今日の臨床サポート

子宮頸部上皮内腫瘍(CIN)

著者: 藤井恒夫 医療法人 藤井レディースクリニック

監修: 青木大輔 慶應義塾大学医学部産婦人科学教室

著者校正/監修レビュー済:2020/08/06
参考ガイドライン:
  1. 日本産科婦人科学会・日本産婦人科医会 共同編集:産婦人科診療ガイドライン 婦人科外来編2020
患者向け説明資料

概要・推奨   

  1. 組織診で確認されたCIN1は6カ月ごとに細胞診とコルポスコピーでフォローする(推奨度2)。
  1. 組織診で確認されたCIN1はHPVタイピング検査を用いた管理を行うことができる(推奨度2)。
  1. 組織診で確認されたCIN2は3~6カ月ごとに細胞診とコルポスコピーを併用して厳重なフォローをする(推奨度2)。
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
藤井恒夫 : 特に申告事項無し[2021年]
監修:青木大輔 : 講演料(アストラゼネカ株式会社,武田薬品工業株式会社,中外製薬株式会社),研究費・助成金など(アストラゼネカ株式会社,中外製薬株式会社,インサイト・バイオサイエンシズ・ジャパン合同会社)[2021年]

改定のポイント:
  1. 最新の産婦人科診療ガイドライン 婦人科外来編2020 に基づき、確認を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 子宮頸部上皮内腫瘍(cervical intraepithelial neoplasia、CIN)は、1966年にR.M.Richartにより子宮頸部の異形成~上皮内癌を連続した病変と捉える考え方からつけられた名称で、分化傾向の乏しい未熟細胞が重層扁平上皮の基底膜から表層に向かって広がる程度によりCIN1/2/3と3段階に分類される[1]。CIN1は軽度異形成、CIN2は中等度異形成、CIN3は高度異形成~上皮内癌に相当する。
 
子宮頸部正常扁平上皮とCINの組織像

CINは分化傾向の乏しい未熟細胞が重層扁平上皮の基底膜から表層に向かって広がる程度によりCIN1、CIN2、CIN3の3段階に分かれる。
a:Normal
b:CIN1
c:CIN2
d:CIN3

 
  1. CINは、ヒトパピローマウイルス(human papillomavirus、HPV)の感染が密接に関与しており、CIN1はHPV感染の組織像、CIN2はHPV感染の範疇と腫瘍性変化を伴った細胞が混在した組織像、CIN3はHPV感染細胞が腫瘍細胞に移行し置換された組織像と考えてよい。
  1. 子宮頸部の扁平上皮系前癌病変は、異形成、CINの3段階分類のほかに、臨床上の取り扱い(経過観察/治療)により2段階に分ける扁平上皮内病変(squamous intraepithelial lesion、SIL)の分類がある。LSIL(low grade SIL)はCIN1、HSIL(high grade SIL)はCIN2~CIN3に相当する。子宮頸癌取扱い規約 病理編 第4版(2017年)はSILとCINの併記を採用している(例:LSIL/CIN1、HSIL/CIN2、HSIL/CIN3)。
 
CINの分類

扁平上皮系前癌病変は、異形成、CIN、SILの3種類に分類される。

 
  1. CINは数年から十数年で浸潤癌に進展する。CINのgradeが高いほど浸潤癌に進展する(CIN1は1%、CIN2は5%、CIN3は>12%)[2]
  1. 組織診で確認されたCIN1は6カ月ごとに細胞診とコルポスコピーでフォローする。
  1. 組織診で確認されたCIN2は3~6カ月ごとに細胞診とコルポスコピーを併用して厳重なフォローをする。
  1. CIN1/2の進展リスク評価のためにHPVタイピング検査を行うことができる。その場合、HPV16、18、31、33、35、45、52、58のいずれかが陽性の病変では進展リスクが高いので、それ以外のHPV陽性例あるいはHPV陰性例とは分けて管理することが勧められる[3]
  1. CIN2は妊娠女性を除き、フォローで自然消退しない場合、本人の強い希望がある場合、継続的な受診が困難な場合やHPVタイピング検査でHPV16、18、31、33、35、45、52、58のいずれかが陽性の症例は選択的に治療することができる[3]
  1. 組織診で確認されたCIN3は治療する。
  1. 妊婦のCINはフォローアップが原則で、どうしても浸潤癌が否定できない場合のみ診断的子宮頸部円錐切除が許される。
  1. 妊婦のCIN3は細胞診、コルポスコピー、生検組織診で微小浸潤癌以上の病変の疑いのない場合は、分娩後まで円錐切除を延期することが可能である。
  1. 妊婦のCIN3は、細胞診、コルポスコピー、生検組織診で微小浸潤癌以上の病変の疑いのある場合は円錐切除術が必要である。
問診・診察のポイント  
問診:
  1. CINの既往を確認する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: R M Richart
雑誌名: Cancer. 1966 Nov;19(11):1635-8.
Abstract/Text
PMID 5925272  Cancer. 1966 Nov;19(11):1635-8.
著者: A G Ostör
雑誌名: Int J Gynecol Pathol. 1993 Apr;12(2):186-92.
Abstract/Text The literature dealing with the natural history of cervical intraepithelial neoplasia (CIN) since 1950 is reviewed, in particular from the viewpoint of regression, persistence, and progression. When stratified into the various grades of severity, the composite data indicate the approximate likelihood of regression of CIN 1 is 60%, persistence 30%, progression to CIN 3 10%, and progression to invasion 1%. The corresponding approximations for CIN 2 are 40%, 40%, 20%, and 5%, respectively. The likelihood of CIN 3 regressing is 33% and progressing to invasion greater than 12%. It is obvious from the above figures that the probability of an atypical epithelium becoming invasive increases with the severity of the atypia, but does not occur in every case. Even the higher degrees of atypia may regress in a significant proportion of cases. As morphology by itself does not predict which lesion will progress or regress, future efforts should seek factors other than morphological to determine the prognosis in individual patients.

