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頸部細胞診異常

著者: 若狭朋子 近畿大学奈良病院 病理診断科

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:2021/03/03
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: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. 検診受診率が低く、近年20歳代、30歳代の子宮頸がん患者が増加しているわが国においては妊娠初期の子宮頸がん検診の意義は大きい(推奨度1)。
  1. 頸部細胞診異常例に対してはハイリスクHPV(human papillomavirus)検査を含めた管理ガイドラインが策定されている(推奨度1)。
  1. 頸部病変を見逃さないためには病巣部の的確な細胞診、組織診が不可欠である(推奨度1)。
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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:
若狭朋子 : 未申告[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]

改訂のポイント:
  1. 定期レビューを行い、加筆修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 近年の初交年齢の低下や性行為の多様化により、子宮頸部病変の若年化傾向が顕著となってきた[1][2][3]
  1. 集団検診や定期検診の普及に伴って進行頸癌が減少した反面、前癌病変や初期癌が増加し、その管理や子宮を温存する保存的治療の重要性が高まりつつある[4][5]
  1. 頸部病変を見逃さないためには検診が最も重要で、病巣部の的確な細胞診、組織診が不可欠である。
  1. 子宮頸部細胞診判定方法として、ベセスダシステム2001準拠子宮頸部細胞診報告様式改定細胞診分類、通称「医会分類」)が提示され、全国的にベセスダシステムが定着しつつある[6]
  1. ベセスダシステム2001細胞診結果とその取扱い:扁平上皮系:<図表>
  1. ベセスダシステム2001細胞診結果とその取扱い:腺系:<図表>
  1. ベセスダシステムでは、標本の適正・不適正の評価に加えて、atypical squamous cell (ASC)、atypical glandular cell (AGC)など診断困難な異型細胞に対するカテゴリーが設けられている[6][7]
  1. ベセスダシステムに基づく頸部細胞診異常例に対して、ハイリスクhuman papillomavirus (HPV)検査を含めた管理ガイドラインが策定されている[8]
  1. ASCCP(米国コルポスコピー子宮頸部病理学会)のガイドライン:<図表>
  1. HPVタイピング検査を行う場合の管理指針:<図表>
問診・診察のポイント  
  1. 検診項目は、子宮頸部細胞診のほか、問診、視診、および内診が必要である。

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文献 

著者: Thomas C Wright, J Thomas Cox, L Stewart Massad, Leo B Twiggs, Edward J Wilkinson, ASCCP-Sponsored Consensus Conference
雑誌名: JAMA. 2002 Apr 24;287(16):2120-9.
Abstract/Text OBJECTIVE: To provide evidence-based consensus guidelines for the management of women with cervical cytological abnormalities and cervical cancer precursors.
PARTICIPANTS: A panel of 121 experts in the diagnosis and management of cervical cancer precursors, including representatives from 29 professional organizations, federal agencies, and national and international health organizations, were invited to participate in a consensus conference sponsored by the American Society for Colposcopy and Cervical Pathology (ASCCP).
EVIDENCE AND CONSENSUS PROCESS: Guidelines for the management of women with cervical cytological abnormalities were developed through a multistep process. Starting 6 months before the conference, working groups developed draft management guidelines based on formal literature reviews of English-language articles published in 1988-2001, as well as input from the professional community at large, obtained using interactive Internet-based bulletin boards. On September 6-8, 2001, the ASCCP Consensus Conference was held in Bethesda, Md. Guidelines with supporting evidence were presented and underwent discussion, revision, and voting.
CONCLUSIONS: Management of women with atypical squamous cells (ASC) depends on whether the Papanicolaou test is subcategorized as of undetermined significance (ASC-US) or as cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H). Women with ASC-US should be managed using a program of 2 repeat cytology tests, immediate colposcopy, or DNA testing for high-risk types of human papillomavirus (HPV). Testing for HPV DNA is the preferred approach when liquid-based cytology is used for screening. In most instances, women with ASC-H, low-grade squamous intraepithelial lesion, HSIL, and atypical glandular cells should be referred for immediate colposcopic evaluation.

PMID 11966387  JAMA. 2002 Apr 24;287(16):2120-9.
著者: Committee on Practice Bulletins—Gynecology
雑誌名: Obstet Gynecol. 2012 Nov;120(5):1222-38. doi: http://10.1097/AOG.0b013e318277c92a.
Abstract/Text The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because of widespread screening with cervical cytology. In 1975, the rate was 14.8 per 100,000 women. By 2008, it had been reduced to 6.6 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.38 per 100,000 women in 2008 (1). The American Cancer Society (ACS) estimates that there will be 12,170 new cases of cervical cancer in the United States in 2012, with 4,220 deaths from the disease (2). Cervical cancer is much more common worldwide, particularly in countries without screening programs, with an estimated 530,000 new cases of the disease and 275,000 resultant deaths each year (3, 4). When cervical cancer screening programs have been introduced into communities, marked reductions in cervical cancer incidence have followed (5, 6). New technologies for cervical cancer screening continue to evolve as do recommendations for managing the results. In addition, there are different risk-benefit considerations for women at different ages, as reflected in age-specific screening recommendations. The ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) have recently updated their joint guidelines for cervical cancer screening (7), and an update to the U.S. Preventive Services Task Force recommendations also has been issued (8). The purpose of this document is to provide a review of the best available evidence regarding screening for cervical cancer.

