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1. Ruffin MT, Bailey JM, Normolle DP, Michael CW, Bieniasz ME, Kmak DC, Unger ER, Brenner DE: Low-dose topical delivery of all-trans retinoic acid for cervical intraepithelial neoplasia II and III. Cancer Epidemiol Biomarkers Prev; 2004 Dec;13(12):2148-52
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Low-dose topical delivery of all-trans retinoic acid for cervical intraepithelial neoplasia II and III.
  • OBJECTIVE: The objective of this study was to determine an effective dose for all-trans retinoic acid (atRA) delivered with a cervical cap and sponge for 4 days to women with cervical intraepithelial neoplasia (CIN) II/III.
  • METHODS: Study participants made up of 175 women with biopsy-proven CIN II/III were randomized to four consecutive days of atRA at one of three doses (0.16%, 0.28%, and 0.36%) or placebo.
  • All subjects underwent a repeat colposcopy evaluation and biopsy of the cervix at 12 weeks.
  • Among participants, 93% were human papillomavirus-positive at baseline with 68% positive for high-risk types.
  • Participants with CIN II at baseline were more likely to be free of disease at 12 weeks than participants with CIN III at baseline (P = 0.003).
  • There were no reported systemic adverse events related to drug or placebo exposure and only mild local self-reported and clinician-detected toxicities.
  • CONCLUSION: Lower concentrations of atRA applied with a cervical cap for 4 days were no more effective than placebo.
  • However, the rate of histologic regression in biopsied CIN II/III patients was high even over a short time interval, and emphasizes the importance of having a placebo arm and an adequate sample size.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Antineoplastic Agents / therapeutic use. Cervical Intraepithelial Neoplasia / drug therapy. Tretinoin / administration & dosage. Tretinoin / therapeutic use. Uterine Cervical Neoplasms / prevention & control
  • [MeSH-minor] Adolescent. Adult. Chemoprevention. Colposcopy. Contraceptive Devices, Female. Dose-Response Relationship, Drug. Female. Humans. Middle Aged. Placebos. Risk Factors. Sample Size


2. TOMBOLA Group: Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial. BMJ; 2009 Jul 28;339:b2548
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  • [Title] Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial.
  • OBJECTIVES: To compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy.
  • DESIGN: Multicentre individually randomised controlled trial, nested within the NHS cervical screening programmes.
  • INTERVENTIONS: Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment (by large loop excision) if these showed cervical intraepithelial neoplasia grade II or III or worse.
  • MAIN OUTCOME MEASURES: Clinical end points: cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years.
  • RESULTS: 879 women (44%) had a normal transformation zone at colposcopy and had no further procedures at that time.
  • Of women randomised to biopsy and recall, 157 (16%) required a second clinic visit for treatment.
  • Specimens from almost 60% (n=296) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia (31%; n=156) or showed cervical intraepithelial neoplasia grade I (28%; n=140).
  • The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22% (n=216) in the biopsy and recall arm and 23% (n=228) in the immediate large loop excision arm.
  • There was no significant difference between the arms in cumulative incidence of cervical intraepithelial neoplasia grade II or worse (adjusted relative for risk large loop excision v biopsy 1.04, 95% confidence interval 0.86 to 1.25) or grade III or worse (1.03, 0.79 to 1.34).
  • A greater proportion of disease was detected at initial investigation and less during follow-up and at exit in the immediate large loop excision arm, but time of detection did not differ significantly between arms.
  • Higher proportions of women randomised to large loop excision reported moderate or more severe bleeding and discharge.
  • CONCLUSION: A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy.

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  • (PMID = 19638647.001).
  • [ISSN] 1756-1833
  • [Journal-full-title] BMJ (Clinical research ed.)
  • [ISO-abbreviation] BMJ
  • [Language] ENG
  • [Databank-accession-numbers] ISRCTN/ ISRCTN34841617
  • [Grant] United Kingdom / Medical Research Council / / G9700808
  • [Publication-type] Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC2718084
  • [Investigator] Cruickshank M; Murray G; Parkin D; Smart L; Walker E; Waugh N; Avis M; Chilvers C; Fielding K; Hammond R; Jenkins D; Johnson J; Neal K; Russell I; Seth R; Whynes D; Duncan I; Robertson A; Little J; Sharp L; Russell I; Walker L; Anthony B; Bell S; Bowie A; Brown K; Brown J; Chew K; Cochran C; Cotton S; Dean J; Dunn K; Edwards J; Evans D; Fenty J; Finlayson A; Gallagher M; Gray N; Heddle M; Innes A; Jobson D; Keillor M; MacGregor J; Mackenzie S; Mackie A; McPherson G; Okorocha I; Reilly M; Rodgers J; Thornton A; Yeats R; Alexander L; Buchanan L; Henderson S; Iterbeke T; Lucas S; Manderson G; Nicol S; Reid G; Robinson C; Sandilands T; Adrian M; Al-Sahab A; Bentley E; Brook H; Bushby C; Cannon R; Cooper B; Dowell R; Dunderdale M; Gabrawi; Guo L; Heideman L; Jones S; Lawson S; Philips Z; Platt C; Prabhakaran S; Rippin J; Thompson R; Williams E; Woolley C; Boroujerdi M; Cotton S; Harrild K; Norrie J; Day N; Marteau T; Parmar M; Patnick J; Woodman C; Altman D; Moss S; Wells M; Sharp L; Cruickshank M; Little J; Cotton S; Harrild K; Cochran C; Duncan I; Gray N; Hammond R; Smart L; Thornton A; Waugh N; Woolley C
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3. Follen M, Atkinson EN, Schottenfeld D, Malpica A, West L, Lippman S, Zou C, Hittelman WN, Lotan R, Hong WK: A randomized clinical trial of 4-hydroxyphenylretinamide for high-grade squamous intraepithelial lesions of the cervix. Clin Cancer Res; 2001 Nov;7(11):3356-65
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  • [Title] A randomized clinical trial of 4-hydroxyphenylretinamide for high-grade squamous intraepithelial lesions of the cervix.
  • PURPOSE: Previous trials of topical trans-retinoic acid treatment of cervical intraepithelial neoplasia (CIN) grades 2 and 3 led to a statistically significant regression of CIN 2, but not CIN 3.
  • We tested N-(4-hydroxyphenyl)retinamide (4-HPR), a promising oral retinoid that has been shown to induce apoptosis through nonretinoic receptor acid-mediated pathways, for its toxicity and efficacy against CIN 2/3.
  • EXPERIMENTAL DESIGN: In a blinded randomized trial, 4-HPR at 200 mg/day for 6 months (with a 3-day/month drug holiday) was compared with placebo in patients with biopsy-proven CIN-2/3 [high-grade squamous intraepithelial lesions (HGSILs)].
  • When the code was broken because of the poorer outcomes, we discovered that the 4-HPR treatment arm was performing more poorly than was the placebo at 6 and 12 months (25 versus 44% response rates at 6 months; 14 versus 50% at 12 months).
  • CONCLUSIONS: 4-HPR at 200 mg/day with a 3-day/month drug holiday is not active compared with placebo in the treatment of HGSIL.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Cervical Intraepithelial Neoplasia / drug therapy. Fenretinide / therapeutic use. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Cheilitis / chemically induced. Cross-Over Studies. Exanthema / chemically induced. Female. Humans. Medical Futility. Patient Compliance. Photosensitivity Disorders / chemically induced. Time Factors. Treatment Outcome

