 소견을 보이는 경우로 정의하였다. 결과 CIN으로 진단된 환자 202명 중 CIN I은 46명(22.8%), CIN II는 35명(17.3%), CIN III는121명(59.9%)이었다. 절제 변연부 침범 소견을 보인 환자는 67명(33.2%)이었고 CIN I은 7명(10.4%), CIN II는 14명(20.9%), CIN III는 46명(68.7%)으로 CIN의 중증도가 심할수록 절제 변연부의 침범 빈도가 증가하였다(P = 0.009). 자궁절제술을 시행 받은 환자는 28명(13.9%)으로 절제 변연부 침범이 없었던 환자는 13명, 절제 변연부 침범이 있었던 환자는 15명이었고 각각 7명(53.8%)과 5명(33.3%)에서 잔류 병변이 존재하여 절제 변연부의 침범 여부와 잔류종양의 유무는 통계학적으로 유의한 상관관계를 보이지 않았다(P = 0.445). 보존적 치료를 시행한 환자는 174명으로 이 중 절제 변연부 침범을 보인 3명(3/52, 5.7%)과 절제 변연부 침범을 보이지 않은 2명(2/122, 1.6%)의 환자에서만 재발을 보였다(P = 0.335). 결론 CIN 환자에 있어 병변의 중등도가 심할수록 절제 변연부 침범이 있을 가능성이 크지만 절제 변연부의 침범이 있다 하더라도 실제적으로 잔류 병변이 없는 경우가 더 많으며 절제 변연부의 침범 여부가 재발과는 유의한 상관관계가 없는 것으로 나타났다. 따라서 변연부 침범소견을 보이는 경우라도 지속적 추적관찰만 잘 이루어 질 수 있다면 CIN의 치료로 충분하다 할 수 있겠다. 또한 절제 변연부의 침범이 없는 경우에도 잔류종양이 남아 있을 가능성이 있으므로 주의 깊은 추적관찰이 필요할 것으로 생각된다. Objective The aim of this study was to evaluate the correlation between resection margin status after conization and severity of dysplasia and to evaluate the risk of residual disease and recurrence for positive resection margin after conization. Methods We retrospectively reviewed the medical and histopathological records of 202 patients who underwent conization that revealed cervical intraepithelial neoplasia (CIN) at Myongji Hospital, Kwandong University College of Medicine between November 2003 and February 2011. Patients were followed up every three to six months with cervicovaginal smears, and suspected cases of recurrence were subjected to colposcopy and biopsy. Results A total of 202 patients underwent conization (46 [22.8%] with CIN I, 35 [17.3%] with CIN II, 121 [59.9%] with CIN III) and were enrolled this study. The cone resection margin involved in 33.2% (67/202) of the patients (7/67 [10.4%] with CIN I, 14/67 [20.9%] with CIN II, 46/67 [68.7%] with CIN III). The frequency of resection margin involvement after conization was higher with increasing severity of CIN (P = 0.009). Hysterectomy was performed in 28 patients (13.9%). The incidence of residual disease was 53.8% (7/13) in resection margin free group and 33.3% (5/15) in resection margin involvement group (P = 0.445). There were three (3/52, 5.7%) recurrence in resection margin involvement group and two (2/122, 1.6%) recurrence in resection margin free group (P = 0.335). Conclusion The risk of resection margin involvement after conization increased with increasing severity of CIN. However, the women with involvement of resection margin after conization often have no residual disease and there was no difference in recurrence between the resection margin status. Therefore, patients whose resection margins were involved after conization could be managed conservatively.