PMID 8463044  Int J Gynecol Pathol. 1993 Apr;12(2):186-92.
著者: Anna-Barbara Moscicki, Stephen Shiboski, Nancy K Hills, Kimberly J Powell, Naomi Jay, Evelyn N Hanson, Susanna Miller, K Lisa Canjura-Clayton, Sepidah Farhat, Jeanette M Broering, Teresa M Darragh
雑誌名: Lancet. 2004 Nov 6-12;364(9446):1678-83. doi: 10.1016/S0140-6736(04)17354-6.
Abstract/Text BACKGROUND: The aim of this study was to assess the probability of low-grade squamous intra-epithelial lesion (LSIL) regression in young women, and to examine the factors associated with this regression.
METHODS: In a longitudinal study of human papilloma virus (HPV) infection, female adolescents aged 13-22 years were examined every 4 months by cytology, colposcopy, and HPV DNA status. Both prevalent and incident LSIL cases were included in the analysis, with regression defined as at least three consecutive normal Pap smears.
FINDINGS: Median follow-up time from baseline (defined as the time of first LSIL diagnosis) for the 187 women with LSIL was 61 months (IQR 34-80). Median time they had been sexually active at diagnosis was 3.2 years (2.6-6.5). Probability of regression for the entire cohort was 61% (95% CI 53-70) at 12 months and 91% (84-99) at 36 months of follow-up. No associations were found between LSIL regression and HPV status at baseline, sexual behaviour, contraceptive use, substance or cigarette use, incident sexually transmitted infection, or biopsy. Multivariate analysis showed that only HPV status at the current visit was associated with rate of regression, whether infection was caused by one or more viral types (relative hazard=0.3 [95% CI 0.21-0.42], and 0.14 [0.08-0.25], respectively).
INTERPRETATION: The high rate of regression recorded in this study lends support to observation by cytology in the management of LSIL in female adolescents. Negative HPV status was associated with regression, suggesting that HPV testing could be helpful in monitoring LSIL.

PMID 15530628  Lancet. 2004 Nov 6-12;364(9446):1678-83. doi: 10.1016/S・・・
著者: Koji Matsumoto, Akinori Oki, Reiko Furuta, Hiroo Maeda, Toshiharu Yasugi, Naoyoshi Takatsuka, Akira Mitsuhashi, Takuma Fujii, Yasuo Hirai, Tsuyoshi Iwasaka, Nobuo Yaegashi, Yoh Watanabe, Yutaka Nagai, Tomoyuki Kitagawa, Hiroyuki Yoshikawa, Japan HPV And Cervical Cancer Study Group
雑誌名: Int J Cancer. 2011 Jun 15;128(12):2898-910. doi: 10.1002/ijc.25630. Epub 2010 Oct 13.
Abstract/Text Only a subset of cervical precursor lesions progress to cervical cancer and because of the lack of the predictive markers, it cannot be ascertained which lesions will progress or not. To estimate the risk of disease progression associated with human papillomavirus (HPV) genotypes, we followed 570 Japanese women with cytological LSIL (low-grade squamous intraepithelial lesion) and histological CIN (cervical intraepithelial neoplasia) grade 1-2 lesions (479 CIN 1; 91 CIN 2) at 3 to 4 month intervals for a mean follow-up period of 39.1 months. At entry, we detected HPV DNA in cervical samples by polymerase chain reaction-based methodology. Over the period of follow-up period, 46 lesions progressed to CIN 3 while 362 regressed to normal cytology. Women with multiple HPV infections were more likely to have persistent lesions (hazard ratio [HR] for regression, 0.65; 95% confidence interval [CI], 0.42-1.02; p = 0.07); however, multiple infections did not increase the risk of progression (HR for progression, 1.04; 95% CI, 0.37-2.94; p = 0.94). After adjusting for CIN grade and women's age, HRs for progression to CIN 3 (vs. women with low-risk types or negative for HPV DNA) varied markedly by HPV genotype: type 16 (11.1, 95% CI: 1.39-88.3); 18 (14.1, 0.65-306); 31 (24.7, 2.51-243); 33 (20.3, 1.78-231); 35 (13.7, 0.75-251); 52 (11.6, 1.45-93.3); 58 (8.85, 1.01-77.6); other high-risk types (4.04, 0.47-34.7). HPV 45 was not detected in our study subjects. The cumulative probability of CIN 3 within 5 years was 20.5% for HPV 16, 18, 31, 33, 35, 52 and 58; 6.0% for other high-risk types; 1.7% for low-risk types (p = 0.0001). In conclusion, type-specific HPV testing for women with LSIL/CIN 1-2 lesions is useful for identifying populations at increased or decreased risk of disease progression.

Copyright © 2010 UICC.
PMID 20734388  Int J Cancer. 2011 Jun 15;128(12):2898-910. doi: 10.100・・・
著者: M Kyrgiou, G Koliopoulos, P Martin-Hirsch, M Arbyn, W Prendiville, E Paraskevaidis
雑誌名: Lancet. 2006 Feb 11;367(9509):489-98. doi: 10.1016/S0140-6736(06)68181-6.
Abstract/Text BACKGROUND: Conservative methods to treat cervical intraepithelial neoplasia and microinvasive cervical cancer are commonly used in young women because of the advent of effective screening programmes. In a meta-analysis, we investigated the effect of these procedures on subsequent fertility and pregnancy outcomes.
METHODS: We searched for studies in MEDLINE and EMBASE and classified them by the conservative method used and the outcome measure studied regarding both fertility and pregnancy. Pooled relative risks and 95% CIs were calculated with a random-effects model and interstudy heterogeneity was assessed with Cochrane's Q test.
FINDINGS: We identified 27 studies. Cold knife conisation was significantly associated with preterm delivery (<37 weeks; relative risk 2.59, 95% CI 1.80-3.72, 100/704 [14%] vs 1494/27 674 [5%]), low birthweight (<2500 g; 2.53, 1.19-5.36, 32/261 [12%] vs 905/13 229 [7%]), and caesarean section (3.17, 1.07-9.40, 31/350 [9%] vs 22/670 [3%]). Large loop excision of the transformation zone (LLETZ) was also significantly associated with preterm delivery (1.70, 1.24-2.35, 156/1402 [11%] vs 120/1739 [7%]), low birthweight (1.82, 1.09-3.06, 77/996 [8%] vs 49/1192 [4%]), and premature rupture of the membranes (2.69, 1.62-4.46, 48/905 [5%] vs 22/1038 [2%]). Similar but marginally non-significant adverse effects were recorded for laser conisation (preterm delivery 1.71, 0.93-3.14). We did not detect significantly increased risks for obstetric outcomes after laser ablation. Although severe outcomes such as admission to a neonatal intensive care unit or perinatal mortality showed adverse trends, these changes were not significant.
INTERPRETATION: All the excisional procedures to treat cervical intraepithelial neoplasia present similar pregnancy-related morbidity without apparent neonatal morbidity. Caution in the treatment of young women with mild cervical abnormalities should be recommended. Clinicians now have the evidence base to counsel women appropriately.