PMID 23090560  Obstet Gynecol. 2012 Nov;120(5):1222-38. doi: http://10・・・
著者: P Sasieni, J Adams, J Cuzick
雑誌名: Br J Cancer. 2003 Jul 7;89(1):88-93. doi: 10.1038/sj.bjc.6600974.
Abstract/Text While most experts agree that cervical screening is effective, there remains controversy over the most appropriate screening interval. Annual screening is common in North America. In England, some argue for 3-yearly screening while others believe 5-yearly screening is adequate, and the frequency varies from one part of the country to another. Screening histories of 1305 women aged 20-69 years, diagnosed with frankly invasive cervical cancer and 2532 age-matched controls were obtained from UK screening programme databases. Data were analysed in terms of time since last negative, and time since last screening smear. Five-yearly screening offers considerable protection (83%) against cancer at ages 55-69 years and even annual screening offers only modest additional protection (87%). Three-yearly screening offers additional protection (84%) over 5-yearly screening (73%) for cancers at ages 40-54 years, but is almost as good as annual screening (88%). In women aged 20-39 years, even annual screening is not as effective (76%) as 3-yearly screening in older women, and 3 years after screening cancer rates return to those in unscreened women. This calls into question the policy of having a uniform screening interval from age 20 to 64 years and stresses the value of screening in middle-aged women. British Journal of Cancer (2003) 89, 88-93. doi:10.1038/sj.bjc.6600974 www.bjcancer.com

PMID 12838306  Br J Cancer. 2003 Jul 7;89(1):88-93. doi: 10.1038/sj.bj・・・
著者: George F Sawaya, K John McConnell, Shalini L Kulasingam, Herschel W Lawson, Karla Kerlikowske, Joy Melnikow, Nancy C Lee, Ginny Gildengorin, Evan R Myers, A Eugene Washington
雑誌名: N Engl J Med. 2003 Oct 16;349(16):1501-9. doi: 10.1056/NEJMoa035419.
Abstract/Text BACKGROUND: Although contemporary guidelines suggest that the intervals between Papanicolaou tests can be extended to three years among low-risk women with previous negative tests, the excess risk of cervical cancer associated with less frequent than annual screening is uncertain.
METHODS: We determined the prevalence of biopsy-proven cervical neoplasia among 938,576 women younger than 65 years of age, stratified according to the number of previous consecutive negative Papanicolaou tests. Using a Markov model that estimates the rate at which dysplasia will progress to cancer, we estimated the risk of cancer within three years after one or more negative Papanicolaou tests, as well as the number of additional Papanicolaou tests and colposcopic examinations that would be required to avert one case of cancer given a particular interval between screenings.
RESULTS: Among 31,728 women 30 to 64 years of age who had had three or more consecutive negative tests, the prevalence of biopsy-proven cervical intraepithelial neoplasia of grade 2 was 0.028 percent and the prevalence of grade 3 neoplasia was 0.019 percent; none of the women had invasive cervical cancer. According to our model, the estimated risk of cancer with annual Papanicolaou tests for three years was 2 in 100,000 among women 30 to 44 years of age, 1 in 100,000 among women 45 to 59 years of age, and 1 in 100,000 among women 60 to 64 years of age; these risks would be 5 in 100,000, 2 in 100,000, and 1 in 100,000, respectively, if screening were performed once three years after the last negative test. To avert one additional case of cancer by screening 100,000 women annually for three years rather than once three years after the last negative test, an average of 69,665 additional Papanicolaou tests and 3861 colposcopic examinations would be needed in women 30 to 44 years of age and an average of 209,324 additional Papanicolaou tests and 11,502 colposcopic examinations in women 45 to 59 years of age.
CONCLUSIONS: As compared with annual screening for three years, screening performed once three years after the last negative test in women 30 to 64 years of age who have had three or more consecutive negative Papanicolaou tests is associated with an average excess risk of cervical cancer of approximately 3 in 100,000.

Copyright 2003 Massachusetts Medical Society
PMID 14561792  N Engl J Med. 2003 Oct 16;349(16):1501-9. doi: 10.1056/・・・
著者: M E Sherman, D Solomon, M Schiffman, ASCUS LSIL Triage Study Group
雑誌名: Am J Clin Pathol. 2001 Sep;116(3):386-94. doi: 10.1309/JM3V-U4HP-W8HJ-68XV.
Abstract/Text Cytologic detection of high-grade squamous intraepithelial lesions (HSILs) is critical to cervical cancer prevention. Therefore, identifying "equivocal HSIL" (ASCUS [atypical squamous cells of undetermined significance]-H) may be useful. Accordingly, we compared findings associated with "equivocal low-grade SIL" (ASCUS-L), ASCUS-H, and HSIL using data from the ASCUS LSIL (low-grade squamous intraepithelial lesion) Triage Study. The frequency of oncogenic human papillomavirus (HPV) DNA detection and underlying lesions cervical intraepithelial neoplasia (CIN) 2 or worse or CIN 3 or worse in women with ASCUS-H was intermediate between that of ASCUS-L and HSIL. Oncogenic HPV DNA was associated with 85.6% of ASCUS-H ThinPreps and 69.8% of ASCUS-H smears. Histopathologic lesions CIN 2 or worse were associated with 40.5% of ASCUS-H ThinPreps and 27.2% of ASCUS-H smears (mostly CIN 3). Nevertheless, numerically more lesions CIN 2 or worse were preceded by ASCUS-L than by ASCUS-H because ASCUS-L was more common. ASCUS-H is an uncommon interpretation that derives clinical usefulness from its high positive predictive value for lesions CIN 2 or worse.

