Advertisement
Research Article| Volume 20, ISSUE 2, P407-422, June 2000

Download started.

Ok

Treatment of Human Papillomavirus Gynecologic Infections

  • Karen J. Auborn
    Correspondence
    Address reprint requests to: Karen J. Auborn, PhD, HPV Laboratory, Boas-Mark Biomedical Science Research Center, 350 Community Drive, Manhasset, NY 11030
    Affiliations
    From the Department of Otolaryngology, Division of Research, Long Island Jewish Medical Center, New Hyde Park, New York

    The Long Island Campus of Albert Einstein College of Medicine, New Hyde Park, New York
    Search for articles by this author
  • Timothy H. Carter
    Affiliations
    Department of Biological Sciences, St. John’s University, Jamaica, New York
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.
      HPV causes a continuum of pathologies ranging from subclinical infection to visible condylomas and is even a cofactor for cervical cancer and other cancers of the female genital tract. Routine gynecologic examination and the advent of simple screening procedures for cervical dysplasia and cancer have decreased the impact of HPV disease among many women; however, cervical cancer remains a serious health problem in less economically developed regions, and genital warts are one of the most widespread STDs among all women. Furthermore, current treatments fail to eliminate the underlying viral infection, leading to the possibility of recurrent disease. We review the biology and epidemiology of HPV, discuss current treatment modalities, and summarize research on promising new avenues of prevention and therapy.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Alvarez-Salas L.M.
        • Cullinan A.E.
        • Siwkowski A.
        • et al.
        Inhibition of HPV-16 E6/E7 immortalization of normal keratinocytes by hairpin ribozymes.
        Proc Natl Acad Sei U S A. 1998; 95: 1189
        • Apgar B.S.
        Changes in strategies for human papillomavirus genital disease.
        Am Fam Physician. 1997; 55: 1545
        • Arany I.
        • Evans T.
        • Tyring S.K.
        Tissue specific HPV expression and down regulation of local immune responses in condylomas from HIV seropositive individuals.
        Sex Transm Infect. 1998; 74: 349
        • Arany I.
        • Rady P.
        • Tyring S.K.
        • et al.
        Interferon treatment enhances the expression of underphosphorylated (biologically active) retinoblastoma protein in human papilloma virus-infected cells through the inhibitory TGF beta 1/IFN beta cytokine pathway.
        Antiviral Res. 1994; 23: 131
        • Arany I.
        • Tyring S.K.
        Activation of local cell-mediated immunity in interferon-responsive patients with human papillomavirus-associated lesions.
        J Interferon Cytokine Res. 1996; 16: 453
        • Arany I.
        • Yen A.
        • Tyring S.K.
        p53, WAF1 / CIP1 and mdm2 expression in skin lesions associated with human papillomavirus and human immunodeficiency virus.
        Anticancer Res. 1997; 17: 1281
        • Arends M.J.
        • Donaldson Y.K.
        • Duvall E.
        • et al.
        Human papillomavirus type 18 associates with more advanced cervical neoplasia than human papillomavirus type 16.
        Hum Pathol. 1993; 24: 432
        • Auborn K.
        • Abramson A.
        • Bradlow H.L.
        • et al.
        Estrogen metabolism and laryngeal papillomatosis: A pilot study on dietary prevention.
        Anticancer Res. 1998; 18: 4569
        • Backe J.
        • Roos T.
        • Kaesemann H.
        • et al.
        Local therapy and adjuvant interferon therapy in genital papilloma virus infections.
        Gynakol Geburtshilfliche Rundsch. 1995; 35: 79
        • Baken L.A.
        • Koutsky L.A.
        • Kuypers J.
        • et al.
        Genital human papillomavirus infection among male and female sex partners; prevalence and type-specific concordance.
        J Infect Dis. 1995; 171: 429
        • Baker C.C.
        • Phelps W.C.
        • Lingren V.
        • et al.
        Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines.
        J Virol. 1987; 61: 962
        • Baker G.E.
        • Tyring S.K.
        Therapeutic approaches to papillomavirus infections.