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  • (PMID = 11705848.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Randomized Controlled Trial
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 187EJ7QEXL / Fenretinide
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4. Van Pachterbeke C, Bucella D, Rozenberg S, Manigart Y, Gilles C, Larsimont D, Vanden Houte K, Reynders M, Snoeck R, Bossens M: Topical treatment of CIN 2+ by cidofovir: results of a phase II, double-blind, prospective, placebo-controlled study. Gynecol Oncol; 2009 Oct;115(1):69-74
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Topical treatment of CIN 2+ by cidofovir: results of a phase II, double-blind, prospective, placebo-controlled study.
  • OBJECTIVE: Randomized controlled trial evaluating a topical treatment for cervical intraepithelial neoplasia 2 and 3 (CIN 2+) using cidofovir.
  • METHODS: Fifty-three women with a biopsy-proven CIN 2+ were randomly assigned, 6 weeks before their planned conisation, either 3 applications of 3 ml 2% cidofovir in Intrasite gel in a cervical cap or a placebo (the same volume of Intrasite alone).
  • A cervical sample for high-risk types of human papillomaviruses (HPV) (Hybrid Capture 2 or HC2) was taken before treatment and before conisation.
  • Fourteen of the 23 cones were free of any CIN (60.8%) in the cidofovir group.
  • Only 5 of 25 cones were free of any CIN (20%) in the placebo group (p<0.01).
  • CONCLUSION: The medical topical treatment with cidofovir, at this point, cannot replace conisation, but it is a promising candidate for topical chemotherapy of CIN 2+ lesions; a larger prospective randomized study is needed to confirm our results.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Cervical Intraepithelial Neoplasia / drug therapy. Cytosine / analogs & derivatives. Organophosphonates / administration & dosage. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Administration, Topical. Adult. Combined Modality Therapy. Conization. Contraceptive Devices, Female. Double-Blind Method. Female. Gels / administration & dosage. Humans. Papillomavirus Infections / pathology. Papillomavirus Infections / virology. Placebos. Prospective Studies


5. Di Roma E, Parlavecchio E, Vettraino G, Corosu R: [CIN: multicentric study of therapeutic strategies]. Minerva Ginecol; 2001 Dec;53(6):379-2
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [CIN: multicentric study of therapeutic strategies].
  • [Transliterated title] CIN: studio multicentrico sulle strategie terapeutiche.
  • BACKGROUND: Cervical Intraepithelial Neoplasia (CIN) is a dysplastic lesion that precedes cervical cancer.
  • The diagnosis is made by colposcopic, cytologic and bioptic exams.
  • Therapy may be physical, pharmacological or surgical.
  • Our aim was to evaluate their therapeutic strategies for CIN and cervical condylomata.
  • We referred to SIGO 1999 guidelines for CIN therapy and to European guidelines for cervical condylomata therapy.
  • RESULTS: The centers used drugs more for HPV infections (57%) than for dysplasia (33%).
  • Drug therapy was used more in the past (66.67%).
  • Actually they prefer treating CIN I with electrocoagulation diathermy (DTC), CIN II with loop electrosurgical excision procedures (LEEP) or Laser, CIN III with cold knife conization or LEEP, cervical condylomata with laser or DTC.
  • CONCLUSIONS: The results show that the centers prefer physical therapy.
  • Therapeutic strategies comply with SIGO 1999 guidelines for therapy of CIN and with European guidelines for cervical condylomata partially.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / therapy. Uterine Cervical Neoplasms / therapy
  • [MeSH-minor] Conization. Electrocoagulation. Electrosurgery. Female. Humans. Hysterectomy. Interferons / therapeutic use. Interviews as Topic. Italy. Laser Therapy. Practice Guidelines as Topic. Surveys and Questionnaires

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  • (PMID = 11723421.001).
  • [ISSN] 0026-4784
  • [Journal-full-title] Minerva ginecologica
  • [ISO-abbreviation] Minerva Ginecol
  • [Language] ita
  • [Publication-type] Comparative Study; English Abstract; Journal Article; Multicenter Study
  • [Publication-country] Italy
  • [Chemical-registry-number] 9008-11-1 / Interferons
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6. Corona Gutierrez CM, Tinoco A, Navarro T, Contreras ML, Cortes RR, Calzado P, Reyes L, Posternak R, Morosoli G, Verde ML, Rosales R: Therapeutic vaccination with MVA E2 can eliminate precancerous lesions (CIN 1, CIN 2, and CIN 3) associated with infection by oncogenic human papillomavirus. Hum Gene Ther; 2004 May;15(5):421-31
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Therapeutic vaccination with MVA E2 can eliminate precancerous lesions (CIN 1, CIN 2, and CIN 3) associated with infection by oncogenic human papillomavirus.
  • Human papillomavirus (HPV) infection is associated with cervical cancer.
  • Cervical cancer is a serious problem in developing countries because it is usually not detected at an early stage.
  • In a phase I/II clinical trial, we evaluated the potential use of the MVA E2 recombinant vaccinia virus to treat cervical intraepithelial neoplasia CIN 1, CIN 2, and CIN 3 lesions associated with human papillomavirus (HPV) infection.
  • Seventy-eight women with CIN 1-, CIN 2-, and CIN 3-grade lesions were treated with either an MVA E2 recombinant virus vaccine or with cryosurgery.
  • The type of immune response after MVA E2 injection was determined by measuring antibody titers against MVA E2 virus and the E2 protein, and by the presence of cytotoxic activity against cancer cells bearing papillomavirus DNA.
  • Thirty-four of 36 patients showed complete elimination of precancerous lesions after treatment with the MVA E2 vaccine.
  • In two patients, precancerous lesions were reduced from grade CIN 3 to CIN 1.
  • Three other patients presented isolated koilocytes after treatment with MVA E2.
  • Colposcopy revealed no lesions in 85% of patients, and only small aceto-white spots were detected in 15% of patients after treatment with MVA E2.
  • All patients developed antibodies against the MVA E2 vaccine, and vaccination generated a specific cytotoxic response against HPV-transformed cells.
  • Furthermore, 50% of patients showed no evidence of papillomavirus after treatment with MVA E2, while the remaining 50% showed persistence of HPV DNA, but at approximately only 10% of the original viral load.
  • Cryosurgery eliminated the lesions of CIN 1 in all patients, but patients so treated did not develop cytotoxic activity against cancer cells.
  • These results show that therapeutic vaccination with MVA E2 vaccine is an excellent prospective means for stimulating the immune system and causing the regression of precancerous CIN 1, CIN 2, and CIN 3 lesions when the vaccine is given locally.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / drug therapy. Uterine Cervical Neoplasms / prevention & control. Vaccines, DNA / therapeutic use. Vaccinia virus / immunology
  • [MeSH-minor] Adult. Cell Transformation, Viral. Colposcopy. Cytotoxicity Tests, Immunologic. Enzyme-Linked Immunosorbent Assay. Female. Humans. Middle Aged. Papillomaviridae / immunology. Papillomavirus Infections / blood. Patient Selection. Treatment Outcome. Viral Load