PMID 11554167  Am J Clin Pathol. 2001 Sep;116(3):386-94. doi: 10.1309/・・・
著者: ASCUS-LSIL Traige Study (ALTS) Group
雑誌名: Am J Obstet Gynecol. 2003 Jun;188(6):1383-92.
Abstract/Text OBJECTIVE: This study was undertaken to compare alternative strategies for the initial management of a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS).
STUDY DESIGN: A total of 3488 women with a community-based ASCUS interpretation were randomly assigned to immediate colposcopy, triage that was based on enrollment HPV DNA testing and liquid-based cytology at a colposcopy referral threshold of high-grade squamous intraepithelial lesion (HSIL), or conservative management based on repeat cytology at a referral threshold of HSIL. All arms included 2 years of semiannual follow-up and colposcopy at exit. Loop electrosurgical excision procedure was offered to women with histologic diagnoses of cervical intraepithelial neoplasia (CIN) grade 2 or 3 at any visit or persistent CIN grade 1 at exit. The study end point was 2-year cumulative diagnosis of CIN grade 3.
RESULTS: The 2-year cumulative diagnosis of CIN grade 3 was 8% to 9% in all study arms. The immediate colposcopy strategy yielded 53.6% sensitivity for cumulative cases of CIN grade 3 diagnosed over 2 years. The human papillomavirus (HPV) triage strategy referred 55.6% of women and detected 72.3% of cumulative cases of CIN grade 3. A conservative management strategy of repeat cytology at the HSIL threshold referred 12.3% of women while detecting 54.6% of cumulative CIN grade 3. To compare triage tests, we re-estimated the performance of HPV and cytology in successfully referring women with underlying CIN grade 3 (ie, ignoring the insensitivity we discovered in colposcopically directed biopsies). A single enrollment HPV test identified 92.4% of the women diagnosed with CIN grade 3. Serial cytology, even at an ASCUS threshold, would have required two visits to achieve similar sensitivity (95.4%) and would have referred 67.1% to colposcopy.
CONCLUSION: HPV triage is at least as sensitive as immediate colposcopy for detecting CIN grade 3 and refers about half as many women to colposcopy. Follow-up that used repeat cytology is sensitive at an ASCUS referral threshold but requires two follow-up visits and ultimately more colposcopic examinations than HPV triage.

PMID 12824967  Am J Obstet Gynecol. 2003 Jun;188(6):1383-92.
著者: Philip E Castle, Barbara Fetterman, Nancy Poitras, Thomas Lorey, Ruth Shaber, Walter Kinney
雑誌名: Obstet Gynecol. 2010 Feb;115(2 Pt 1):243-8. doi: 10.1097/AOG.0b013e3181c799a3.
Abstract/Text OBJECTIVE: To quantify the age-specific and reproductive organ-specific cancer risk after an atypical glandular cell (AGC) cytologic interpretation in large clinic-based sample in which routine high-risk human papillomavirus (HPV) testing is conducted.
METHODS: : To estimate the absolute risk of cervical precancer, cervical cancer, and endometrial cancer in women with AGC cytology, we conducted a cross-sectional study of women with AGC cytology (n=1,422) in a large health maintenance organization that introduced high-risk HPV DNA testing into cervical cancer screening in 2003. Risks and binomial exact 95% confidence intervals (CIs) of cervical intraepithelial neoplasia grade 2 or more severe (CIN 2 or worse) and endometrial cancer were calculated.
RESULTS: A total of 238 women with AGC cytology (16.7%, 95% CI 14.8-18.8%) were diagnosed with CIN 2 or worse, endometrial cancer, or other cancers. Among women aged 50 years or older, 420 high-risk HPV-negative women were at a 10.5% (95% CI 7.7-13.8%) risk of endometrial cancer, and 77 high-risk HPV-positive women were at a 10.4% (95% CI 4.6-19.4%) risk of cervical cancer and 0% (95% CI 0.0-4.7%) risk of endometrial cancer.
CONCLUSION: High-risk HPV testing may distinguish between risk of endometrial cancer and cervical cancer in women with AGC cervical cytology, particularly in women aged 50 years or older.
LEVEL OF EVIDENCE: III.

PMID 20093895  Obstet Gynecol. 2010 Feb;115(2 Pt 1):243-8. doi: 10.109・・・
著者: L Stewart Massad, Yvonne C Collins
雑誌名: J Reprod Med. 2003 Jan;48(1):1-6.
Abstract/Text OBJECTIVE: To enhance the yield of endocervical curettage (ECC) by defining risks for abnormality.
STUDY DESIGN: Demographic and medical information collected at colposcopy and subsequent histology were reviewed retrospectively. Statistical analysis was by t and chi 2 tests.
RESULTS: Among 2,287 women undergoing ECC at colposcopy, in only 105 (5%) did positive ECC require excisional therapy that would not otherwise have been recommended. Women with positive ECC were older (mean, 39.0 vs. 33.2 years; P < .001) and of higher parity (mean, 3.0 vs. 2.0 births; P < .001), with earlier first intercourse (at 16.6 vs. 17.2 years, P = .006), more unsatisfactory colposcopy (148 [27%] of 545 women with unsatisfactory colposcopy vs. 183 [12%] of 1,523 women with satisfactory colposcopy; P < .001) and more colposcopic impressions of cervical intraepithelial neoplasia (CIN) 2-3 (163 [51%] of 323 vs. 443 [25.6%] of 1,730 women with low grade or a negative impression; P < .001). The likelihood of missed CIN 2-3 was 0.4%, with no missed cancers among women with satisfactory colposcopy and either a normal colposcopic impression (1/254) or nulliparity (2/474).
CONCLUSION: ECC identifies otherwise-undetected preinvasive and invasive lesions but may be avoided in women with satisfactory colposcopy who are nulliparous or have no colposcopic lesions.

