Efficacy in treatment of subclinical cervical HPV infection without intraepithelial neoplasia
systematic review
Keywords:
HPV, Cervical Intraepithelial Neoplasia, Treatment, Systematic ReviewAbstract
CONTEXT: The treatment of the subclinical Human papillomavirus (HPV) infection of the uterine cervix is controversial. OBJECTIVE: To assess the efficacy of any therapy for subclinical HPV infection of the cervix without intraepithelial neoplasia, via a search in the medical literature. METHOD: We performed a systematic review with a comprehensive reference search in Medline, LILACS, Excerpta Medica, AIDSLINE, Popline, Cochrane Library and other authors' reference lists to identify experimental studies of therapy for subclinical HPV infection without intraepithelial neoplasia of the uterine cervix. In order to identify unpublished studies, we also contacted experts in the area, clinical trial registries, pharmaceutical industries, government and research institutions. We also searched on the Internet and in the book-of-abstracts of some medical conferences. The studies identified were masked and selected by inclusion criteria to help ascertain their internal validity. The data about regression or progression of HPV infection were extracted from the studies included. RESULTS: We identified 67 studies related to the treatment of subclinical HPV infection without intraepithelial neoplasia of the uterine cervix. Only five clinical trials matched the inclusion criteria and none demonstrated significant differences between the experimental group and the control group concerning regression of HPV infection (with or without CIN I) or progression to higher grades of CIN. CONCLUSION: The evidence we found in the medical literature regarding the efficacy of any therapy for subclinical HPV infection without intraepithelial neoplasia of the uterine cervix was unsatisfactory.
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Reid R, Stanhope CR, Herschman BR, Booth E, Phibbs GD, Smith JP. Genital warts and cervical cancer: I. Evidence of an association between subclinical papillomavirus infection and cervical malignancy. Cancer 1982;50:377-87.
Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? JAMA 1993;270(21):2598-601.
Petitti DB. Meta-analysis, Decision analysis and cost-effectiveness analysis - methods for quantitative synthesis in medicine. Oxford: Oxford University Press 1994.
Guyatt GH, Rennie D. Users' guides to the medical literature [editorial]. JAMA 1993;270(17):2096-7.
Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Measur 1960;20:37-46.
Bartko JJ, Carpenter WT. On the methods and theory of reliability. J Nerv Ment Dis 1976;163(5):307-17.
Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33:159-74.
Dunn G, Everitt B. Clinical biostatistics: an introduction to evidence-based medicine. New York: John Wiley & Sons; 1995.
Gori J, Castano R, Dominguez J, et al. Laser vaporization, cryotherapy and trichloroacetic acid application in the therapy of ectocervical condylomatous lesions: a comparison of clinical results. Cervix 1992;10(4):217-9.
Madej J, Basta A, Madej Jr JG, Strama M. Colposcopy staging and treatment of papillomavirus infection of the cervix. Clin Exp Obstet Gynecol 1992;19(1):34-9.
Minucci D, Cinel A, Insacco E. Diathermic loop treatment for CIN and HPV lesions. A follow-up of 130 cases. Eur J Gynecol Oncol 1991;12(5):385-93.
Naud P, Monego H, Ricco L, Catalan F. O uso de nitrogęnio líquido na terapęutica do papilomavirus humano (HPV) com confirmaçăo por hibridizaçăo molecular. XV Brazilian Congress of Gynecology and Obstetrics; 1989 (Book of Abstracts).
Pietroluongo A, Pereira Filho A, Levente A. Tratamento das viroses pelo papilomavirus humano (HPV) com vacina BCG. XV Brazilian Congress of Gynecology and Obstetrics; 1989 (Book of Abstracts).
Salvo A, Rojas I, Figueiroa L, Stuardo P. Imunoterapia por via cutanea con dinitroclorobenceno en infeccion del cuello uterino por virus papiloma. Rev Child Obstet Ginecol 1991;56(6):460-3.
Torrisi A, Cinel A, Wittemberg L, Minucci D. Therapy with ß-interferon cream in the cervical-vaginal infections by Human papilloma virus (HPV). Eur J Gynecol Oncol 1987;7(4-5):441.
Trofatter Jr. Interferon treatment of anogenital papillomavirus-related diseases. Dermatol Clin 1991;9(2):343-52.