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  • (PMID = 15144573.001).
  • [ISSN] 1043-0342
  • [Journal-full-title] Human gene therapy
  • [ISO-abbreviation] Hum. Gene Ther.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Vaccines, DNA
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7. Keefe KA, Schell MJ, Brewer C, McHale M, Brewster W, Chapman JA, Rose GS, McMeeken DS, Lagerberg W, Peng YM, Wilczynski SP, Anton-Culver H, Meyskens FL, Berman ML: A randomized, double blind, Phase III trial using oral beta-carotene supplementation for women with high-grade cervical intraepithelial neoplasia. Cancer Epidemiol Biomarkers Prev; 2001 Oct;10(10):1029-35
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] A randomized, double blind, Phase III trial using oral beta-carotene supplementation for women with high-grade cervical intraepithelial neoplasia.
  • To evaluate the effect of daily beta-carotene (30 mg) versus placebo over a 2-year period on cervical intraepithelial neoplasia (CIN) 2 and 3 lesions.
  • Variables that influence the risk of HPV infection and CIN, such as cigarette smoking and sexual behavior, were evaluated.
  • Cervical biopsies were performed before treatment and after 6 and 24 months to evaluate response.
  • Persistence of or progression to CIN 3 resulted in removal from the study, whereas treatment continued for 2 years on all others.
  • The presence and type of HPV was determined by PCR.
  • Response was defined as an improvement in CIN by 2 grades.
  • Mantel-Haenszel chi(2) test was used to analyze response to treatment.
  • Fisher's exact test was used to determine the effect of HPV and CIN grade on response Wilcoxon's rank-sum tests were used to compare micronutrient levels between groups.
  • Twenty-one of 124 enrolled women were not randomized because they either moved, became pregnant, voluntarily withdrew, or the pathological review of their initial cervical biopsies did not confirm CIN 2 or 3.
  • The overall regression rate (32%) was similar between treatment arms and when stratified for CIN grade.
  • CIN regression was negatively correlated with retinol levels.
  • In conclusion, beta-carotene does not enhance the regression of high-grade CIN, especially in HPV-positive subjects.
  • [MeSH-major] Antioxidants / administration & dosage. Cervical Intraepithelial Neoplasia / drug therapy. Uterine Cervical Neoplasms / drug therapy. beta Carotene / administration & dosage
  • [MeSH-minor] Administration, Oral. Adolescent. Adult. Biopsy, Needle. Dietary Supplements. Double-Blind Method. Drug Administration Schedule. Female. Follow-Up Studies. Humans. Logistic Models. Long-Term Care. Middle Aged. Probability. Reference Values. Severity of Illness Index. Treatment Outcome. Vaginal Smears


8. Keefe KA, Tadir Y, Tromberg B, Berns M, Osann K, Hashad R, Monk BJ: Photodynamic therapy of high-grade cervical intraepithelial neoplasia with 5-aminolevulinic acid. Lasers Surg Med; 2002;31(4):289-93
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Photodynamic therapy of high-grade cervical intraepithelial neoplasia with 5-aminolevulinic acid.
  • BACKGROUND AND OBJECTIVES: To determine the safety and efficacy of 5-aminolevulinic acid (ALA) as a topically applied photosensitizer for photodynamic therapy (PDT) of cervical intraepithelial neoplasia (CIN).
  • STUDY DESIGNS/MATERIALS AND METHODS: Forty women, who were at least 18 years old with persistent biopsy-proven CIN 2 and CIN 3 within the previous 3 months of enrollment, underwent PDT in a phase I and II design.
  • ALA was placed in a cervical cap fitted to the cervix.
  • Success was defined as the absence of CIN on Pap smear or colposcopic examination at 12-months.
  • Sixty percent had CIN 3 and 40% CIN 2.
  • Three patients progressed from CIN 2 to CIN 3.
  • CONCLUSIONS: PDT at this light and ALA dose is well tolerated but has minimal activity in the treatment of CIN 2 and CIN 3.
  • [MeSH-major] Aminolevulinic Acid / therapeutic use. Cervical Intraepithelial Neoplasia / drug therapy. Photochemotherapy / adverse effects. Photosensitizing Agents / therapeutic use. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Female. Follow-Up Studies. Humans. Outcome Assessment (Health Care). Severity of Illness Index. Time Factors

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  • [Copyright] Copyright 2002 Wiley-Liss, Inc.
  • (PMID = 12355576.001).
  • [ISSN] 0196-8092
  • [Journal-full-title] Lasers in surgery and medicine
  • [ISO-abbreviation] Lasers Surg Med
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / 1K23CA87558; United States / NCI NIH HHS / CA / CA-32248
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Photosensitizing Agents; 88755TAZ87 / Aminolevulinic Acid
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9. Hefler LA, Grimm C, Speiser P, Sliutz G, Reinthaller A: The cyclooxygenase-2 inhibitor rofecoxib (Vioxx) in the treatment of cervical dysplasia grade II-III A phase II trial. Eur J Obstet Gynecol Reprod Biol; 2006 Apr 1;125(2):251-4
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The cyclooxygenase-2 inhibitor rofecoxib (Vioxx) in the treatment of cervical dysplasia grade II-III A phase II trial.
  • OBJECTIVE: To determine whether the cyclooxygenase (COX)-2 inhibitor rofecoxib increases the regression rates of cervical intraepithelial neoplasia (CIN) grade II and III.
  • STUDY DESIGN: A prospective, randomized, placebo-controlled, double-blind study with rofecoxib 25 mg daily for 6 [corrected] months as active treatment for patients with CIN II and III was started in May 2004 [corrected] and was halted after rofecoxib withdrawal in October 2004 [corrected] RESULTS: A total of 16 patients with CIN II (n=9) and CIN III (n=7) were included in our study.
  • Regression rates in the rofecoxib and placebo arm were statistically not significant (25% versus 12.5%) after a mean of 87 (46.3) days of treatment.
  • No severe side effects were noted during the therapy; no dropouts were recorded.
  • CONCLUSION: A conservative treatment of CIN II and III is feasible.
  • Inhibitors of COX, especially COX-2, were seen as candidates for cancer chemoprevention.
  • The results obtained should be added to those already published for planning future studies on medical therapies for high grade CIN.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / drug therapy. Cyclooxygenase 2 Inhibitors / therapeutic use. Lactones / therapeutic use. Sulfones / therapeutic use. Uterine Cervical Dysplasia / drug therapy