PMID 12611087  J Reprod Med. 2003 Jan;48(1):1-6.
著者: Robert G Pretorius, Wen-Hua Zhang, Jerome L Belinson, Man-Ni Huang, Ling-Ying Wu, Xun Zhang, You-Lin Qiao
雑誌名: Am J Obstet Gynecol. 2004 Aug;191(2):430-4. doi: 10.1016/j.ajog.2004.02.065.
Abstract/Text OBJECTIVES: The purpose of this study was to determine the relative importance of colposcopically directed biopsy, random biopsy, and endocervical curettage (ECC) in diagnosing > or =cervical intraepithelial neoplasia (CIN) II. Study design During a screening study, 364 women with satisfactory colposcopy and > or =CIN II were diagnosed. All colposcopically detected lesions were biopsied. If colposcopy showed no lesion in a cervical quadrant, a random biopsy was obtained at the squamocolumnar junction in that quadrant. ECC was then performed.
RESULTS: The diagnosis of > or =CIN II was made on a colposcopically directed biopsy in 57.1%, random biopsy in 37.4%, and ECC in 5.5% of women. The yield of > or =CIN II for random biopsy when cytology was high grade (17.6%) exceeded that when cytology was low grade (2.8%). One of 20 women diagnosed solely by ECC had invasive cancer.
CONCLUSION: Even when colposcopy is satisfactory, ECC should be performed. If cytology is high grade, random biopsies should be considered.

PMID 15343217  Am J Obstet Gynecol. 2004 Aug;191(2):430-4. doi: 10.101・・・
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: M Arbyn, M Kyrgiou, C Simoens, A O Raifu, G Koliopoulos, P Martin-Hirsch, W Prendiville, E Paraskevaidis
雑誌名: BMJ. 2008 Sep 18;337:a1284. Epub 2008 Sep 18.
Abstract/Text OBJECTIVE: To assess the relative risk of perinatal mortality, severe preterm delivery, and low birth weight associated with previous treatment for precursors of cervical cancer.
DATA SOURCES: Medline and Embase citation tracking from January 1960 to December 2007. Selection criteria Eligible studies had data on severe pregnancy outcomes for women with and without previous treatment for cervical intraepithelial neoplasia. Considered outcomes were perinatal mortality, severe preterm delivery (<32/34 weeks), extreme preterm delivery (<28/30 weeks), and low birth weight (<2000 g, <1500 g, and <1000 g). Excisional and ablative treatment procedures were distinguished.
RESULTS: One prospective cohort and 19 retrospective studies were retrieved. Cold knife conisation was associated with a significantly increased risk of perinatal mortality (relative risk 2.87, 95% confidence interval 1.42 to 5.81) and a significantly higher risk of severe preterm delivery (2.78, 1.72 to 4.51), extreme preterm delivery (5.33, 1.63 to 17.40), and low birth weight of <2000 g (2.86, 1.37 to 5.97). Laser conisation, described in only one study, was also followed by a significantly increased chance of low birth weight of <2000 g and <1500 g. Large loop excision of the transformation zone and ablative treatment with cryotherapy or laser were not associated with a significantly increased risk of serious adverse pregnancy outcomes. Ablation by radical diathermy was associated with a significantly higher frequency of perinatal mortality, severe and extreme preterm delivery, and low birth weight below 2000 g or 1500 g.
CONCLUSIONS: In the treatment of cervical intraepithelial neoplasia, cold knife conisation and probably both laser conisation and radical diathermy are associated with an increased risk of subsequent perinatal mortality and other serious pregnancy outcomes, unlike laser ablation and cryotherapy. Large loop excision of the transformation zone cannot be considered as completely free of adverse outcomes.

PMID 18801868  BMJ. 2008 Sep 18;337:a1284. Epub 2008 Sep 18.
著者: Maija Jakobsson, Mika Gissler, Jorma Paavonen, Anna-Maija Tapper
雑誌名: Obstet Gynecol. 2009 Sep;114(3):504-10. doi: 10.1097/AOG.0b013e3181b052de.
Abstract/Text OBJECTIVE: To study whether loop electrosurgical excision procedure (LEEP) conization is associated with preterm birth and to study the effect of cone size on preterm birth.
METHODS: This was a retrospective cohort study from Southern Finland conducted from 1997 to 2003, with a follow-up for subsequent births until 2006. We identified the cases from the Hospital Discharge Register and Medical Birth Register and collected additional information from the hospital records. Our cohort consisted of 624 women who delivered after LEEP conization. We calculated expected preterm birth rates by using the Medical Birth Register data. In subgroup analysis (n=258 women) we used internal controls, ie, deliveries before the treatment. The main outcome measure was preterm birth rate in different subgroups.
RESULTS: The risk for preterm delivery (before 37 weeks) was increased almost threefold (relative risk [RR] 2.61, 95% confidence interval [CI] 2.02-3.20; number needed to treat for harm=14) and repeat treatments more than fivefold (RR 5.15, 95% CI 2.45-7.84; number needed to treat for harm=5) after LEEP conization compared with the background rate of preterm birth (4.61%). Large or repeat cones increased the risk twofold (RR 2.45, 95% CI 1.38-3.53) when compared with small or medium-sized cones. For women having a birth before and after LEEP conization, the preterm birth rate was 6.5% before and 12.0% after the procedure (RR 1.94, 95% CI 1.10-3.40; number needed to treat for harm=18). Adjusting for maternal age, parity, or both did not change the results. The risk for preterm birth was especially increased (RR 3.38, 95% CI 2.31-4.94) among women without previous preterm birth.
CONCLUSION: Loop electrosurgical excision procedure surgery of the cervix predisposes patients to preterm birth. Loop electrosurgical excision procedure conization increased the risk for preterm birth especially among women without previous preterm birth. The rates were highest after repeat procedures.
LEVEL OF EVIDENCE: II.