PMID 16473126  Lancet. 2006 Feb 11;367(9509):489-98. doi: 10.1016/S014・・・
著者: Nicolas F Schlecht, Robert W Platt, Eliane Duarte-Franco, Maria C Costa, João P Sobrinho, José C M Prado, Alex Ferenczy, Thomas E Rohan, Luisa L Villa, Eduardo L Franco
雑誌名: J Natl Cancer Inst. 2003 Sep 3;95(17):1336-43.
Abstract/Text BACKGROUND: Little is known about the duration of precancerous cervical lesions in relation to human papillomavirus (HPV) infection. We estimated rates of progression and regression and sojourn times of cervical squamous intraepithelial lesions (SILs) according to HPV status.
METHODS: We used data from a longitudinal study of HPV infection and cervical neoplasia in São Paulo, Brazil. Cervical specimens were taken from 2404 women for Pap cytology and polymerase chain reaction-based HPV testing every 4-6 months over a period of 8 years. We used actuarial and non-actuarial analyses to measure time to and rates of lesion progression and regression according to status and type of HPV infection.
RESULTS: During follow-up, 118 low-grade SIL (LSIL), 24 high-grade SIL (HSIL), and 173 atypical squamous cells of undetermined significance (ASCUS) events were detected. Mean time to progression from ASCUS to LSIL or worse and from LSIL to HSIL or worse was shorter in women with oncogenic HPV types than in women with no HPV infection (mean times for ASCUS progression were 67.0 and 88.0 months, respectively, in women with oncogenic HPV and no HPV, difference = 21.0 months, 95% confidence interval [CI] = 11.3 to 30.7 months; mean times for LSIL progression were 73.3 and 83.5 months, respectively, difference = 10.2 months, 95% CI = -0.15 to 20.6 months). Half of the LSILs regressed to normal or ASCUS within 6 months. Mean times for regression from ASCUS to normal, from LSIL to ASCUS or normal, and from HSIL/cervical intraepithelial neoplasia 2 to ASCUS or normal were longer for women with oncogenic HPV types (16.8 months, 95% CI = 7.5 to 26.2 months; 13.8 months, 95% CI = 8.8 to 18.7 months; and 17.1 months, 95% CI = 4.1 to 30.1 months, respectively) than for women with non-oncogenic HPV types (7.7 months, 95% CI = 5.2 to 10.2 months; 7.8 months, 95% CI = 5.3 to 10.2 months; 8.9 months, 95% CI = 3.3 to 14.6 months) or for women with no HPV infection (7.6 months, 95% CI = 6.9 to 8.4 months; 7.6 months, 95% CI = 6.4 to 8.7 months; and 7.0 months, 95% CI = 5.0 to 8.9 months, respectively).
CONCLUSION: Precursor lesions of the cervix persist longer and progress more quickly in women with oncogenic HPV infections than in women with non-oncogenic infections or without HPV. Testing cervical lesions for oncogenic HPVs may help identify those that are likely to progress rapidly.

PMID 12953088  J Natl Cancer Inst. 2003 Sep 3;95(17):1336-43.
著者: P Holowaty, A B Miller, T Rohan, T To
雑誌名: J Natl Cancer Inst. 1999 Feb 3;91(3):252-8.
Abstract/Text BACKGROUND: A historical cohort of Toronto (Ontario, Canada) women whose Pap smear histories were recorded at a major cytopathology laboratory provided the opportunity to study progression and regression of cervical dysplasia in an era (1962-1980) during which cervical squamous lesions were managed conservatively.
METHODS: Actuarial and Cox's survival analyses were used to estimate the rates and relative risks of progression and regression of mild (cervical intraepithelial neoplasia 1 [CIN1]) and moderate (CIN2) dysplasias. In addition, more than 17,000 women with a history of Pap smears between 1970 and 1980 inclusive and who were diagnosed as having mild, moderate, or severe dysplasia were linked to the Ontario Cancer Registry for the outcome of any subsequent cervical cancers occurring through 1989.
RESULTS: Both mild and moderate dysplasias were more likely to regress than to progress. The risk of progression from mild to severe dysplasia or worse was only 1% per year, but the risk of progression from moderate dysplasia was 16% within 2 years and 25% within 5 years. Most of the excess risk of cervical cancer for severe and moderate dysplasias occurred within 2 years of the initial dysplastic smear. After 2 years, in comparison with mild dysplasia, the relative risks for progression from severe or moderate dysplasia to cervical cancer in situ or worse was 4.2 (95% confidence interval [CI] = 3.0-5.7) and 2.5 (95% CI = 2.2-3.0), respectively.
CONCLUSION: The risk of progression for moderate dysplasia was intermediate between the risks for mild and severe dysplasia; thus, the moderate category may represent a clinically useful distinction. The majority of untreated mild dysplasias were recorded as regressing to yield a normal smear within 2 years.