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  • [ErratumIn] Eur J Obstet Gynecol Reprod Biol. 2006 Nov;129(1):100
  • (PMID = 16188370.001).
  • [ISSN] 0301-2115
  • [Journal-full-title] European journal of obstetrics, gynecology, and reproductive biology
  • [ISO-abbreviation] Eur. J. Obstet. Gynecol. Reprod. Biol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial
  • [Publication-country] Ireland
  • [Chemical-registry-number] 0 / Cyclooxygenase 2 Inhibitors; 0 / Lactones; 0 / Sulfones; 0QTW8Z7MCR / rofecoxib
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10. Sikorski M, Zrubek H: Long-term follow-up of patients treated with recombinant human interferon gamma for cervical intraepithelial neoplasia. Int J Gynaecol Obstet; 2003 Aug;82(2):179-85
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Long-term follow-up of patients treated with recombinant human interferon gamma for cervical intraepithelial neoplasia.
  • OBJECTIVES: The immediate results of interferon gamma (IFN-gamma) treatment in the management of cervical intraepithelial neoplasia (CIN) have been described.
  • However, little is known of the long-term results of this conservative treatment and we aimed to assess them.
  • METHODS: We conducted a 5-year follow-up of 13 women with either complete response to intracervical administration of 6,000,000 IU of IFN-gamma (remission from human papilloma virus-induced CIN occurred in nine cases) or partial response (a lower grade of CIN and/or HPV clearance was achieved in four cases).
  • We found three cases of relapse of stage 1 CIN (CIN I), for a recurrence rate of 33.3%, and three cases of complete remission in four subjects with initial diagnosis of partial response.
  • This allowed us to assess the overall lesion-free rate at 53% for the entire group of patients who had CIN I and CIN II treated with IFN-gamma.
  • CONCLUSIONS: Immunomodulation therapy with IFN-gamma has a high long-term efficacy; however, it is inferior to that of surgery.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Cervical Intraepithelial Neoplasia / drug therapy. Interferon-gamma / therapeutic use. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Colposcopes. Female. Follow-Up Studies. Humans. Middle Aged. Papanicolaou Test. Recombinant Proteins. Treatment Outcome. Vaginal Smears

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  • (PMID = 12873779.001).
  • [ISSN] 0020-7292
  • [Journal-full-title] International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics
  • [ISO-abbreviation] Int J Gynaecol Obstet
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Recombinant Proteins; 82115-62-6 / Interferon-gamma
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11. Orbell S, Hagger M, Brown V, Tidy J: Appraisal theory and emotional sequelae of first visit to colposcopy following an abnormal cervical screening result. Br J Health Psychol; 2004 Nov;9(Pt 4):533-55
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Appraisal theory and emotional sequelae of first visit to colposcopy following an abnormal cervical screening result.
  • OBJECTIVES: Attendance at colposcopy following an abnormal cervical smear is potentially a highly distressing event.
  • We also compare the psychological sequelae of immediate treatment at first colposcopy (See and Treat, ST) vs. colposcopy with treatment deferred to a later date (Diagnose and Defer, DD).
  • RESULTS: Diagnosis and cognitive appraisals were each significantly associated with emotion, together accounting for between 3 and 15% of variance in different emotions.
  • Women with Cervical Intraepithelial Neoplasia (CIN) 2 or CIN 3 undergoing 'ST' were less anxious, less embarrassed and significantly more relieved compared with a matched sample of women undergoing 'DT', and perceived their first appointment as more motivationally congruent.
  • CONCLUSION: Diagnosis, motivationally incongruent experiences and low emotion-focused coping potential are the most important determinants of anxiety after colposcopy.
  • [MeSH-major] Affect. Attitude to Health. Colposcopy / psychology. Office Visits. Psychological Theory. Uterine Cervical Neoplasms / diagnosis. Uterine Cervical Neoplasms / epidemiology
  • [MeSH-minor] Adolescent. Adult. Aged. Cognition. Female. Humans. Middle Aged. Surveys and Questionnaires. Time Factors


12. Kietpeerakool C, Srisomboon J: Medical treatment of cervical intraepithelial neoplasia II, III: an update review. Int J Clin Oncol; 2009 Feb;14(1):37-42
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  • [Title] Medical treatment of cervical intraepithelial neoplasia II, III: an update review.
  • Cervical intraepithelial neoplasia (CIN) II, III is a preinvasive stage of squamous cell carcinoma of the uterine cervix.
  • The standard treatment for CIN II, III consists of ablation and excision.
  • However, nonsurgical treatment may be necessary for some women to preserve future reproductive potential.
  • This review was conducted to summarize available published data on the efficacy and safety of medical treatment for CIN II, III.
  • Based on existing studies, cyclooxygenase (COX)-2 inhibitors; indole-3-carbinol; and novel immunotherapy agents, including ZYC101a, MVA E2, and HspE7, have been observed as possessing therapeutic activity without any major treatment-related complications.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Cancer Vaccines / therapeutic use. Cervical Intraepithelial Neoplasia / therapy. Genetic Therapy. Immunotherapy. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Female. Humans. Neoplasm Staging. Treatment Outcome


13. Garcia F, Petry KU, Muderspach L, Gold MA, Braly P, Crum CP, Magill M, Silverman M, Urban RG, Hedley ML, Beach KJ: ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol; 2004 Feb;103(2):317-26
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  • [Title] ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial.
  • OBJECTIVE: The objective of this study was to assess the safety and efficacy of a novel therapeutic, ZYC101a, for the treatment of women with histologically confirmed cervical intraepithelial neoplasia (CIN) 2/3.
  • METHODS: A multicenter, double-blind, randomized, placebo-controlled trial was conducted in a group of women with biopsy-confirmed CIN 2/3.
  • Six months after the first injection, subjects underwent cervical conization.
  • The primary endpoint for this study was histologically confirmed resolution of CIN 2/3.
  • RESULTS: The most common adverse events were related to the injection site, were mild to moderate, and did not worsen at later treatments.
  • CONCLUSIONS: ZYC101a was shown to be well tolerated in all patients and to promote the resolution of CIN 2/3 in women younger than 25 years.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Cervical Intraepithelial Neoplasia / drug therapy. Cervical Intraepithelial Neoplasia / pathology. DNA / therapeutic use. Uterine Cervical Neoplasms / drug therapy. Uterine Cervical Neoplasms / pathology
  • [MeSH-minor] Adolescent. Adult. Dose-Response Relationship, Drug. Double-Blind Method. Drug Administration Schedule. Drug Combinations. Female. Follow-Up Studies. Humans. Injections, Intramuscular. Middle Aged. Neoplasm Staging. Oncogene Proteins, Viral / administration & dosage. Probability. Reference Values. Risk Assessment. Treatment Outcome. Viral Proteins / administration & dosage


14. Ruan YH, Wei WL, Zhang HX, Liang ZN, Liu BY, Chen Y: [Comparison and analysis of expression of c-myc and p16 in cervical carcinoma]. Ai Zheng; 2003 Jun;22(6):602-6
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  • [Title] [Comparison and analysis of expression of c-myc and p16 in cervical carcinoma].
  • It is still unclear whether abnormal expression of c-myc and p16 cooperate in the occurrence and progression of cervical carcinoma, and whether there exists a connection between the expression of two genes and the chemotherapy response of cervical carcinoma.
  • This study was designed to investigate the correlation between the expression of c-myc and p16 and their roles in the genesis and development of the uterine cervical carcinoma and chemotherapy response.
  • METHODS: Using in situ hybridization, 37 cases of cervical carcinoma (including 11 cases after chemotherapy), 21 cases of precancerous lesion and 5 cases of normal cervix were observed for c-myc and p16 mRNA with dig-labeled probes.
  • RESULTS: The positive expression rates of p16 in normal cervix,CIN (cervical intraepithelial neoplasia) and cervical carcinoma were 100%, 71.4%, and 21.6%, respectively (P=0.0001), whereas the expression rates of c-myc were 0%, 42.9%, and 75.7% (P=0.0011), respectively.
  • The expression of positive signals of c-myc increased with the increase of malignant degree, and the positive signals in CIN III were also higher than that in CIN II and CIN I.
  • The expression rates of c-myc were decreased in cervical carcinoma after chemotherapy.
  • There was a tendency of negative correlation between the expression of c-myc and p16(r(s)=-0.907).
  • Expression of p16 and c-myc showed no significant difference between effectual and ineffectual chemotherapy groups.
  • CONCLUSION: Both over expression of c-myc and descended expression of p16 may play an important role in the genesis and development of uterine cervical carcinoma.
  • The increased expression of c-myc in different grade CIN suggests that carcinogenesis of cervix be progressive.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / genetics. Genes, myc. Uterine Cervical Neoplasms / genetics
  • [MeSH-minor] Female. Genes, p16. Humans. Neoplasm Staging. RNA, Messenger / analysis