PMID 19701027  Obstet Gynecol. 2009 Sep;114(3):504-10. doi: 10.1097/AO・・・
著者: Masatsugu Ueda, Ken Ueki, Masanori Kanemura, Shinji Izuma, Hiroyuki Yamaguchi, Koji Nishiyama, Yoshimichi Tanaka, Yoshito Terai, Minoru Ueki
雑誌名: Gynecol Oncol. 2006 Apr;101(1):143-6. doi: 10.1016/j.ygyno.2005.10.001. Epub 2005 Nov 2.
Abstract/Text OBJECTIVE: The clinical efficacy of conservative treatment using Nd-YAG laser technique for cervical intraepithelial neoplasia (CIN) was evaluated in a large series of CIN patients based on the long-term follow-up results.
METHODS: We have treated 2107 women preoperatively diagnosed as having CIN by Nd-YAG contact laser conization with vaporization of the base. Their postoperative histologic findings and clinical outcomes were evaluated.
RESULTS: The cone specimen was reported as showing that 1956 (92.8%) of 2107 cases had no CIN or CIN 1-3 and 151 (7.2%) cases had invasive diseases. 1956 cases without invasive diseases were followed up for 16 to 252 months. Incomplete excision occurred in 230 (12.3%) of 1874 patients with CIN lesion in the cone specimen, but failure rate (persistence or recurrence) was only 1.2%. 192 (83.5%) of 230 postoperative CIN patients with positive surgical margins showed no abnormal cytology or colposcopy during follow-up period. Preoperative underdiagnosis of biopsy results compared with cytologic or colposcopic findings elevated the risk for incomplete excision and failure rate.
CONCLUSION: The combination of laser excision and vaporization of the base was useful to detect unexpected invasive disease and revealed excellent therapeutic effects for CIN. Preoperative cytologic or colposcopic findings should be taken into account for the conservative treatment of CIN.

PMID 16271274  Gynecol Oncol. 2006 Apr;101(1):143-6. doi: 10.1016/j.yg・・・
著者: H Yamaguchi, M Ueda, M Kanemura, S Izuma, K Nishiyama, Y Tanaka, S Noda
雑誌名: Int J Gynecol Cancer. 2007 Mar-Apr;17(2):455-9. doi: 10.1111/j.1525-1438.2006.00868.x. Epub 2007 Feb 19.
Abstract/Text The objective of this study was to evaluate the clinical efficacy of conservative laser therapy for early-stage cervical cancer. Seven hundred fifty-two and 271 patients with carcinoma in situ (CIS) and microinvasive squamous cell carcinoma (MIC), respectively, were treated by laser conization with vaporization. One hundred eighty-four patients with preclinical invasive diseases underwent radical surgery without conization. Their postoperative histologic findings and clinical outcomes were evaluated retrospectively. The cone specimens of 1023 cases were reported as showing that 54 had dysplasia, 663 had CIS, 239 had stage Ia1 without lymph vascular space invasion (LVSI), 14 had stage Ia1 with LVSI, 14 had stage Ia2, and 39 had stage Ib1 diseases. Incomplete excision occurred in 4 (7.4%) of 54 dysplasia, 48 (7.2%) of 663 CIS, and 16 (6.7%) of 239 stage Ia1 cases, but failure rates were only 1 (1.9%), 8 (1.2%), and 4 (1.7%), respectively. The other 67 of 1023 cases underwent abdominal operation. Final pathology results were analyzed for 67 and 184 cases with stages Ia1 to Ib1 receiving radical surgery with or without initial laser therapy. Lymph node metastasis was not observed in 154 Ia1 and 30 Ia2 with stromal invasion of under 4 mm in depth regardless of LVSI, but was detected in 2 of 16 Ia2 with stromal invasion of over 4 mm in depth and in 9 of 51 Ib1 cases. CIS and Ia1 disease without LVSI can be treated only by laser therapy. The limit of stromal invasion for conservative laser therapy in stage Ia cancer may be 4 mm in depth regardless of LVSI.

PMID 17316359  Int J Gynecol Cancer. 2007 Mar-Apr;17(2):455-9. doi: 10・・・
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):346-55. doi: 10.1016/j.ajog.2007.07.047.
Abstract/Text A group of 146 experts representing 29 organizations and professional societies met September 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. Recommendations for managing atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion (LSIL) are essentially unchanged. Changes were made for managing these conditions in adolescents for whom cytological follow-up for 2 years was approved. Recommendations for managing high-grade squamous intraepithelial lesion (HSIL) and atypical glandular cells (AGC) also underwent only minor modifications. More emphasis is placed on immediate screen-and-treat approaches for HSIL. Human papillomavirus (HPV) testing is incorporated into the management of AGC after their initial evaluation with colposcopy and endometrial sampling. The 2004 Interim Guidance for HPV testing as an adjunct to cervical cytology for screening in women 30 years of age and older was formally adopted with only very minor modifications.

PMID 17904957  Am J Obstet Gynecol. 2007 Oct;197(4):346-55. doi: 10.10・・・
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: Debbie Saslow, Carolyn D Runowicz, Diane Solomon, Anna-Barbara Moscicki, Robert A Smith, Harmon J Eyre, Carmel Cohen, American Cancer Society
雑誌名: CA Cancer J Clin. 2002 Nov-Dec;52(6):342-62.
Abstract/Text An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical neoplasia and cancer, based on recommendations from a formal review and recent workshop, is presented. The new screening recommendations address when to begin screening, when screening may be discontinued, whether to screen women who have had a hysterectomy, appropriate screening intervals, and new screening technologies, including liquid-based cytology and HPV DNA testing.