Clinical Implication of p16, Ki-67, and Proliferating Cell Nuclear Antigen Expression in Cervical Neoplasia: Improvement of Diagnostic Accuracy for High-grade Squamous Intraepithelial Lesion and Prediction of Resection Margin Involvement on Conization Sp

김태현,한지혜,신은,노재홍,김희승,송용상 대한암예방학회 2015 Journal of cancer prevention Vol.20 No.1

Background:Cervical intraepithelial neoplasia (CIN) grading is subjective and affected by substantial rates of discordance among pathologists. Although the use of p16INK4a (p16) staining has beenproven to improve diagnostic accuracy for high-grade squamous intraepithelial lesion (HSIL), the clinical evidence for use of Ki-67 and proliferating cell nuclear antigen (PCNA) is insufficient to make an independent recommendation for use, alone or in combination. The primary objective was to evaluate clinical utility of Ki-67and PCNA in combination with p16 in diagnosing HSIL. Also, we assessed the correlation between expressions of three biomarkers and resection margin status of conization specimen. Methods:The expressions of p16, Ki-67, and PCNA were evaluated by immunohistochemical methods in 149 cervical tissues encompassing 17 negative lesion, 31 CIN 1, 25 CIN 2, 41 CIN 3, and 35 invasive squamous cell carcinoma. The immunohistochemical staining results were classified into four grades: 0, 1+, 2+ and 3+. Results:The expression of three biomarkers was positively associated with CIN grade. Ki-67 immunostaining did not increase the accuracy of HSIL diagnosis when combined with p16 immunostaining compared with p16 immunostaining alone. In contrast, combining the staining results for p16 and PCNA (p16 = 3+ and PCNA ≥2+) increased its specificity (66.7% vs. 75.0%, P= 0.031) without decrease of its sensitivity (98.7% vs. 98.7%) for diagnosis of CIN 3 and more sever lesion. Subgroup analysis for conization specimen with CIN 2 and CIN 3 showed that positive Ki-67 immunostaining was an independent risk factor for predicting resection margin positivity(odds ratio = 6.52, 95% confidence interval 1.07-39.64). Conclusions:We found that the combined use of p16 and PCNA immunostaining enhanced diagnostic accuracy for HSIL. Positive Ki-67 immunostaining was associated with incomplete excision

p16INK4a immunohistochemistry is a promising biomarker to predict the outcome of low grade cervical intraepithelial neoplasia: comparison study with HPV genotyping

Sakiko Nishio,Takuma Fujii,Hiroshi Nishio,Kaori Kameyama,Miyuki Saito,Takashi Iwata,Kaneyuki Kubushiro,Daisuke Aoki 대한부인종양학회 2013 Journal of Gynecologic Oncology Vol.24 No.3

Objective: In cervical intraepithelial neoplasia (CIN), p16INK4a immunohistochemistry has been reported to be a useful diagnostic biomarker. However, limited information is available about the association between the p16INK4a immunohistochemistry and the outcomes of CIN. Here, we report p16INK4a immunohistochemistry as an effective biomarker to predict the outcomes of CIN. Methods: p16INK4a immunohistochemistry was performed in patients with CIN from January 2000 to August 2009. Among these patients, we have performed a retrospective analysis of the medical records to evaluate the outcome of CIN 1-2 and performed statistical analysis to determine the correlation between p16INK4a expression and the outcomes. We also performed HPV genotyping and analyzed the relation between the infecting human papillomavirus (HPV) genotype and the outcomes. Results: A total of 244 patients, including 82 with CIN 1, 60 with CIN 2, and 102 with CIN 3, were examined. The rate of p16INK4a overexpression increased with increasing CIN grade, 20.7% for CIN 1, 80.0% for CIN 2, and 89.2% for CIN 3, with significant differences between CIN 1 and CIN 2-3 group. In the 131 CIN 1-2 patients, the progression rate was significantly higher for the patients showing p16INK4a overexpression than for those not showing p16INK4a overexpression (p=0.005); the regression rate was also found to be significantly lower for the patients showing p16INK4a overexpression (p=0.003). High-risk HPV genotypes were detected in 73 patients (73.7%). Both progression and regression rates were not significantly different between the high-risk HPV-positive and HPV-negative groups (p=0.401 and p=0.381, respectively). Conclusion: p16INK4a overexpression was correlated with the outcome of CIN 1-2, and p16INK4a is considered to be a superior biomarker for predicting the outcome of CIN 1-2 compared with HPV genotyping.