Yliskoski M, Syrjänen K, Syrjänen S, Saarikoski S, Nethersell A. Systemic alpha-interferon (Wellferon) treatment of genital Human papillomavirus (HPV) Type 6,11,16 and 18 infections: a double-blind, placebo-controlled trial. Gynecol Oncol 1991;43:55-60.
Woodman CBJ, Byrne P, Kelly KA, Hilton C. A randomized trial of laser vaporization in the management of cervical intraepithelial neoplasia associated with Human papillomavirus infection. J Public Health Med 1993;15(4):327-31.
Boothby RA, Carlson JA, Rubin M, Morgan M, Mikuta JJ. Single application treatment of human papillomavirus infection of the cervix and vagina with trichloroacetic acid: a randomized trial. Obstet Gynecol 1990;76(2):278-80.
Diakomanolis E, Rodolakis A, Simiakaki H, Frangopoulou E, Efstratiadou M. Randomized control trial of laser vaporization in the management of Human papillomavirus infection in the uterine cervix. Rec Adv Cerv Pathol Colposc, 1990;3:505-10.
Ruge S, Felding C, Skouby SO, Lundvall F, Hording U, Norrild B. CO2 laser vaporization in the treatment of cervical Human papillomavirus infection in women with abnormal Papanicolaou smears. Gynecol Obstet Invest 1992;33(3):172-6.
Hording U, Rygaard C, Ruge S, Felding C, Lundvall F, Junge J. Cervical koilocytosis and high risk HPV types: the benefit of laser vaporization. Eur J Obstet Gynecol Reprod Biol 1993;51(2):125-30.
Fairley CK, Tabrizi SN, Chen S, et al. A randomized trial of beta-carotene vs. placebo for the treatment of cervical HPV infection. Int J Gynecol Cancer 1996;6:225-30.
Ali SW, Evans AS, Monaghan JM. Results of CO2 laser cylinder vaporization of cervical intraepithelial disease in 1234 patients. An analysis of failures. Br J Obstet Gynecol 1986:93(1):75-8.
Baggish MS. Treating viral venereal infection with the CO2 laser. J Reprod Med 1982;27(12):737-42.
Benrubi G, Nuss RC, Holmes K, Lammert N. Efficacy of cryotherapy in the treatment of human papillomavirus infection of the uterine cervix. J Fla Med Assoc 1986;73(3):188-91.
Benrubi GI, Shannon J, Glazer J, Nuss RC. Cervical human papilloma virus infection: is treatment possible? J Fla Med Assoc 1988;75(12):799-800.
Boothby RA, Benrubi GI, Nuss RC, Lammert N. Laser treatment of Human papillomavirus infections of the uterine cervix. Colposc Gynecol Laser Surg 1986;2(1):25-9.
Brodman M, Dottino P, Friedman Jr F, Heller D, Bleiweiss I, Sperling R Human papillomavirus-associated lesions of the vagina and cervix. Treatment with a laser and issueal 5-fluorouracil. J Reprod Med 1992;37(5):453-6.
Caballero F, Baez J, Troya CI. La crioterapia en el tratamiento de las lesiones premalignas del cervix uterino. Rev Med Caja Seguro Social 1985;17(2):140-3.
Cinel A, Wittenberg L, Minucci D. ß-interferon issueal treatment in low and high-risk cervical lesions. Clin Exp Obstet Gynecol 1991;18(2):91-7.
Costa S, Poggi MG, Palmisano L, Syrjänen S, Yliskoski M, Syrjänen K. Intramuscular ß-interferon treatment of Human papillomavirus lesions in the lower female genital tract. Cervix 1988;6:203-12.
das Dores GB, Martins NV, Focchi J, et al. Tratamento da infecçăo cérvico-vaginal por papilomavirus humano HPV com quatro fármacos. J Bras Ginecol 1993;103(6):205-10.
das Dores GB, Ribalta JCL, Martins NV, et al Tratamento da infecçăo do colo uterino por papilomavirus humano com interferon gel. Rev Paul Med 1991;109(4):179-83.
Davila GW, Shroyer KR. Issueal 5-fluorouracil in the treatment of cervical Human papillomavirus infection. Gynecol Obstet Invest 1996;41(4):275-7.
Diakomanolis E, Rodolakis A, Dailianas S, Kalpaktsogiou K, Sakellaropoulos G, Aravantinos D. Long term results of CO2 laser treatment of low-grade squamous intraepithelial lesions. Cervix 1995;13:149-52.