PMID 10037103  J Natl Cancer Inst. 1999 Feb 3;91(3):252-8.
著者: J Melnikow, J Nuovo, A R Willan, B K Chan, L P Howell
雑誌名: Obstet Gynecol. 1998 Oct;92(4 Pt 2):727-35.
Abstract/Text OBJECTIVE: To define the strengths and weaknesses of existing research on the natural history of cervical squamous intraepithelial lesions (SIL) and to estimate rates of progression and regression without treatment.
DATA SOURCES: Studies of women whose cervical smears showed squamous atypia or worse and who were observed for a minimum of 6 months were identified by a search of MEDLINE from 1966 to 1996, Current Contents, the Federal Research in Progress database, and references of review articles and identified studies, and by experts in the field.
METHODS OF STUDY SELECTION: Fifteen of 81 studies were eligible for data extraction. To be eligible, studies had to report a minimum of 6 months' follow-up without treatment; relate entry cytologic findings to outcomes; and report entry cytologic findings so that the study population could be stratified into categories of atypical cells of undetermined significance (ASCUS), low-grade SIL, or high-grade SIL. Studies published before 1970 were excluded.
TABULATION, INTEGRATION, AND RESULTS: Eligible studies, representing 27,929 patients, were stratified according to entry cytologic findings. The following rates of progression to high-grade SIL at 24 months were found: ASCUS, 7.13% (95% confidence interval [CI] 0.8%, 13.5%); low-grade SIL, 20.81% (6.08%, 35.55%); and high-grade SIL, 23.37% (12.82%, 32.92%). The following rates of invasive cancer at 24 months were found: ASCUS, 0.25% (0%, 2.25%); low-grade SIL, 0.15% (0%, 0.71%); and high-grade SIL, 1.44% (0%, 3.95%). The following rates of regression to normal were found: ASCUS, 68.19% (57.51%, 78.86%); low-grade SIL, 47.39% (35.92%, 58.86%); and high-grade SIL, 35.03% (16.57%, 53.49%). Study heterogeneity was not explained by regression analysis of study level variables.
CONCLUSION: Our findings for borderline and low-grade abnormal cervical cytologic results suggest a relatively low risk of invasive cervical cancer with observation up to 24 months and support the clinical policy of early colposcopy for high-grade lesions.

PMID 9764690  Obstet Gynecol. 1998 Oct;92(4 Pt 2):727-35.
著者: N P Yost, J T Santoso, D D McIntire, F A Iliya
雑誌名: Obstet Gynecol. 1999 Mar;93(3):359-62.
Abstract/Text OBJECTIVE: To study the histologic regression and progression rates of cervical intraepithelial neoplasia (CIN) II and III after delivery and the effect the route of delivery has on the regression rates of CIN.
METHODS: Pregnant patients with satisfactory colposcopic examinations and biopsy-proven CIN II and III were identified. Delivery information and postpartum biopsy results were obtained by chart review.
RESULTS: Two hundred seventy-nine patients had antepartum biopsies of CIN II or CIN III. Of these, 126 women were excluded for the following reasons: lost to follow-up (75), human immunodeficiency virus positive (two), cesarean hysterectomy (four), and inadequate postpartum follow-up (45). This yielded a study group of 153 patients consisting of 82 with CIN II and 71 with CIN III. The regression rates were 68% and 70% among CIN II and CIN III patients (P = .78), respectively. Seven percent of patients with CIN II progressed to CIN III on postpartum evaluation. Twenty-five percent of those patients with CIN II and 30% of those with CIN III remained the same postpartum. No CIN lesions progressed to invasive carcinoma. There were no differences in regression rates or progression rates among the women who had vaginal deliveries (130), women who labored and then underwent cesarean (17), or women who proceeded to a cesarean without laboring (six).
CONCLUSION: We found similar high postpartum regression rates despite the route of delivery. We recommend conservative antepartum management with postpartum colposcopic evaluation regardless of route of delivery because we are unable to predict which of these lesions are more likely to regress.

PMID 10074979  Obstet Gynecol. 1999 Mar;93(3):359-62.
著者: J Peto, C Gilham, J Deacon, C Taylor, C Evans, W Binns, M Haywood, N Elanko, D Coleman, R Yule, M Desai
雑誌名: Br J Cancer. 2004 Aug 31;91(5):942-53. doi: 10.1038/sj.bjc.6602049.
Abstract/Text Cytology and histology records and cervical samples for HPV assay were obtained from a prospective cohort of 49 655 women attending clinics for routine cervical cytology in or near Manchester between 1988 and 1993. The women were followed up for cytological abnormality and neoplasia through the cytology laboratory's records. HPV at entry was assayed in an age- and period-stratified random sample of 7278 women and in prevalent and incident CIN3 cases. The prevalence of newly diagnosed CIN3 increased with time since last normal smear, indicating that most cases persist for several years. CIN3 prevalence did not increase further for screening intervals exceeding 5 years, however, suggesting that CIN3 eventually regresses cytologically. CIN2 prevalence increased less steeply with screening interval, while the prevalence of lesser abnormality was almost independent of screening interval. The prevalence of oncogenic HPV at entry declined from 19% among women aged under 25 to less than 3% at age 40 or above. Oncogenic HPV infection was strongly predictive of subsequent CIN3 (OR 17.2, 95% CI 10.4-28.4), but only weakly related to CIN2 (OR 2.3, 95% CI 0.5-10.7) and lesser abnormality (OR 1.4, 95% CI 0.8-2.5). At current incidence rates, the lifetime risk of developing CIN3 will be 9% in this population. The cumulative risk of CIN3 diagnosis among cytologically normal women with oncogenic HPV detected at entry was 28% (CI 18-43%) after 14 years. Persistence of oncogenic HPV may be more sensitive and specific than cytology for early detection of CIN3 and invasive cancer.

PMID 15292939  Br J Cancer. 2004 Aug 31;91(5):942-53. doi: 10.1038/sj.・・・
著者: W R Robinson, S Webb, J Tirpack, S Degefu, A G O'Quinn
雑誌名: Gynecol Oncol. 1997 Jan;64(1):153-5. doi: 10.1006/gyno.1996.4546.
Abstract/Text OBJECTIVE: Management of severe cervical dysplasia/possible microinvasive carcinoma during pregnancy is frequently associated with significant morbidity. The purpose of this study is to determine the efficacy of LOOP excision performed during pregnancy, and also to record the nature and frequency of complications of the procedure.
METHODS: Twenty women underwent LOOP excision during pregnancy. The gestational age range was 8-34 weeks. Data concerning indications, complications, and histopathologic results were recorded.
RESULTS: Fourteen of 20 (70%) had dysplastic changes in the LOOP specimen. Eight of 14 (57%) had involved margins. Nine of 19 (47%) had residual dysplasia 3 months postpartum, including 3 patients whose initial LOOP specimens were negative for dysplasia. Significant morbidity included 3 preterm births, 2 patients who required blood transfusion following LOOP, and 1 unexplained intrauterine fetal demise documented 4 weeks post-LOOP. The gestational age range of those patients who had significant morbidity was 27-34 weeks.
CONCLUSIONS: LOOP excision of the cervix during pregnancy does not consistently produce diagnostic specimens and is associated with a significant rate of residual disease. Morbidity appears similar to that of cone biopsy during pregnancy and occurs primarily when the procedure is performed in the third trimester. Until refinements in technique occur, LOOP excision during pregnancy should be reserved for limited indications.