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  • (PMID = 12948409.001).
  • [Journal-full-title] Ai zheng = Aizheng = Chinese journal of cancer
  • [ISO-abbreviation] Ai Zheng
  • [Language] chi
  • [Publication-type] Comparative Study; English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 0 / RNA, Messenger
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15. Snoeck R, Noel JC, Muller C, De Clercq E, Bossens M: Cidofovir, a new approach for the treatment of cervix intraepithelial neoplasia grade III (CIN III). J Med Virol; 2000 Feb;60(2):205-9
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  • [Title] Cidofovir, a new approach for the treatment of cervix intraepithelial neoplasia grade III (CIN III).
  • Cervix intraepithelial neoplasia grade III (CIN III) is an intraepithelial proliferative process with different levels of severity depending on both the extension of the proliferation in the epithelium and the presence of cellular atypia.
  • The results of a preliminary study are described on the local application of cidofovir, an acyclic nucleoside phosphonate derivative with broad-spectrum anti-DNA virus activity for the treatment of CIN III.
  • Cidofovir 1% in gel was applied three times, every other day, on the cervix of each of 15 women with biopsy proven CIN III.
  • Within 1 month after the start of treatment, the cervix was removed surgically.
  • In 7 of the 15 patients the histology showed a complete response, whereas 5 patients had a partial response characterized by the persistence of CIN II-III lesions, 1 patient had a dysplasia of lower grade (CIN I), and 2 patients did not show differences in the histology.
  • Cidofovir 1% gel was able to inhibit partially or completely cervical dysplasia lesions after only three applications (every other day).
  • This effect was specific and tissue other than the dysplastic epithelium was not affected by the treatment.
  • [MeSH-major] Antiviral Agents / therapeutic use. Cervical Intraepithelial Neoplasia / drug therapy. Cytosine / analogs & derivatives. Organophosphonates. Organophosphorus Compounds / therapeutic use. Papillomavirus Infections / drug therapy. Tumor Virus Infections / drug therapy. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Biopsy. Cervix Uteri / pathology. Cervix Uteri / surgery. Cervix Uteri / virology. Conization. Female. Humans. Immunohistochemistry. Middle Aged. Papillomaviridae / drug effects. Papillomaviridae / isolation & purification. Polymerase Chain Reaction

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  • [Copyright] Copyright 2000 Wiley-Liss, Inc.
  • (PMID = 10596022.001).
  • [ISSN] 0146-6615
  • [Journal-full-title] Journal of medical virology
  • [ISO-abbreviation] J. Med. Virol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / Organophosphonates; 0 / Organophosphorus Compounds; 8J337D1HZY / Cytosine; JIL713Q00N / cidofovir
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16. Sikorski M, Zrubek H: Recombinant human interferon gamma in the treatment of cervical intraepithelial neoplasia (CIN) associated with human papillomavirus (HPV) infection. Eur J Gynaecol Oncol; 2003;24(2):147-50
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  • [Title] Recombinant human interferon gamma in the treatment of cervical intraepithelial neoplasia (CIN) associated with human papillomavirus (HPV) infection.
  • Human papillomavirus (HPV) proteins E6 & E7 are considered to be the constitutively expressed neoantigens in a vast majority of cervical squamous intraepithelial lesions and cancers.
  • In order to study this effect in vivo we undertook a trial in which 20 women with a definite diagnosis of cervical intraepithelial neoplasia (CIN) grade I or II with coexistent high-risk HPV infection (detected by the Hybrid Capture System) underwent four months observation followed by intracervical administration of INFgamma in cases without spontaneous regression (17 cases).
  • Human recombinant interferon gamma 1-b (Imukin) was administered intracervically four times in equal doses in two-day intervals to a total dose of 6,000,000 IU.
  • The results of therapy were verified by punch biopsy evaluation and HPV-DNA testing two months after completion, and revealed a complete response in nine women (complete regression of CIN and remission of HPV infection in 53% of treated cases) and partial response in four cases (lower grade of CIN or/and remission of HPV infection--23.5%).
  • The differences between spontaneous (before treatment) and treatment-related regressions were significant at p < 0.05.
  • We conclude that in selected cases (mainly young women who have not completed their procreation and are compliant with the therapy) a conservative approach to CIN management with intracervical IFNgamma injections seems to be a valuable method.
  • [MeSH-major] Antiviral Agents / therapeutic use. Cervical Intraepithelial Neoplasia / drug therapy. Interferon-gamma / therapeutic use. Papillomaviridae. Papillomavirus Infections / drug therapy. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Female. Humans. Middle Aged. Prospective Studies. Recombinant Proteins. Treatment Outcome. Vaginal Smears

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  • (PMID = 12701965.001).
  • [ISSN] 0392-2936
  • [Journal-full-title] European journal of gynaecological oncology
  • [ISO-abbreviation] Eur. J. Gynaecol. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / Recombinant Proteins; 82115-62-6 / Interferon-gamma
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17. Wang J, Xu J, Chen J, He Q, Xiang L, Huang X, Ding G, Xu S: Successful photodynamic therapy with topical 5-aminolevulinic acid for five cases of cervical intraepithelial neoplasia. Arch Gynecol Obstet; 2010 Sep;282(3):307-12
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  • [Title] Successful photodynamic therapy with topical 5-aminolevulinic acid for five cases of cervical intraepithelial neoplasia.
  • OBJECTIVES: Photodynamic therapy (PDT) is a minimally invasive treatment for cervical intraepithelial neoplasia.
  • The purpose of this study was to assess the feasibility and effectiveness of PDT in patients with CIN and high-risk HPV infection.
  • METHODS: Five patients diagnosed CIN 2 or CIN 3 with human papillomavirus (HPV) infection were included.
  • Each patient had gynecologic examination including cervical cytology, HPV DNA testing, colposcopy and biopsy.
  • Two grams of 5-aminolevulinic acid (ALA) gel (118 mg/g) was topically applied to the cervix and covered with a special plastic cap for 3-4 h, followed by 20 min illumination of both ecto- and endo-cervical canal with red coherent light (wavelength 633 nm) using a PDT laser and a special light catheter.
  • The PDT therapy was repeated with an interval of 1 week.
  • RESULTS: Treatment could be accomplished in all cases and no severe side effect was encountered.
  • All the CIN2 patients had a complete response for 9 months and one CIN3 HPV remained positive for 6 months after three or four treatments.
  • CONCLUSION: PDT seems to be a non-invasive, repeatable procedure for CIN and cervical HPV infection with minimal side effects and can be easily performed on outpatient basis.
  • [MeSH-major] Aminolevulinic Acid / administration & dosage. Cervical Intraepithelial Neoplasia / drug therapy. Papillomavirus Infections / drug therapy. Photochemotherapy. Photosensitizing Agents / administration & dosage. Uterine Cervical Neoplasms / drug therapy