        Dermatol Clin. 1997; 15: 331
        • Barnes W.
        • Woodworth C.
        • Waggoner S.
        • et al.
        Rapid dysplastic transformation of human genital cells by human papillomavirus type 18.
        Gynecol Oncol. 1990; 38: 343
        • Bauer H.M.
        • Ting Y.
        • Greer C.E.
        • et al.
        Genital human papilloma infection in female university students as determined by a PCR-based method.
        JAMA. 1991; 265: 472
        • Becker T.M.
        • Stone K.M.
        • Alexander E.R.
        Genital human papillomavirus infection: A growing concern.
        Obstet Gynecol Clin North Am. 1987; 14: 389
        • Beutner K.R.
        • Ferenczy A.
        Therapeutic approaches to genital warts.
        Am J Med. 1997; 102: 28
        • Boshart M.
        • Gissmann L.
        • Ikenberg H.
        • et al.
        A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer.
        EMBO J. 1984; 3: 1151
        • Charuruks N.
        • Voravud N.
        • Termrungruanglert W.
        • et al.
        13-cis-retinoic acid and interferon-alpha 2a therapy in locally advanced squamous cell carcinoma of the cervix: p53 alteration, proliferating cell nuclear antigen expression and angiogenesis response.
        J Obstet Gynacol Res. 1998; 24: 335
        • Chen Z.
        • Kamath P.
        • Zhang S.
        • et al.
        Effects on tumor cells of ribozymes that cleave the RNA transcripts of human papillomavirus type 18.
        Cancer Gene Ther. 1996; 3: 18
        • Clark P.R.
        • Roberts M.L.
        • Cowsert L.M.
        A novel drug screening assay for papillomavirus specific antiviral activity.
        Antiviral Res. 1998; 37: 97
        • Coll D.A.
        • Rosen C.A.
        • Auborn K.
        • et al.
        Treatment of recurrent respiratory papillomatosis with indole-3-carbinol.
        Am J Otolaryngol. 1997; 18: 283
        • Cover C.M.
        • Hsieh S.J.
        • Tran S.H.
        • et al.
        Indole-3-carbinol inhibits the expression of cyclindependent kinase-6 and induces G1 cell cycle arrest of human breast cancer cells independent of estrogen receptor signaling.
        J Biol Chem. 1998; 273: 3838
        • Daling J.R.
        • Sherman K.J.
        • Weiss N.S.
        Risk factors for condyloma acuminatum in women.
        Sex Transm Dis. 1986; 13: 16
        • DeVilliers E-M
        • Gissman L.
        • zur Hausen H.
        Molecular cloning of viral DNA from human genital warts.
        J Virol. 1981; 40: 932
        • Durst M.
        • Gissmann L.
        • Ikenberg H.
        • et al.
        A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions.
        Proc Natl Acad Sei U S A. 1983; 80: 3812
        • Dyson N.
        • Howley P.M.
        • Munger K.
        • et al.
        The human papilloma-virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product.
        Science. 1989; 243: 934
        • Facchini C.
        • Eremita G.A.
        • Bernabei A.
        Combination of beta-interferon and laser-C02 therapy in female HPV genitalis.
        Minerva Ginecol. 1996; 48: 345
        • Ge X.
        • Yannai S.
        • Rennert G.
        • et al.
        3,3’-Diindolylmethane induces apoptosis in human cancer cells.
        Biochem Biophys Res Commun. 1996; 228: 153
        • Giandomenico V.
        • Vaccari G.
        • Fiorucci G.
        • et al.
        Apoptosis and growth inhibition of squamous carcinoma cells treated with interferon-alpha, IFN-beta and retinoic acid are associated with induction of the cyclin-dependent kinase inhibitor p21.
        Eur Cytokine Netw. 1998; 9: 619
        • Gissmann L.
        • Schwarz E.
        Persistence and expression of human papillomavirus DNA in genital cancer.
        in: Everd D. Clark S. Papillomaviruses. John Wiley, Chichester1986: 190
        • Gissmann L.
        • Wolnik L.