Evans AS, Monaghan JM, Beattie AB. Carbon dioxide laser treatment of cervical warty atypias. Gynecol Oncol 1984;17:296.
Gal D, Friedman M, Mitrani-Rosenbaum S. Transmissibility and treatment failures of different types of human papillomavirus. Obstet Gynecol 1989;73(3 Pt 1):308-11.
Gall SA, Constantine L, Koukol D. Therapy of persistent human papillomavirus disease with two different interferon species. Am J Obstet Gynecol 1991;164(1):130-4.
Gonzalez-Sanchez JL, Celis C, Rodriguez-de-Santiago JD, Pena-Sandoval M, Menendez-Velasquez J. Tratamiento del virus del papiloma humano (VPH) del cervix con criocirugia. Ginecol Obstet Mex 1991;59:164-8.
Husseinzadeh N, Guoth JG, Jayawardena DS. Subclinical cervicovaginal human papillomavirus infections associated with cervical condylomata and dysplasia. Treatment outcomes. J Reprod Med 1994;39(10):777-80.
Klutke JJ, Bergman A. Interferon as an adjuvant treatment for genital condyloma acuminatum. Int J Gynecol Obstet 1995;49:171-4.
Lira Neto JB, Santos JF, Vieira IM. Infecçăo ginecológica pelo vírus do condiloma. Contribuiçăo ao diagnóstico e terapęutica. J Bras Ginecol 1984;94:295.
Luesley MD, Cullimore J, Redman CWE, et al. Loop diathermy excision of the cervical transformation zone in patients with abnormal cervical smears. BMJ 1990;300:1690-3.
Maldonado P, Christo Jr WG, Mannarino MPB. Ensaio terapęutico com Thuya occidentalis em pacientes portadoras de infecçăo pelo HPV no trato genital inferior. Annals of the IX Brazilian Congress of Cervical Pathology and Colposcopy; 1992.
Maldonado P, Christo WG, Costa CM, Pollastri CE, Cavalcanti RMVF, Pereira NA. Conduta nas infecçőes cervicovaginais pelo HPV no IG UFRJ. Femina 1991;19:324.
Malviya VK, Deppe G, Pluszczynski R, Boike G. Trichloroacetic acid in the treatment of human papillomavirus infection of the cervix without associated dysplasia. Obstet Gynecol 1987;70:72-4.
Markowska J, Nowak M, Niecewicz R, Breborowicz J, Wiese E, Zengteler G. Results of issueal treatment of HPV infection in the uterine cervix using interferon beta, 13-cis-retinoic acid and TFX. Eur J Gynecol Oncol 1994;15(1):65-9.
Menendez-Velazquez JF, Gonzalez-Sanchez JL, Rodriguez-de-Santiago JD, Munoz-Reyes R, Bailon-Uriza R. Tratamiento de la infeccion cervical por el virus del papiloma humano (VPH) con acido tricloroacetico. Ginecol Obstet Mex 1993;61:48-51.
Merkur H, Baird PJ. Papillomavirus infection of the female genital tract before and after treatment: a cytological, colposcopic and histological study. Aust N Z J Obstet Gynecol 1989;29(3 Pt 1):185-8.
Milla-Villeda RH, Gurrola-Medrano T. Tratamiento de la infeccion cervical subclinica por el virus del papiloma humano (VPH) con asa diatermica. Eficacia a corto plazo. Ginecol Obstet Mex 1995;63:293-6.
Mitchell H, Medley G. Evidence against diathermy as a beneficial treatment for HPV infection of the cervix. Aust N Z J Obstet Gynecol 1989;29(4):439-42.
Mohanty KC, Lowe JW. Cryotherapy in the management of histologically diagnosed subclinical HPV infection of the cervix. Br J Clin Pract 1990;44(12):574-7.
Mohanty KC, Lowe JW. Cold coagulation therapy in the treatment of histologically diagnosed subclinical human papillomavirus infection of the cervix. Br J Clin Pract 1991;45(2):102-4.
Nieminen P, Aho M, Lehtinen M, Vesterinen E, Vaheri A, Paavonen J. Treatment of genital HPV infection with carbon dioxide laser and systemic interferon alpha-2b. Sex Transm Dis 1994;21(2):65-9.