18. Paulino AC, Wen BC, Brown CK, Tannous R, Mayr NA, Zhen WK, Weidner GJ, Hussey DH: Late effects in children treated with radiation therapy for Wilms' tumor. Int J Radiat Oncol Biol Phys; 2000 Mar 15;46(5):1239-46
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  • [Title] Late effects in children treated with radiation therapy for Wilms' tumor.
  • PURPOSE: To determine the frequency and types of late effects in children receiving radiation therapy (RT) for Wilms' tumor.
  • MATERIALS AND METHODS: From 1968 to 1994, 55 children received megavoltage RT at our institution as part of treatment for Wilms' tumor.
  • There were 25 female and 17 male patients with a median age at diagnosis of 48 months (range, 7-126 months).
  • There were 12 Stage I, eight Stage II, 15 Stage III, six Stage IV, and one Stage V patient.
  • Whole-lung RT was delivered to 13 patients either at diagnosis or pulmonary relapse.
  • All patients received chemotherapy; the most common agents were actinomycin-D/vincristine/adriamycin in 13 and actinomycin-D/vincristine in 18.
  • RESULTS: Of 42 patients, 13 (31.0%) did not have late effects of treatment.
  • The number of patients who developed muscular hypoplasia, limb length inequality, kyphosis, and iliac wing hypoplasia were seven (16.7%), five (11.9%), three (7.1%), and three (7.1%), respectively.
  • Median time to development of scoliosis was 102 months, with a range of 16-146 months.
  • Only one of 12 Group A patients developed scoliosis.
  • Of 23 patients, five irradiated within 10 days of surgery and one of 19 irradiated after 10 days developed bowel obstruction (p = 0.09, log rank test).
  • Three patients developed hypertension with normal blood urea nitrogen (BUN) and creatinine levels; another patient had chronic renal insufficiency in a nonirradiated kidney.
  • One patient developed diffuse interstitial pneumonitis.
  • Four patients developed benign neoplasms; three were in the RT field (two osteochondroma, one lipoma) and one outside (cervical intraepithelial neoplasia II).
  • There were three second malignancies (chronic myelogenous leukemia at 9 years, osteosarcoma at 11 years, and breast cancer at 25 years after initial diagnosis of nephroblastoma); both solid malignancies occurred in the RT field.
  • CONCLUSIONS: Late effects of therapy were seen in more than two thirds of children treated for Wilms' tumor.
  • [MeSH-minor] Child. Child, Preschool. Dose-Response Relationship, Radiation. Female. Fertility / radiation effects. Follow-Up Studies. Humans. Infant. Intestinal Obstruction / etiology. Intestine, Small / radiation effects. Kidney Diseases / etiology. Kyphosis / etiology. Male. Muscles / radiation effects. Neoplasm Staging. Neoplasms, Second Primary / etiology. Puberty, Delayed / etiology. Scoliosis / etiology. Time Factors

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  • (PMID = 10725637.001).
  • [ISSN] 0360-3016
  • [Journal-full-title] International journal of radiation oncology, biology, physics
  • [ISO-abbreviation] Int. J. Radiat. Oncol. Biol. Phys.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] UNITED STATES
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19. Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY: Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res; 2001 Jul-Aug;21(4B):2895-900
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  • 1) recently resected urinary bladder cancer;.
  • 3) uterine cervical intraepithelial neoplasm (CIN);.
  • If no toxicity > or = grade II was noted in at least 3 successive patients, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day.
  • There was no treatment-related toxicity up to 8,000 mg/day.
  • Beyond 8,000 mg/day, the bulky volume of the drug was unacceptable to the patients.
  • One of 4 patients with CIN and 1 of 7 patients with oral leucoplakia proceeded to develop frank malignancies in spite of curcumin treatment.
  • In contrast, histologic improvement of precancerous lesions was seen in 1 out of 2 patients with recently resected bladder cancer, 2 out of 7 patients of oral leucoplakia, 1 out of 6 patients of intestinal metaplasia of the stomach, I out of 4 patients with CIN and 2 out of 6 patients with Bowen's disease.
  • Our results also suggest a biologic effect of curcumin in the chemoprevention of cancer.
  • [MeSH-major] Anticarcinogenic Agents / therapeutic use. Bowen's Disease / drug therapy. Carcinoma, Transitional Cell / drug therapy. Cervical Intraepithelial Neoplasia / drug therapy. Curcumin / therapeutic use. Leukoplakia, Oral / drug therapy. Precancerous Conditions / drug therapy. Skin Neoplasms / drug therapy. Stomach / pathology. Stomach Neoplasms / prevention & control. Urinary Bladder Neoplasms / drug therapy. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Aged. Arsenicals / adverse effects. Dose-Response Relationship, Drug. Female. Humans. Male. Metaplasia. Middle Aged. Neoplasm Recurrence, Local / prevention & control. Prospective Studies. Risk. Treatment Outcome


20. Soergel P, Wang X, Stepp H, Hertel H, Hillemanns P: Photodynamic therapy of cervical intraepithelial neoplasia with hexaminolevulinate. Lasers Surg Med; 2008 Nov;40(9):611-5
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  • [Title] Photodynamic therapy of cervical intraepithelial neoplasia with hexaminolevulinate.
  • BACKGROUND AND OBJECTIVE: CIN is a disease of women in their reproductive years, and treatment includes excisional techniques with increased risk of preterm deliveries.
  • Photodynamic therapy (PDT) using topical precursor of photoactive porphyrins may be a non-invasive alternative with minimal side effects.
  • This study assessed the feasibility and response rate of PDT with hexaminolevulinate (HAL) in cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection.
  • STUDY DESIGN/MATERIALS AND METHODS: Twenty four patients with a CIN 2 or 3 or a persistent CIN 1 and a positive high-risk HPV-DNA test were included.
  • Each patient had gynaecologic examination including cervical cytology, HPV DNA testing, colposcopy and biopsy.
  • Ten milliliters of HAL-thermogel (10 mM) were topically applied to the cervix for 3-5 hours, followed by 1,000 seconds of illumination of both ecto- and endocervical canal with red coherent light (wave length 633 nm) using a PDT laser and a special light catheter.
  • RESULTS: Seven, 10, and 7 patients had a CIN 1, 2, or 3, respectively.
  • Treatment could be accomplished in all cases and no severe side effects were encountered.
  • Fifteen out of the 24 patients had a complete response (15/24 = 63%) and a HPV remission 6 months after 1-3 treatments.
  • The remission rates were 71%, 50%, and 71% for CIN 1, 2 and 3.
  • CONCLUSION: HAL PDT seems to be a non-invasive, repeatable procedure for CIN and cervical HPV infection with minimal side effects which can be easily performed on outpatient basis.
  • [MeSH-major] Aminolevulinic Acid / analogs & derivatives. Cervical Intraepithelial Neoplasia / drug therapy. Photochemotherapy. Photosensitizing Agents / therapeutic use. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Feasibility Studies. Female. Humans. Papillomavirus Infections / drug therapy. Papillomavirus Infections / pathology. Treatment Outcome. Young Adult