PMID 8995565  Gynecol Oncol. 1997 Jan;64(1):153-5. doi: 10.1006/gyno.・・・
著者: Thomas C Wright, L Stewart Massad, Charles J Dunton, Mark Spitzer, Edward J Wilkinson, Diane Solomon, 2006 American Society for Colposcopy and Cervical Pathology-sponsored Consensus Conference
雑誌名: Am J Obstet Gynecol. 2007 Oct;197(4):340-5. doi: 10.1016/j.ajog.2007.07.050.
Abstract/Text A group of 146 experts representing 29 organizations and professional societies met Sept. 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. The management of low-grade cervical intraepithelial neoplasia (CIN) grade 1 has been modified significantly. Previously, management depended on whether colposcopy was satisfactory and treatment using ablative or excisional was acceptable for all women with CIN 1. In the new guidelines, cytological follow-up is the only recommended management option for women with CIN 1 who have low-grade referral cervical cytology, regardless of whether the colposcopic examination is satisfactory. Treatment is particularly discouraged in adolescents. The basic management of women in the general population with CIN 2,3 underwent only minor modifications, but options for the conservative management of adolescents with CIN 2,3 have been expanded. Moreover, management recommendations for women with biopsy-confirmed adenocarcinoma in situ are now included.

PMID 17904956  Am J Obstet Gynecol. 2007 Oct;197(4):340-5. doi: 10.101・・・
著者: L Stewart Massad, Mark H Einstein, Warner K Huh, Hormuzd A Katki, Walter K Kinney, Mark Schiffman, Diane Solomon, Nicolas Wentzensen, Herschel W Lawson, 2012 ASCCP Consensus Guidelines Conference
雑誌名: Obstet Gynecol. 2013 Apr;121(4):829-46. doi: 10.1097/AOG.0b013e3182883a34.
Abstract/Text A group of 47 experts representing 23 professional societies, national and international health organizations, and federal agencies met in Bethesda, MD, September 14-15, 2012, to revise the 2006 American Society for Colposcopy and Cervical Pathology Consensus Guidelines. The group's goal was to provide revised evidence-based consensus guidelines for managing women with abnormal cervical cancer screening tests, cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS) following adoption of cervical cancer screening guidelines incorporating longer screening intervals and co-testing. In addition to literature review, data from almost 1.4 million women in the Kaiser Permanente Northern California Medical Care Plan provided evidence on risk after abnormal tests. Where data were available, guidelines prescribed similar management for women with similar risks for CIN 3, AIS, and cancer. Most prior guidelines were reaffirmed. Examples of updates include: Human papillomavirus-negative atypical squamous cells of undetermined significance results are followed with co-testing at 3 years before return to routine screening and are not sufficient for exiting women from screening at age 65 years; women aged 21-24 years need less invasive management, especially for minor abnormalities; postcolposcopy management strategies incorporate co-testing; endocervical sampling reported as CIN 1 should be managed as CIN 1; unsatisfactory cytology should be repeated in most circumstances, even when HPV results from co-testing are known, while most cases of negative cytology with absent or insufficient endocervical cells or transformation zone component can be managed without intensive follow-up.

PMID 23635684  Obstet Gynecol. 2013 Apr;121(4):829-46. doi: 10.1097/AO・・・
著者: Jennifer S Smith, Lisa Lindsay, Brooke Hoots, Jessica Keys, Silvia Franceschi, Rachel Winer, Gary M Clifford
雑誌名: Int J Cancer. 2007 Aug 1;121(3):621-32. doi: 10.1002/ijc.22527.
Abstract/Text Data on human papillomavirus (HPV) type distribution in invasive and pre-invasive cervical cancer is essential to predict the future impact of HPV16/18 vaccines and HPV-based screening tests. A meta-analyses of HPV type distribution in invasive cervical cancer (ICC) and high-grade squamous intraepithelial lesions (HSIL) identified a total of 14,595 and 7,094 cases, respectively. In ICC, HPV16 was the most common, and HPV18 the second most common, type in all continents. Combined HPV16/18 prevalence among ICC cases was slightly higher in Europe, North America and Australia (74-77%) than in Africa, Asia and South/Central America (65-70%). The next most common HPV types were the same in each continent, namely HPV31, 33, 35, 45, 52 and 58, although their relative importance differed somewhat by region. HPV18 was significantly more prevalent in adeno/adenosquamous carcinoma than in squamous cell carcinoma, with the reverse being true for HPV16, 31, 33, 52 and 58. Among HSIL cases, HPV16/18 prevalence was 52%. However, HPV 16, 18 and 45 were significantly under-represented, and other high-risk HPV types significantly over-represented in HSIL compared to ICC, suggesting differences in type-specific risks for progression. Data on HPV-typed ICC and HSIL cases were particularly scarce from large regions of Africa and Central Asia.

Copyright (c) 2007 Wiley-Liss, Inc.
PMID 17405118  Int J Cancer. 2007 Aug 1;121(3):621-32. doi: 10.1002/ij・・・
著者: Cosette M Wheeler, William C Hunt, Mark Schiffman, Philip E Castle, Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study Group
雑誌名: J Infect Dis. 2006 Nov 1;194(9):1291-9. doi: 10.1086/507909. Epub 2006 Sep 27.
Abstract/Text BACKGROUND: Prospective data on the risks of cervical precancer associated with specific human papillomavirus (HPV) genotypes are limited.
METHODS: In 5060 women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS), we determined the cumulative 2-year risks of cervical intraepithelial neoplasia (CIN) grade 2 or more severe (> or =CIN2) and of grade 3 or more severe (> or =CIN3) for 38 individual HPV genotypes, as detected by polymerase chain reaction.
RESULTS: The most common HPV genotypes detected at baseline, in descending order of prevalence, were 16, 52, 51, 31, 18, 53, 39, 56, 62, 59, and 58. When detected as a single-type HPV infection, HPV-16 had a 2-year cumulative risk of 50.6% (95% confidence interval [CI], 44.1%-57.2%) for > or =CIN2 and 39.1% (95% CI, 32.9%-45.7%) for > or =CIN3. For other singly detected carcinogenic HPV types, the risk of > or =CIN2 ranged from 4.7% (for HPV-59) to 29.5% (for HPV-31), and the risk of > or =CIN3 ranged from 0.0% (for HPV-59) to 14.8% (for HPV-31). Multiple infections with HPV genotypes of different risk classes resulted in a risk that was similar to, and not significantly different from, the risk observed for the HPV genotype of the highest risk class.
CONCLUSIONS: Genotype-specific HPV testing may be useful for identifying women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions who are at higher and lower risk of prevalent and incipient cervical precancer.