Puttemans P, van Pelle Y, De Muylder E. Carbon dioxide laser vaporization of cervical subclinical papillomaviral infection neoplasia: short-term effectiveness. Eur J Obstet Gynecol Reprod Biol 1986;23:167-80.
Qian ZW, Mao SJ, Cai XC, et al. Viral etiology of chronic cervicitis and its therapeutic response to a recombinant interferon. Chin Med J 1990;103(8): 647-51.
Riva JM, Sedlacek TV, Cunnane MF, Mangan CE. Extended carbon dioxide laser vaporization in the treatment of subclinical papillomavirus infection of the lower genital tract. Obstet Gynecol 1989;73(1):25-30.
Rogstad KE, Dixon CA, Ahmed IH. The management of subclinical wart virus infection of the cervix in a genitourinary clinic. Geniturin Med 1992;68(5):307-8.
Ruge S, Felding C, Skouby SO, Lundvall F, Hording U. CO2 laser vaporization of human papillomavirus (HPV)-induced abnormal cervical smears. A simple and effective solution to a recurrent clinical problem. Clin Exp Obstet Gynecol 1991;18(2):99-101.
Schneider A, Papendick U, Gissmann L, De Villiers E-M. Interferon treatment of human genital papillomavirus infection: importance of viral type. Int J Cancer 1987;40:610-4.
Semprini AE, Stillo A, Marcozzi S, Castagna C, Fiore S, Radaelli U. Treatment with interferon for genital HPV in HIV-positive and HIV-negative women. Eur J Obstet Gynecol Reprod Biol 1994;53(2):135-7.
Sesti F, De-Santis L, Farne C, Mantenuto L, Piccione E. Efficacy of CO2 laser surgery in treating squamous intraepithelial lesions. An analysis of clinical and virologic results. J Reprod Med 1994;39(6):441-4.
Stefanon D. Activity of interferon-ß in small condylomatous lesions of the uterine cervix. Cervix 1983;1:23-6.
Stentella P, Frega A, Di-Renzi F, Palazzetti PL, Pachi A. Issue and systemic administration of natural alpha interferon in the treatment of female and male HPV genital infections. Clin Exp Obstet Gynecol 1996;23(1):29.
Strand A, Wilander E, Zehbe I, Rylander E. High risk HPV persists after treatment of genital papillomavirus infection but not after treatment of cervical intraepithelial neoplasia. Acta Obstet Gynecol Scand 1997;76(2):140.
Surwit EA, Grahan V, Droegemueller W, et al. Evaluation of issueally applied trans-retinoic acid in the treatment of cervical intraepithelial lesions. Am J Obstet Gynecol 1982;143(7):821-3.
Villani C, Nobili F, Stentella P, Pace S. The viral lesion (HPV) of the lower genital tract in teenagers: clinical and therapeutic aspects. Eur J Gynecol Oncol 1989;10(4):267-71.
Villani C, Vecchione A, Pace S, Carenza L. The rationale for treatment of cervical lesions (HPV +/- CIN). Clin Exp Obstet Gynecol 1989;16(1):44-7.
Ward BG, Thomas IL. Randomized prospective intervention study of Human cervical wart virus infection. Aust N Z J Obstet Gynecol 1994;34(2):182-5.
Weck PK, Buddin DA, Whisnant JK. Interferon in the treatment of genital Human papillomavirus infections. Am J Med 1988;85(Suppl 2A):159-64.
Winceslaus SJ, Brown C, Goh BT. Managing women with human papillomavirus changes in cervical cytology. Genitourin Med 1988;64(4):259-62.
Yliskoski M, Saarikoski S, Syrjänen K, Syrjänen S, Castrén O. Cryotherapy and CO2 laser vaporization in the treatment of cervical and vaginal HPV infections. Acta Obstet Gynecol Scand 1989;68(7):619-25.
Zarcone R. Treatment of genital HPV-infections with natural alpha interferon from normal human leukocytes. Clin Exp Obstet Gynecol 1995;22(1):14-9.
Zarcone R, Bellini P, Cardone G, Cardone A. Treatment of cervix condylomata with alpha-IFN leucocytar. Clin Exp Obstet Gynecol 1995;22(4):326-9.
Bosch FX, Manos MM, Munoz N et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. J Natl Cancer Inst, 1995;87:796-802.
Villa LL. Human papillomaviruses and cervical cancer. Adv Cancer Res, 1997;71:321-41.