        • Ikenberg H.
        • et al.
        Human papillomavirus type 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers.
        Proc Natl Acad Sei U S A. 1983; 80: 560
        • Gissmann L.
        • zurHausen H.
        Partial characterization of viral DNA from human genital warts (condylomata acuminata).
        Int J Cancer. 1980; 25: 605
        • Goodman M.T.
        • Kiviat N.
        • McDuffie K.
        • et al.
        The association of plasma micronutrients with the risk of cervical dysplasia in Hawaii.
        Cancer Epidemiol Biomarkers Prev. 1998; 7: 537
        • Gross G.
        Therapy of human papillomavirus infection and associated epithelial tumors.
        Intervirol. 1997; 40: 368
        • Gross G.
        • Von Krogh G.
        Therapy of anogenital HPV-induced lesions.
        Clin Dermatol. 1997; 15: 457
        • Hagensee M.E.
        Progress in the development of HPV vaccines.
        Infect Med. 1997; 14: 555
        • Hatch K.D.
        Clinical appearance and treatment strategies for human papillomavirus: A gynecologic perspective.
        Am J Obstet Gynecol. 1995; 172: 1340
        • He Y.
        • Huang L.
        Growth inhibition of human papillomavirus 16 DNA-positive mouse tumor by antisense RNA transcribed from U6 promoter.
        Cancer Res. 1997; 57: 3993
        • Ho G.Y.
        • Palan P.R.
        • Basu J.
        • et al.
        Viral characteristics of human papillomavirus infection and antioxidant levels as risk factors for cervical dysplasia.
        Int J Cancer. 1998; 78: 594
        • Horner M.
        Interferon in anogenital infections with human papillomavirus.
        Wien Med Wochenschr. 1993; 143: 464
        • Howett M.K.
        • Neely E.B.
        • Christensen N.D.
        • et al.
        A broad-spectrum microbicide with virucidal activity against sexually transmitted viruses.
        Antimicrob Agents Chemother. 1999; 43: 314
        • Ikeda M.
        • Noda K.
        • Hiura M.
        • et al.
        Late phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical cancer. ETP 21 Study Group—Cervical Cancer Group.
        Jpn J Cancer Chemother. 1998; 25: 2249
        • Jenson A.B.
        • Lancaster W.D.
        Association of human papillomavirus with benign, prema-lignant, and malignant anogenital lesions.
        in: Pfister H. Papillomaviruses and Human Cancer. CRC, Boca Raton1990: 11
        • Jin L.
        • Qi M.
        • Chen D-Z
        • et al.
        Indole-3-carbinol prevents cervical cancer in HPV16 transgenic mice.
        Cancer Res. 1999; 59: 1693
        • Johnson J.A.
        • Gangemi J.D.
        Selective inhibition of human papillomavirus-induced cell proliferation by (S)-l-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine.
        Antimicrob Agents Chemother. 1999; 43: 1198
        • Kavanagh J.J.
        • Verschraegen C.F.
        • Kudelka A.P.
        Irinotecan in cervical cancer.
        Oncology (Huntingt). 1998; 12: 94
        • Kelloff G.V.
        • Crowell J.A.
        • Hawk E.T.
        • et al.
        Strategy and planning for chemopreventative drug development plans II.
        J Cell Biochem. 1996; 26S: 54
        • Kenney J.W.
        Comparison of risk factors, severity, and treatment of women with genital HPV.
        Cancer Nurs. 1994; 17: 308
        • Keys H.M.
        • Bundy B.N.
        • Stehman F.B.
        • et al.
        Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma.
        N Engl J Med. 1999; 340: 1154
        • Klutke J.J.
        • Bergman A.
        Interferon as an adjuvant treatment for genital condyloma acuminatum.
        Int J Gynaecol Obstet. 1995; 49: 171
        • Kwasniewska A.
        • Charzewska J.
        • Tukendorf A.
        • et al.
        Dietary factors in women with dysplasia colli uteri associated with human papillomavirus infection.
        Nutr Cancer. 1998; 30: 39
        • Kwasniewska A.