PMID 17041856  J Infect Dis. 2006 Nov 1;194(9):1291-9. doi: 10.1086/50・・・
著者: R D Alvarez, C W Helm, R P Edwards, R W Naumann, E E Partridge, H M Shingleton, J A McGee, J B Hall, R V Higgins, J M Malone
雑誌名: Gynecol Oncol. 1994 Feb;52(2):175-9. doi: 10.1006/gyno.1994.1027.
Abstract/Text Three hundred seventy-five patients with CIN on referral Pap and with a distinct cervical lesion on colposcopy were prospectively randomized to treatment with LLETZ or to standard colposcopic evaluation with directed cervical biopsies, endocervical curettage, and laser ablation of the transformation zone for biopsy proven CIN. Of the 195 patients that randomized to treatment with LLETZ, 32.5% had no evidence of dysplasia, 26.5% had CIN 1, 17.3% had CIN 2, 22.7% had CIN 3, and 0.5% had microinvasive carcinoma on final histologic evaluation. Of the 180 patients randomized to laser ablation, initial cervical biopsies demonstrated no evidence of dysplasia in 52.8% of patients, CIN 1 in 22.0%, CIN 2 in 18.3%, and CIN 3 in 5.7%. Only 114 (63.3%) of the women in the laser group required therapy. Complications were comparable for each treatment arm. Only 6.7% of patients randomized to LLETZ and 4.4% with laser ablation had persistent CIN on follow-up Pap. LLETZ appears to be effective, well tolerated, and less expensive, but the cost savings advantage of LLETZ over laser ablation may not apply to patients with CIN 1 on referral Pap smear since many do not require treatment.

PMID 8314135  Gynecol Oncol. 1994 Feb;52(2):175-9. doi: 10.1006/gyno.・・・
著者: H B Krebs, L Pastore, B F Helmkamp
雑誌名: Am J Obstet Gynecol. 1993 Aug;169(2 Pt 1):289-93; discussion 293-5.
Abstract/Text OBJECTIVE: The study was undertaken to evaluate the use of the loop electrosurgical excision procedure as an outpatient hospital or surgicenter procedure.
STUDY DESIGN: The records of 358 patients treated for cervical intraepithelial neoplasia at a large community hospital over a 1-year period were reviewed.
RESULTS: The specimens obtained by loop electrosurgical excision procedure and laser cone excision were comparable in size but smaller than those by means of cold-knife conization. Seventy-two percent of loop electrosurgical excision procedure specimens consisted of two to eight tissue fragments (mean 3.4). In addition, 48% of the loop electrosurgical excision procedure specimens and 38% of laser cones had moderate or severe thermal artifacts. Fragmentation and cautery damage precluded orientation of tissue and evaluation of margins in 19% of the cases.
CONCLUSIONS: The advent of the loop electrosurgical excision procedure has shifted the management of cervical intraepithelial neoplasia from the office to the outpatient surgery centers. This negates and, in fact, reverses the advantage of loop electrosurgical excision procedure over other methods in regard to cost and convenience through evaluating and treating a patient with cervical intraepithelial neoplasia in one office visit. Loop electrosurgical excision procedures provide specimens that are inferior compared with cold-knife cones; therefore the role of loop electrosurgical excision procedure for the management of cervical intraepithelial neoplasia outside the office appears limited.

PMID 8362938  Am J Obstet Gynecol. 1993 Aug;169(2 Pt 1):289-93; discu・・・
著者: Lynn Sadler, Audrey Saftlas, Wenquan Wang, Melissa Exeter, John Whittaker, Lesley McCowan
雑誌名: JAMA. 2004 May 5;291(17):2100-6. doi: 10.1001/jama.291.17.2100.
Abstract/Text CONTEXT: It is unclear whether treatments for cervical intraepithelial neoplasia (CIN) increase the subsequent risk of preterm delivery. Most studies have lacked sufficient sample size, mixed heterogeneous subtypes of preterm delivery, and failed to control for confounding factors.
OBJECTIVE: To determine whether cervical laser and loop electrosurgical excision procedure (LEEP) treatments increase risk of preterm delivery and its subtypes.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study conducted among women evaluated at a colposcopy clinic serving Auckland, New Zealand (1988-2000), comparing delivery outcomes of untreated women (n = 426) and those treated (n = 652) with laser conization, laser ablation, or LEEP. Record linkage using unique health identifiers identified women who had subsequent deliveries.
MAIN OUTCOME MEASURES: Total preterm delivery and its subtypes, spontaneous labor and premature rupture of membranes before 37 weeks' gestation (pPROM).
RESULTS: The overall rate of preterm delivery was 13.8%. The rate of pPROM was 6.2% and the rate of spontaneous preterm delivery was 3.8%. Analyses showed no significant increase in risk of total preterm delivery (adjusted relative risk [aRR], 1.1; 95% confidence interval [CI], 0.8-1.5) or spontaneous preterm delivery (aRR, 1.3; 95% CI, 0.7-2.6) for any treatment. Risk of pPROM was significantly increased following treatment with laser conization (aRR, 2.7; 95% CI, 1.3-5.6) or LEEP (aRR, 1.9; 95% CI, 1.0-3.8), but not laser ablation (aRR, 1.1; 95% CI, 0.5-2.4). Moreover, risk of pPROM and total preterm delivery increased significantly with increasing height of tissue removed from the cervix in conization. Women in the highest tertile of cone height (> or =1.7 cm) had a greater than 3-fold increase in risk of pPROM compared with untreated women (aRR, 3.6; 95% CI, 1.8-7.5).
CONCLUSIONS: LEEP and laser cone treatments were associated with significantly increased risk of pPROM. Careful consideration should be given to treatment of CIN in women of reproductive age, especially when treatment might reasonably be delayed or targeted to high-risk cases.