PMID 12469763  CA Cancer J Clin. 2002 Nov-Dec;52(6):342-62.
著者: American College of Obstetricians and Gynecologists
雑誌名: Obstet Gynecol. 2005 Apr;105(4):905-18.
Abstract/Text More than 15 years ago, a relationship between human papillomavirus (HPV) infection and cervical cancer was recognized. Since then, important strides in understanding the virus have been made, particularly in the following areas: modes of transmission and risk factors associated with transmission; the oncogenic potential of specific viral types and the mechanism by which they cause cancer; and the spectrum of infection, ranging from asymptomatic carrier states to overt warts, preneoplastic lesions, and invasive cancer. Sophisticated new tests for the detection of HPV that hold great promise for improved screening for cervical cancer precursors and invasive cancer and for the triage of abnormal cervical cytology also have been developed. Understanding the immunology of HPV has allowed the development of new and more effective treatment modalities for HPV infection and the preliminary development of primary prevention modalities, including HPV vaccines.

PMID 15802436  Obstet Gynecol. 2005 Apr;105(4):905-18.
著者: ACOG Committee on Practice Bulletins
雑誌名: Obstet Gynecol. 2003 Aug;102(2):417-27.
Abstract/Text Although cervical cancer was the leading cause of cancer death in American women as recently as the 1930s, both the incidence and mortality from cervical cancer have decreased by almost one half since the early 1970s, largely as a result of widespread screening with the Pap test. However, the annual incidence rate has remained at approximately 8 cases per 100,000 women over the past few years. New technology for performing cervical cytology is evolving rapidly as are recommendations for classifying and interpreting the results. The purpose of this document is to provide a review of the best available evidence on screening for cervical cancer. Specific equipment and techniques for performing cervical cytology and interpretation of the results are discussed elsewhere.

PMID 12907124  Obstet Gynecol. 2003 Aug;102(2):417-27.
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: 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: 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: 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: 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: J Akahira, R Konno, T Moriya, H Yamakawa, T Igarashi, K Ito, S Sato, A Yajima
雑誌名: Gynecol Obstet Invest. 2000;50(4):264-8. doi: 10329.
Abstract/Text The Harmonic Scalpel((R)) (HS) is a new surgical tool that cuts and coagulates by converting electrical energy into ultrasonic mechanical vibrations. The purpose of our study was to compare HS conization and the loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) with respect to both clinical and pathological features. Fifty-one consecutive women conservatively treated (29 with LEEP and 22 with HS conization) for CIN III were retrospectively reviewed. The background of the patients was similar. Operative time, intra- and postoperative blood loss were not significantly different. With HS conization all specimens were removed in one piece, but with LEEP the median number of specimens obtained per patient was 3.3 (p<0.0001) with a maximum of 5. The depth of thermal artifacts at the endocervical margin was significantly less with HS conization (0.20 mm) than with LEEP (0.30 mm; p = 0.0006). This new method produced an ideal-shaped specimen without increasing complications and thermal artifacts compared with LEEP.

PMID 11093051  Gynecol Obstet Invest. 2000;50(4):264-8. doi: 10329.
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: 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: Marie-Hélène Mayrand, Eliane Duarte-Franco, Isabel Rodrigues, Stephen D Walter, James Hanley, Alex Ferenczy, Sam Ratnam, François Coutlée, Eduardo L Franco, Canadian Cervical Cancer Screening Trial Study Group
雑誌名: N Engl J Med. 2007 Oct 18;357(16):1579-88. doi: 10.1056/NEJMoa071430.
Abstract/Text BACKGROUND: To determine whether testing for DNA of oncogenic human papillomaviruses (HPV) is superior to the Papanicolaou (Pap) test for cervical-cancer screening, we conducted a randomized trial comparing the two methods.
METHODS: We compared HPV testing, using an assay approved by the Food and Drug Administration, with conventional Pap testing as a screening method to identify high-grade cervical intraepithelial neoplasia in women ages 30 to 69 years in Montreal and St. John's, Canada. Women with abnormal Pap test results or a positive HPV test (at least 1 pg of high-risk HPV DNA per milliliter) underwent colposcopy and biopsy, as did a random sample of women with negative tests. Sensitivity and specificity estimates were corrected for verification bias.
RESULTS: A total of 10,154 women were randomly assigned to testing. Both tests were performed on all women in a randomly assigned sequence at the same session. The sensitivity of HPV testing for cervical intraepithelial neoplasia of grade 2 or 3 was 94.6% (95% confidence interval [CI], 84.2 to 100), whereas the sensitivity of Pap testing was 55.4% (95% CI, 33.6 to 77.2; P=0.01). The specificity was 94.1% (95% CI, 93.4 to 94.8) for HPV testing and 96.8% (95% CI, 96.3 to 97.3; P<0.001) for Pap testing. Performance was unaffected by the sequence of the tests. The sensitivity of both tests used together was 100%, and the specificity was 92.5%. Triage procedures for Pap or HPV testing resulted in fewer referrals for colposcopy than did either test alone but were less sensitive. No adverse events were reported.
CONCLUSIONS: As compared with Pap testing, HPV testing has greater sensitivity for the detection of cervical intraepithelial neoplasia. (Current Controlled Trials number, ISRCTN57612064 [controlled-trials.com].).