21. Kiatpongsan S, Niruthisard S, Mutirangura A, Trivijitsilp P, Vasuratna A, Chaithongwongwatthana S, Lertkhachonsuk R: Role of human papillomavirus DNA testing in management of women with atypical squamous cells of undetermined significance. Int J Gynecol Cancer; 2006 Jan-Feb;16(1):262-5
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  • [Title] Role of human papillomavirus DNA testing in management of women with atypical squamous cells of undetermined significance.
  • To find the sensitivity, specificity, and positive and negative predictive values of the high-risk group human papillomavirus (HPV) DNA testing as a triage tool to detect high-grade squamous intraepithelial lesions (HSILs, ie, cervical intraepithelial neoplasia [CIN] 2 or worse) in women with a cytologic smear showing atypical squamous cells of undetermined significance (ASC-US).
  • Cervical cell samplings were done by cervical cytobrush technique and tested for high-risk group HPV with the Hybrid Capture 2 (HC2) test.
  • Then cervicographs were taken before colposcopic-directed cervical biopsies were done.
  • Of the 90 ASC-US cases enrolled, the pathologic results were normal in 30.0%, squamous metaplasia in 16.7%, CIN 1 in 37.8%, CIN 2 in 1.1%, CIN 3 in 11.1%, and microinvasive cervical carcinoma in 3.3%.
  • The prevalence of HSILs and the prevalence of high-risk HPV detection were 15.6% and 38.9%, respectively.
  • Using pathologic results from cervical biopsy as the gold standard, the HC2 has the sensitivity, specificity, and positive and negative predictive values of 85.7%, 69.7%, 34.3%, and 96.4%, respectively, to detect HSILs.
  • High-risk group HPV detection can be used as an additional triage test to detect HSILs in women having ASC-US with high sensitivity and negative predictive value.
  • [MeSH-major] Carcinoma, Squamous Cell / virology. Cervical Intraepithelial Neoplasia / virology. DNA, Viral / analysis. Papillomaviridae / isolation & purification. Uterine Cervical Neoplasms / virology
  • [MeSH-minor] Adolescent. Adult. Biopsy, Needle. Cohort Studies. DNA Probes, HPV. Female. Humans. Immunohistochemistry. Middle Aged. Papillomavirus Infections / diagnosis. Papillomavirus Infections / drug therapy. Risk Assessment. Sensitivity and Specificity. Thailand. Triage

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  • (PMID = 16445642.001).
  • [ISSN] 1048-891X
  • [Journal-full-title] International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
  • [ISO-abbreviation] Int. J. Gynecol. Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / DNA Probes, HPV; 0 / DNA, Viral
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22. Luxton JC, Nath R, Derias N, Herbert A, Shepherd PS: Human papillomavirus type 16-specific T cell responses and their association with recurrence of cervical disease following treatment. J Gen Virol; 2003 May;84(Pt 5):1063-70
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Human papillomavirus type 16-specific T cell responses and their association with recurrence of cervical disease following treatment.
  • Human papillomavirus type 16 (HPV-16) L1- and E7-specific T cell responses were measured in 58 women with abnormal cervical cytology in a prospective study.
  • On recruitment, patients responded most frequently and with the highest numbers of responding cells to the L1 region aa 311-345 and this response was significantly associated with the presence of cervical disease (P=0.041).
  • Responses to the L1 peptide aa 281-295 were significantly higher in patients with CIN III than in those with HPV/CIN I or CIN II lesions (P=0.027).
  • The E7 region aa 70-98 was the most immunogenic in patients with squamous intraepithelial lesions of the cervix (SIL) but the responses detected were not significantly higher than in patients without SIL.
  • Following treatment, the T cell response profiles of patient groups did not change significantly.
  • Recurrence of disease was associated with T cell responses to the E7 region aa 70-98 at the patient's first clinic visit (P=0.017).
  • [MeSH-major] Capsid Proteins. Cervical Intraepithelial Neoplasia / physiopathology. Papillomaviridae / immunology. T-Lymphocytes / immunology. Uterine Cervical Diseases / drug therapy. Uterine Cervical Diseases / physiopathology. Uterine Cervical Neoplasms / physiopathology

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  • (PMID = 12692269.001).
  • [ISSN] 0022-1317
  • [Journal-full-title] The Journal of general virology
  • [ISO-abbreviation] J. Gen. Virol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Capsid Proteins; 0 / L1 protein, Human papillomavirus type 16; 0 / Oncogene Proteins, Viral; 0 / Papillomavirus E7 Proteins; 0 / Peptides; 0 / oncogene protein E7, Human papillomavirus type 16
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23. Del Priore G, Gudipudi DK, Montemarano N, Restivo AM, Malanowska-Stega J, Arslan AA: Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecol Oncol; 2010 Mar;116(3):464-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia.
  • OBJECTIVE: Standard surgical treatment for CIN may impair fertility generating a need for alternative treatment options.
  • We tested the efficacy and toxicity of oral DIM in the treatment of CIN 2 or 3 lesions.
  • METHODS: Patients with biopsy-proven cervical intraepithelial neoplasia (CIN) 2 or 3 scheduled for loop electrosurgical excision procedure (LEEP) were randomized 2:1 to receive diindolylmethane (DIM) (BioResponse-DIM, BioResponse, Boulder, CO) orally at approximately 2 mg/kg/day for 12 weeks or placebo (defatted rice bran, BioResponse).
  • At enrollment, 58% were diagnosed with CIN 2 and 42% with CIN 3, 57% of subjects were Caucasian, 15% African American, 12% Hispanic and 17% Asian.
  • During treatment 2 subjects (3%) complained of nausea (grade 2) at the 3- to 4-month visit.
  • Twenty-one subjects (47%) in the DIM group had improved CIN with a decrease by 1-2 grades or a normal result.
  • Median time to improvement was 5 months.
  • Stratifying by level of dysplasia, age, race, HPV status, tobacco use, contraceptive used did not alter the results.
  • We observed a high rate of clinically significant improvement in confirmed CIN 2 or 3 lesions among both treatment groups in this randomized clinical trial.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / drug therapy. Indoles / administration & dosage. Uterine Cervical Neoplasms / drug therapy


24. Istomin YP, Lapzevich TP, Chalau VN, Shliakhtsin SV, Trukhachova TV: Photodynamic therapy of cervical intraepithelial neoplasia grades II and III with Photolon. Photodiagnosis Photodyn Ther; 2010 Sep;7(3):144-51
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Photodynamic therapy of cervical intraepithelial neoplasia grades II and III with Photolon.
  • The objective of the present study was to test in clinics a previously developed novel organ-saving approach for the treatment of CIN using PDT with the photosensitizer Photolon applied in women of a childbearing age with CIN II and III.
  • A total number of 112 patients aged 35.2+/-1.6 with morphologically proven diagnosis of CIN II and III were enrolled into the study.
  • In 3 months after treatment a complete eradication of the HPV infection was proven by PCR-analysis in 47 (53.4%) from 88 patients who have been infected with HPV of a highly oncogenic strains before PDT.
  • PDT with Photolon is an alternative approach for the treatment of cervical intraepithelial neoplasia which can be recommended for women of childbearing age.
  • The simplicity of the procedure as well as its' high therapeutic efficacy defines the reasonability of its' introduction into the clinical practice as a new organ-saving method for the treatment of patients with cervical intraepithelial neoplasia.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / drug therapy. Photochemotherapy / methods. Photosensitizing Agents / therapeutic use. Povidone / therapeutic use. Protoporphyrins / therapeutic use. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Female. Humans. Neoplasm Staging. Papillomavirus Infections / complications. Papillomavirus Infections / drug therapy