PMID 15126438  JAMA. 2004 May 5;291(17):2100-6. doi: 10.1001/jama.291.・・・
著者: G Leiman, N A Harrison, A Rubin
雑誌名: Am J Obstet Gynecol. 1980 Jan 1;136(1):14-8.
Abstract/Text A retrospective study of 88 pregnancies occurring in 77 patients after cervical conization was undertaken to compare pregnancy outcome with cone size. Cone specimens were divided into two groups. Those measuring less than 2 cm in height or less than 4 cc in volume were considered to be "small cones" and those greater than 2 cm in height or 4 cc in volume were regarded as "large cones." The over-all normal term vaginal delivery rate was 46.6%, and was found to be inversely proportional to the size of the cone. The incidence of both spontaneous midtrimester abortion and prematurity increased in direct proportion to cone size. Cervical stenosis necessitating cesarean section was, however, noted to be a complication associated with small rather than large cones. It was concluded from this study that all postcone pregnancies should be regarded as high risk, preterm complications being particularly related to large cones.

PMID 7352477  Am J Obstet Gynecol. 1980 Jan 1;136(1):14-8.
著者: Ganesh Acharya, Ingvild Kjeldberg, Sidsel Mordt Hansen, Nils Sørheim, Bjarne Koster Jacobsen, Jan Martin Maltau
雑誌名: Arch Gynecol Obstet. 2005 Jul;272(2):109-12. doi: 10.1007/s00404-005-0727-1. Epub 2005 May 24.
Abstract/Text OBJECTIVE: Previous studies have shown conflicting results on the outcome of pregnancy following loop electrosurgical excision procedure (LEEP). The purpose of this study was to evaluate whether LEEP affects the outcome of pregnancy after 20 weeks' gestation.
METHODS: This is a matched cohort study of all women who had a LEEP for a biopsy-confirmed cervical intraepithelial neoplasia (CIN) in between December 1995 and December 2000 and subsequently delivered (after 20 weeks' gestation) at the University Hospital of Northern Norway. Women who had an ectopic pregnancy or an abortion (spontaneous or induced) following LEEP were excluded from analysis. Two controls matched for the date of delivery, age, parity, previous obstetric history and smoking habit were identified for each case using routinely entered data from the birth register. The main outcome measures were the duration of pregnancy and birth weight. Other variables recorded included the grade of cervical dysplasia, size of the electrosurgical loop, age, parity, pregnancy complications, mode of delivery, and perinatal outcome.
RESULTS: Of a total of 428 women of reproductive age who had LEEP performed during the study period, 89 had a pregnancy after the procedure. Ten women were excluded (three ectopic pregnancies, two induced abortions and five spontaneous abortions) from the study. Data from 79 women whose pregnancies progressed beyond 20 weeks and 158 matched controls were analysed. The mean age at the time of LEEP was 27 (range 19-36) years. The histological diagnosis was normal in 3 (3.8%), CIN1 in 5 (6.3%), CIN2 in 18 (22.8%), and CIN3 in 53 (67.1%) of the cases. Overall, mean gestation at delivery (38.3 vs. 39.1 weeks), mean birth weight (3,412 vs. 3,563 g), prevalence of preterm birth (11.4% vs. 10.8%) and low birth weight (10.1 vs. 5.1%) were not significantly different among the cases and controls. But when a relatively large loop (25 mm) had been used, the risk of preterm delivery (odds ratio 4.0) and low birth weight (odds ratio 14.0) was significantly higher than in controls. Pregnancy complications occurred more frequently (20 vs. 7%; p=0.006) among the cases than the controls.
CONCLUSION: LEEP in women with CIN did not significantly increase the risk of low birth weight or preterm birth in subsequent pregnancy in comparison to their controls, except when the size of electrosurgical loop was relatively large. However, the prevalence of pregnancy complications was significantly higher after LEEP.

PMID 15912414  Arch Gynecol Obstet. 2005 Jul;272(2):109-12. doi: 10.10・・・
著者: J Nuovo, J Melnikow, A R Willan, B K Chan
雑誌名: Int J Gynaecol Obstet. 2000 Jan;68(1):25-33.
Abstract/Text OBJECTIVE: To assess the effectiveness of cone biopsy, cryotherapy, laser ablation and the loop electrosurgical procedure in the treatment of squamous intraepithelial lesions.
METHOD: Systematic review of randomized controlled trials in subjects who underwent treatment of low- and high-grade squamous intraepithelial lesions with these modalities. Main outcome measures included the following: percent resolution and persistence of a lesion and notable complications for each procedure.
RESULT: Pooled rates of resolution for low-grade, high-grade, or combined squamous intraepithelial lesions were similar across the different treatment modalities (range 85.2-94.7%), with substantial overlap among the 95% confidence intervals. Significant hemorrhage occurred most frequently in subjects who received cone biopsy (4.6%) (95% CI: 2.15, 6.99), followed by laser ablation (1.75%) (95% CI: 0.70, 2.81), and LEEP (1.35%) (95% CI: 0.24, 2.47). No hemorrhages were reported among subjects who received cryotherapy. Study sample sizes were relatively small. There were no reported cases of progression to invasive cancer, but duration of follow-up (median follow-up time for all eligible studies = 12 months) was not sufficient to evaluate long-term outcomes.
CONCLUSIONS: There were no substantive differences in outcomes regarding persistence and resolution in the treatment of squamous intraepithelial lesions for subjects receiving cone biopsy, cryotherapy, laser ablation, or LEEP.