Copyright 2007 Massachusetts Medical Society.
PMID 17942871  N Engl J Med. 2007 Oct 18;357(16):1579-88. doi: 10.1056・・・
著者: Thomas C Wright, Mark Schiffman, Diane Solomon, J Thomas Cox, Francisco Garcia, Sue Goldie, Kenneth Hatch, Kenneth L Noller, Nancy Roach, Carolyn Runowicz, Debbie Saslow
雑誌名: Obstet Gynecol. 2004 Feb;103(2):304-9. doi: 10.1097/01.AOG.0000109426.82624.f8.
Abstract/Text Human papillomavirus (HPV) DNA testing was recently approved by the Food and Drug Administration for use as an adjunct to cytology for cervical cancer screening. To help provide guidance to clinicians and patients when using HPV DNA testing as an adjunct to cervical cytology for screening, a workshop was cosponsored by the National Institutes of Health-National Cancer Institute, American Society of Colposcopy and Cervical Pathology (ASCCP), and American Cancer Society. Consensus was reached based on a literature review, expert opinion, and unpublished results from large ongoing screening studies. The conclusions of the workshop were that HPV DNA testing may be added to cervical cytology for screening in women aged 30 years or more. Women whose results are negative by both HPV DNA testing and cytology should not be rescreened before 3 years. Women whose results are negative by cytology, but are high-risk HPV DNA positive, are at a relatively low risk of having high-grade cervical neoplasia, and colposcopy should not be performed routinely in this setting. Instead, HPV DNA testing along with cervical cytology should be repeated in these women at 6 to 12 months. If test results of either are abnormal, colposcopy should then be performed. This guidance should assist clinicians in utilizing HPV DNA testing in an effective manner, while minimizing unnecessary evaluations and treatments.

PMID 14754700  Obstet Gynecol. 2004 Feb;103(2):304-9. doi: 10.1097/01.・・・
著者: Jack Cuzick, Christine Clavel, Karl-Ulrich Petry, Chris J L M Meijer, Heike Hoyer, Samuel Ratnam, Anne Szarewski, Philippe Birembaut, Shalini Kulasingam, Peter Sasieni, Thomas Iftner
雑誌名: Int J Cancer. 2006 Sep 1;119(5):1095-101. doi: 10.1002/ijc.21955.
Abstract/Text Several studies suggest that HPV testing is more sensitive than cytology in primary cervical screening. These studies had different designs and were reported in different ways. Individual patient data were collected for all European and North American studies in which cytology was routinely performed and HPV testing was included as an additional parallel test. More than 60,000 women were included. The sensitivity and specificity of HPV testing were compared with routine cytology, both overall and for ages <35, 35-49 and 50+. The age-specific prevalence of high risk HPV (hr-HPV) was also analysed. HPV testing was substantially more sensitive in detecting CIN2+ than cytology (96.1% vs. 53.0%) but less specific (90.7% vs. 96.3%). The sensitivity of HPV testing was similar in all studies carried out in different areas of Europe and North America, whereas the sensitivity of cytology was highly variable. HPV sensitivity was uniformly high at all ages, whereas the sensitivity of cytology was substantially better in women over the age of 50 than in younger women (79.3% vs. 59.6%). The specificity of both tests increased with age. Positivity rates for HPV testing in women without high-grade CIN were region dependent. These results support the use of HPV testing as the sole primary screening test, with cytology reserved for women who test HPV positive. Large demonstration projects are needed to fully evaluate this strategy.

Copyright 2006 Wiley-Liss, Inc.
PMID 16586444  Int J Cancer. 2006 Sep 1;119(5):1095-101. doi: 10.1002/・・・
著者: Susanne Kjaer, Estrid Høgdall, Kirsten Frederiksen, Christian Munk, Adriaan van den Brule, Edith Svare, Chris Meijer, Attilla Lorincz, Thomas Iftner
雑誌名: Cancer Res. 2006 Nov 1;66(21):10630-6. doi: 10.1158/0008-5472.CAN-06-1057. Epub 2006 Oct 23.
Abstract/Text In spite of the success of cervical cytology as a cancer-screening tool, it has important limitations, and human papillomavirus (HPV) testing may be valuable in future screening. The majority of women in screened populations, who test HPV positive, will have a concurrent normal smear, and we need more information about the risk for subsequent high-grade cervical lesions in these women. We examined 8,656 younger women (22-32 years old) and 1,578 older women (40-50 years old) who were followed for development of cervical neoplasia (cytology and/or histology) through the Danish Pathology Data Bank. We estimated the proportion of women developing cervical lesions of different types before a given time point as a function of time. Among women with normal cytology and positive high-risk Hybrid Capture 2 (HC2) test, 17.7% and 24.5% of younger and older women, respectively, had a subsequent abnormal Pap smear within 5 years. The risk of CIN3 or cancer within 10 years among younger women with positive HC2 test was 13.6% (10.9-16.2) and 21.2% (2.7-36.1) among older women. An analysis among younger women also being HC2-positive 2 years before baseline showed a subsequent 10-year risk of > or =CIN3 of 18% (14.6-21.5). Among older women where HPV may be added to general screening, the estimated absolute risk of > or =CIN3 in HC2-positive women was more than 20% within 10 years. These results indicate that even a single positive HPV test in cytologically negative women is substantially predictive of high-grade CIN and suggest that HC2 testing can help stratify women into different risk categories.