25. Ichimura H, Yamaguchi S, Kojima A, Tanaka T, Niiya K, Takemori M, Hasegawa K, Nishimura R: Eradication and reinfection of human papillomavirus after photodynamic therapy for cervical intraepithelial neoplasia. Int J Clin Oncol; 2003 Oct;8(5):322-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Eradication and reinfection of human papillomavirus after photodynamic therapy for cervical intraepithelial neoplasia.
  • BACKGROUND: Photodynamic therapy (PDT) has been proven to be a promising therapeutic modality for selected dysplasias and malignancies in a variety of organs.
  • We assessed the effectiveness of PDT for treating cervical intraepithelial neoplasia (CIN) by cytological and histological examinations and investigated its impact on human papillomavirus (HPV) infection.
  • METHODS: A series of 31 patients with CIN (2 with CIN2, 29 with CIN3) were given polyhematoporphyrin ether/ester (PHE) 2 mg/kg IV.
  • HPV-DNA extracted from cervical smears was amplified by the polymerase chain reaction and typed for HPV using restriction fragment length polymorphism.
  • RESULTS: At 3 months after PDT, cytology and directed biopsy of the cervix revealed regression of the disease in 28 [complete remission (CR) rate 90%] of 31 patients, and HPV-DNA could be no longer detected in the cervical smears of 22 (76%) of 29 HPV-positive patients.
  • After 12 months, all 31 patients had achieved a CR on biopsy, although HPV-DNA was still present in the cervical smears of 6 patients.
  • The types of HPV-DNA detected 12 months after PDT were different from those seen before PDT in each of the 6 patients, suggesting that they might be reinfected with other HPV types after PDT.
  • CONCLUSION: PDT is effective not only in improving the cytological and histological measures when treating CIN but also for eradicating cervical HPV.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / drug therapy. Cervical Intraepithelial Neoplasia / virology. Papillomaviridae / isolation & purification. Photochemotherapy. Uterine Cervical Neoplasms / drug therapy. Uterine Cervical Neoplasms / virology
  • [MeSH-minor] Adult. Antineoplastic Agents / therapeutic use. Antiviral Agents / therapeutic use. Cervix Uteri / virology. DNA, Viral / analysis. Dihematoporphyrin Ether / therapeutic use. Female. Humans. Papillomavirus Infections / drug therapy. Recurrence

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  • (PMID = 14586759.001).
  • [ISSN] 1341-9625
  • [Journal-full-title] International journal of clinical oncology
  • [ISO-abbreviation] Int. J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Antiviral Agents; 0 / DNA, Viral; 97067-70-4 / Dihematoporphyrin Ether
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26. Piura B, Rabinovich A, Huleihel M: [Matrix metalloproteinases and their tissue inhibitors in malignancies of the female genital tract]. Harefuah; 2003 Nov;142(11):786-91, 804

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Matrix metalloproteinases and their tissue inhibitors in malignancies of the female genital tract].
  • Their proteolytic activity depends on their binding to metal Zinc and is controlled by tissue inhibitors of MMP (TIMPs).
  • Since MMPs may serve as markers of tumor behavior and as predictors of survival and since synthetic inhibitors of MMP may have a place in the treatment of cancer, researching MMPs and their tissue inhibitors in malignant diseases has attracted growing attention.
  • Studies on MMPs and their tissue inhibitors in malignancies of the female genital tract have shown the following:.
  • 1) In ovarian carcinoma and cervical carcinoma, over-expression of MMP-2 and MMP-9 is associated with invasiveness, metastatic spread and poor prognosis;.
  • 3) In cervical intra-epithelial neoplasia (CIN), measuring MMP-2 can assist in identifying high-risk for progression CIN I and CIN II; 4).
  • In vulvar squamous cell carcinoma, over-expression of MMP-13 is associated with invasiveness, metastatic spread and poor prognosis.
  • It is speculated that using synthetic drugs that inhibit MMPs in combination with conventional chemotherapy may contribute to the improvement of treatment results in cancer patients.
  • [MeSH-major] Genital Neoplasms, Female / enzymology. Genital Neoplasms, Female / pathology. Matrix Metalloproteinases / metabolism. Tissue Inhibitor of Metalloproteinases / metabolism

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  • (PMID = 14631913.001).
  • [ISSN] 0017-7768
  • [Journal-full-title] Harefuah
  • [ISO-abbreviation] Harefuah
  • [Language] heb
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Israel
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Tissue Inhibitor of Metalloproteinases; EC 3.4.24.- / Matrix Metalloproteinases
  • [Number-of-references] 32
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27. Snoeck R, Andrei G, De Clercq E: Cidofovir in the treatment of HPV-associated lesions. Verh K Acad Geneeskd Belg; 2001;63(2):93-120, discussion 120-2
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Cidofovir in the treatment of HPV-associated lesions.
  • The acyclic nucleoside phosphonate cidofovir (CDV) has proved efficacious in the treatment of different clinical manifestations of HPV-induced epithelial cell proliferation.
  • Local intratumor injections of CDV in an immunocompetent patient with hypopharyngeal/esophageal papillomatous lesions, PCR-positive for HPV types 16 and 18, resulted in a complete regression of the tumor.
  • In addition, CDV topical gel has been successfully used for the treatment of severe, relapsing anogenital HPV lesions and cervical intraepithelial neoplasia (CIN) grade III.
  • In vitro, treatment of HPV-positive cells (compared to normal primary human keratinocytes) with CDV has resulted in a concentration- and time-dependent inhibition of cell proliferation.
  • Different parameters of apoptosis, i.e., (i) induction of CPP32 (caspase-3) protease activity, (ii) translocation of phosphatidylserine (PS) from the inner part of the plasma membrane to the outer layer, (iii) disintegration of the nuclear matrix protein (NMP), (iv) DNA fragmentation, (v) number of cells in apoptotic phase following cell cycle analysis, showed that the mechanism of cell death following treatment with CDV is based on apoptosis.
  • In conclusion, CDV has great potential in the treatment of severe HPV-induced proliferative lesions, either laryngeal, esophageal/pharyngeal or genital.
  • As CDV has proved able to induce apoptosis, in a time- and concentration-dependent manner, in a number of HPV-positive cell lines, the regression of papillomatous tumors observed with CDV in patients, may be due, at least in part, to the induction of apoptosis.
  • [MeSH-major] Antiviral Agents / therapeutic use. Cytosine / therapeutic use. Organophosphonates. Organophosphorus Compounds / therapeutic use. Papillomaviridae. Papillomavirus Infections / drug therapy. Tumor Virus Infections / drug therapy
  • [MeSH-minor] Administration, Topical. Apoptosis / drug effects. Cell Division / drug effects. Female. Humans. Injections, Intravenous. Male

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  • (PMID = 11436421.001).
  • [ISSN] 0302-6469
  • [Journal-full-title] Verhandelingen - Koninklijke Academie voor Geneeskunde van BelgieĢˆ
  • [ISO-abbreviation] Verh. K. Acad. Geneeskd. Belg.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Belgium
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / Organophosphonates; 0 / Organophosphorus Compounds; 8J337D1HZY / Cytosine; JIL713Q00N / cidofovir
  • [Number-of-references] 57
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