PMID 10687833  Int J Gynaecol Obstet. 2000 Jan;68(1):25-33.
著者: Joy Melnikow, Colleen McGahan, George F Sawaya, Thomas Ehlen, Andrew Coldman
雑誌名: J Natl Cancer Inst. 2009 May 20;101(10):721-8. doi: 10.1093/jnci/djp089. Epub 2009 May 12.
Abstract/Text BACKGROUND: Information on the long-term risk of cervical intraepithelial neoplasia (CIN) recurrence among women treated for CIN is limited yet critical for evidence-based surveillance recommendations.
METHODS: We retrospectively identified 37,142 women treated for CIN 1, 2, or 3 from January 1, 1986, through December 31, 2000 (CIN cohort), from the British Columbia Cancer Agency cytology database and linked their records with cancer registry and vital statistics data. Treatment included cryotherapy, loop electrosurgical excision procedure, cone biopsy, and laser vaporization or excision. A comparison cohort contained 71,213 women with normal cytology and no previous CIN diagnosis. Follow-up continued through December 31, 2004. Among women in both cohorts under active surveillance, we compared rates of CIN 2 or 3 (CIN 2/3) and cervical cancer. Cumulative incidence rates of CIN 2/3 and 95% confidence intervals (CIs) were estimated by a life table approach by using annual rates. Cumulative rates of invasive cancer were examined by the person-years method.
RESULTS: Overall observed cumulative rates of CIN 2/3 in the first 6 years after treatment were 14.0% (95% CI = 13.84% to 14.15%) for women originally treated for CIN 3, 9.3% (95% CI = 9.09% to 9.42%) for CIN 2, and 5.6% (95% CI = 4.91% to 5.21%) for CIN 1. Annual rates of CIN 2/3 were less than 1% after 6 years. Initial diagnosis, age, and treatment type were associated with a diagnosis of CIN 2/3 after treatment, with 6-year adjusted rates for women aged 40-49 years ranging from 2.6% (95% CI = 1.9% to 3.4%) for treatment of CIN 1 with the loop electrosurgical excision procedure to 34.0% (95% CI = 30.9% to 37.1%) for treatment of CIN 3 with cryotherapy. Overall incidence of invasive cancer (per 100,000 woman-years) was higher in the CIN cohort (37 invasive cancers, 95% CI = 30.6 to 42.5 cancers) than in the comparison cohort (six cancers, 95% CI = 4.3 to 7.7 cancers). Cryotherapy, compared with other treatments, was associated with the highest rate of subsequent disease (adjusted odds ratio for invasive cancer = 2.98, 95% CI = 2.09 to 4.60).
CONCLUSION: Risk of CIN 2/3 after treatment was associated with initial CIN grade, treatment type, and age. Long-term risk of invasive cancer remained higher among women treated for CIN, particularly those treated with cryotherapy.

PMID 19436026  J Natl Cancer Inst. 2009 May 20;101(10):721-8. doi: 10.・・・
著者: Y Nagai, T Maehama, T Asato, K Kanazawa
雑誌名: Gynecol Oncol. 2000 Nov;79(2):294-9. doi: 10.1006/gyno.2000.5952.
Abstract/Text OBJECTIVE: The aims of this study were (1) to examine whether HPV DNA is persistently detected in the cervix after therapeutic conization for CIN 3 and (2) to explore whether a patient with persistence of HPV infection is at risk of developing recurrent disease.
METHODS: Of 74 patients referred with CIN 3, 58 who were tested for HPV DNA in the pretreatment cervical lesions were enrolled in the study. After standard therapeutic conization, patients were followed prospectively at the outpatient clinic. Our follow-up protocol was to follow patients without therapeutic intervention as long as they developed no recurrence or recurrence of CIN 1 or 2, while patients who experienced recurrence of CIN 3 were recommended for reconization or hysterectomy. The polymerase chain reaction for detecting HPV DNA was performed using fresh cell samples from the cervix.
RESULTS: In 56 of 58 patients (96.6%), HPV DNAs were detected in their primary cervical lesions prior to conization. With regard to the distribution of HPV types, HPV type 16 family (types 16, 31, and 35) was identified in 28 cases (50.0%), type 18 family (types 18, 33 and 58) in 15 (26.8%), and type X in 18 (32.1%). Up to August 1999, all of the 58 patients have been followed with a mean follow-up period of 31.8 months (range: 12 to 73 months). After treatment, HPV DNA was persistently detected in 11 (19.6%) but negative in 45 (80.4%) of 56 HPV DNA-positive patients. HPV DNA was not detected in both HPV DNA-negative patients. Five of 11 persistently HPV DNA-positive patients (45.5%) developed CIN recurrence, while none of 45 persistently HPV DNA-negative patients did. Thus, there was a significant difference between the recurrence rates of these two groups (P < 0.0001). Both patients who were initially HPV DNA-negative developed no recurrence. Accordingly, the overall recurrence following conservative treatment for CIN 3 was 5 of 58 patients (8.6%).
CONCLUSIONS: Patients with persistent HPV infection after conization for CIN 3 should be especially closely followed because they are at increased risk of developing disease recurrence.

Copyright 2000 Academic Press.
PMID 11063660  Gynecol Oncol. 2000 Nov;79(2):294-9. doi: 10.1006/gyno.・・・
著者: Marc Arbyn, Peter Sasieni, Chris J L M Meijer, Christine Clavel, George Koliopoulos, Joakim Dillner
雑誌名: Vaccine. 2006 Aug 31;24 Suppl 3:S3/78-89. doi: 10.1016/j.vaccine.2006.05.117.
Abstract/Text BACKGROUND: More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods.
MATERIAL AND METHODS: A summary is given from recently published meta-analyses on three possible clinical applications of human papillomavirus (HPV)-DNA testing: triage of women with equivocal or low-grade cytological abnormalities; prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least, primary screening for cervical cancer and pre-cancer.
RESULTS: Consistent evidence is available indicating that HPV-triage with the Hybrid Capture-2 assay (HC2) is more accurate (significantly higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results. When triaging women with low-grade squamous intraepithelial lesions (LSIL), a reflex HC2 test does not show a significantly higher sensitivity, but a significantly lower specificity compared to a repeat Pap smear. After treatment of cervical lesions, HPV testing easily detects (with higher sensitivity and not lower specificity) residual or recurrent CIN than follow-up cytology. Primary screening with HC2 generally detects 23% (95% confidence interval, CI: 13-23%) more CIN-2, CIN-3, or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASCUS) or LSIL, but is 6% (95% CI: 4-8%) less specific. By combined HPV and cytology screening, a further 4% (95% CI: 3-5%) more CIN-3 lesions can be identified but at the expense of a 7% (95% CI: 5-9%) loss in specificity, in comparison with isolated HC2 screening.
CONCLUSIONS: Sufficient evidence exists to recommend HPV testing in triage of women with atypical cytology and in surveillance after treatment of CIN lesions. In the United States, recently reviewed knowledge has resulted in the approval of combined cytology and HC2 primary screening in women older than 30 years. However, in Europe, cytology-based screening still remains the standard screening method. The European screening policy will be reviewed based on the longitudinal results of randomised population trials which are currently underway.

PMID 16950021  Vaccine. 2006 Aug 31;24 Suppl 3:S3/78-89. doi: 10.1016/・・・

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