PMID 17062559  Cancer Res. 2006 Nov 1;66(21):10630-6. doi: 10.1158/000・・・
著者: Michelle J Khan, Philip E Castle, Attila T Lorincz, Sholom Wacholder, Mark Sherman, David R Scott, Brenda B Rush, Andrew G Glass, Mark Schiffman
雑誌名: J Natl Cancer Inst. 2005 Jul 20;97(14):1072-9. doi: 10.1093/jnci/dji187.
Abstract/Text BACKGROUND: Human papillomavirus (HPV) types 16 and 18 cause 60%-70% of cervical cancer worldwide, and other HPV types cause virtually all remaining cases. Pooled HPV testing for 13 oncogenic types, including HPV16 and 18, is currently used in clinical practice for triage of equivocal cytology and, in conjunction with Pap tests, is an option for general screening among women 30 years of age and older. It is not clear to what extent individual identification of HPV16 or HPV18 as an adjunct to pooled oncogenic HPV testing might effectively identify women at particularly high risk of cervical cancer or its immediate precursor, cervical intraepithelial neoplasia 3 (CIN3).
METHODS: From April 1, 1989, to November 2, 1990, a total of 20 810 women in the Kaiser Permanente health plan in Portland, OR, enrolled in a cohort study of HPV and cervical neoplasia. Women were tested for 13 oncogenic HPV types by Hybrid Capture 2 (HC2), and those women with a positive HC2 test were tested for HPV16 and 18. Enrollment Pap smear interpretation and HPV test results were linked to histologically confirmed CIN3 and cervical cancer (> or = CIN3) occurring during 10 years of cytologic follow-up. We calculated cumulative incidence rates with 95% confidence intervals for each interval up to 122 months using Kaplan-Meier methods.
RESULTS: The 10-year cumulative incidence rates of > or = CIN3 were 17.2% (95% confidence interval [CI] = 11.5% to 22.9%) among HPV16+ women and 13.6% (95% CI = 3.6% to 23.7%) among HPV18+ (HPV16-) women, but only 3.0% (95% CI = 1.9% to 4.2%) among HC2+ women negative for HPV16 or HPV18. The 10-year cumulative incidence among HC2- women was 0.8% (95% CI = 0.6% to 1.1%). A subanalysis among women 30 years of age and older with normal cytology at enrollment strengthened the observed risk differences.
CONCLUSIONS: HPV screening that distinguishes HPV16 and HPV18 from other oncogenic HPV types may identify women at the greatest risk of > or = CIN3 and may permit less aggressive management of other women with oncogenic HPV infections.

PMID 16030305  J Natl Cancer Inst. 2005 Jul 20;97(14):1072-9. doi: 10.・・・
著者: J Thomas Cox, Mark Schiffman, Diane Solomon, ASCUS-LSIL Triage Study (ALTS) Group
雑誌名: Am J Obstet Gynecol. 2003 Jun;188(6):1406-12.
Abstract/Text OBJECTIVE: The purpose of this study was to determine the risk of cumulative cervical intraepithelial neoplasia (CIN) grade 2 or 3 according to initial colposcopy and directed biopsy results among women with low-grade squamous intraepithelial lesions (LSIL) or human papillomavirus (HPV) DNA positive atypical squamous cells of undetermined significance (ASCUS).
STUDY DESIGN: A 2-year follow-up of 897 cases of LSIL and 1193 cases of HPV DNA positive ASCUS from the ASCUS/LSIL Triage Study was used to simulate American Society for Colposcopy and Cervical Pathology Consensus Conference recommendations. Women with CIN grade 1 or less were followed up for 2 years by semiannual cytologic examination, with universal exit colposcopy. The clinical end point was a cumulative clinical center histologic diagnosis of CIN grade 2 or 3.
RESULTS: The cumulative risk of CIN grade 2 or 3 was equivalent for LSIL (27.6%) and HPV positive ASCUS (26.7%). After excluding the women with a diagnosis of CIN grade 2 or 3 at initial colposcopy and directed biopsy (17.9%), the remaining women were at nearly identical risk for subsequent CIN grade 2 or 3 regardless of initial colposcopy result (completely negative colposcopy-11.3%; negative colposcopically directed biopsy-11.7%; and CIN grade 1 biopsy-13.0%).
CONCLUSION: LSIL and HPV positive ASCUS are clinically equivalent. Initial colposcopic detection of obviously prevalent CIN grade 2 or 3 reduces risk. However, for the remaining women who have CIN grade 1 or less on colposcopy and directed biopsy, the risk for subsequent CIN grade 2 or 3 (whether missed, prevalent, or truly incident) is approximately 12% over 2 years. This risk does not vary meaningfully by initial distinction of histologic CIN grade 1 from negative colposcopy and biopsy.

PMID 12824970  Am J Obstet Gynecol. 2003 Jun;188(6):1406-12.
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/・・・
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: Shiho Miura, Koji Matsumoto, Akinori Oki, Toyomi Satoh, Hajime Tsunoda, Toshiharu Yasugi, Yuji Taketani, Hiroyuki Yoshikawa
雑誌名: Int J Cancer. 2006 Dec 1;119(11):2713-5. doi: 10.1002/ijc.22195.
Abstract/Text
PMID 16929495  Int J Cancer. 2006 Dec 1;119(11):2713-5. doi: 10.1002/i・・・
著者: Masatoshi Yokoyama, Tsuyoshi Iwasaka, Chisato Nagata, Shiro Nozawa, Soei Sekiya, Yasuo Hirai, Koji Kanazawa, Shinji Sato, Hiroshi Hoshiai, Motoyasu Sugase, Takashi Kawana, Hiroyuki Yoshikawa
雑誌名: Cancer Lett. 2003 Mar 31;192(2):171-9.
Abstract/Text One hundred and eighty-five Japanese women with cervical intraepithelial neoplasia (CIN) were enrolled in this follow-up study. On the basis of the prevalence of human papillomavirus (HPV) DNA in Japanese cervical cancer patients, HPV types were categorized into three groups as follows: (1) high risk (types 16, 18, 33, 52, and 58), (2) intermediate risk (types 31, 35, 39, 51, 56, 59, 68, and 70), (3) low risk (type 6, 30, 42, 53, 54, 55, 66 and unclassified types). High-risk HPV infection was a risk factor for progression of the disease. The regression rate in the HPV negative group was higher (83.3%) than those in the HPV positive groups, but the differences in regression were no longer significant after adjustment for age and CIN grade. It is also noted that a lower cytomegalovirus IgG level and a smaller number of past pregnancies might be associated with the regression of CIN lesions.

PMID 12668281  Cancer Lett. 2003 Mar 31;192(2):171-9.

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