        • Tukendorf A.
        • Semczuk M.
        Frequency of HPV infection and GSH levels in plasma of women with cervical dysplasia.
        Eur J Gynaecol Oncol. 1997; 18: 196
        • Lacey C.J.
        • Thompson H.S.
        • Monteiro E.F.
        • et al.
        Phase Ila. safety and immunogenicity of a therapeutic vaccine, लA-GW in persons with genital warts.
        J Infect Dis. 1999; 179: 612
        • Linnehan M.J.
        • Andrews S.
        • Groce N.E.
        College health providers’ knowledge, attitudes, and management practices of genital HPV infection.
        Nurse Pract. 1996; 21: 122
        • Liu H.
        • Wormke M.
        • Safe S.H.
        • et al.
        Indolo[3,2-b]carbazole: A dietary derived factor that exhibits both antiestrogenic and estrogenic activity.
        J Natl Cancer Inst. 1994; 86: 1758
        • Lorincz A.T.
        • Lancaster W.D.
        • Temple G.F.
        Cloning and characterization of a new type of human papilloma virus from a woman with dysplasia of the uterine cervix.
        J Virol. 1986; 58: 225
        • Lowy D.R.
        • Schiller J.T.
        Papillomaviruses: prophylactic vaccine prospects.
        Biochim Biophys Acta. 1999; 1423: M1
        • Lutzner V.A.
        • Blanchet-Bardon C.
        • Orth G.
        • et al.
        Clinical observations, virologic studies and treatment trials in patients with epidermodysplasia-verruciformis, a disease induced by specific human papillomaviruses.
        J Invest Dermatol. 1984; 198: 83s
        • Maehama T.
        • Patzelt A.
        • Lengert M.
        • et al.
        Selective down-regulation of human papillomavirus transcription by 2-deoxyglucose.
        Int J Cancer. 1998; 76: 639
        • Markowska J.
        • Nowak M.
        • Niecewicz R.
        • et al.
        Results of topical treatment of HPV infection in the uterine cervix using interferon beta, 13-cis-retinoic acid and TFX.
        Eur J Gynaecol Oncol. 1994; 15: 65
        • Miller D.M.
        • Brodell R.T.
        Human papillomavirus infection: Treatment options for warts.
        Am Fam Physician. 1996; 53: 135
        • Morris M.
        • Eifel P.J.
        • Lu J.
        • et al.
        Pelvic radiation with concurrent chemotherapy compared with pelvic and par-aortic radiation for high-risk cervical cancer.
        N Engl J Med. 1999; 340: 1137
        • Mounts P.
        • Shah K.V.
        Respiratory papillomatosis: Etiological relation to genital tract papillomaviruses.
        Prog Med Virol. 1984; 29: 90
        • Mundt A.J.
        • Rotmensch J.
        • Waggoner S.
        • et al.
        Phase I trial of concomitant chemoradiotherapy for cervical cancer and other advanced pelvic malignancies.
        Gynecol Oncol. 1999; 72: 45
        • Noda K.
        • Tanaka K.
        • Ozaki M.
        • et al.
        Early phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer. ETP 21 Study Group—Cervical-Ovarian Cancer Group.
        Jpn J Cancer Chemother. 1998; 25: 2061
        • Okamoto A.
        • Woodworth C.D.
        • Yen K.
        • et al.
        Combination therapy with podophyllin and vidarabine for human papillomavirus positive cervical intraepithelial neoplasia.
        Oncol Rep. 1999; 6: 269
        • Paavonen J.
        • Koutsky L.A.
        • Kiviat N.
        Cervical neoplasia and other STD-related genital and anal neoplasias.
        in: Holmes K.K. Mardh P.A. Sparling P.G. (eds): Sexually Transmitted Diseases. ed 2. McGraw Hill, New York1990: 561
        • Pfister H.
        The role of human papillomavirus in anogenital cancer.
        Obstet Gynecol Clin North Am. 1996; 23: 579
        • Phelps W.C.
        • Barnes J.A.
        • Lobe D.C.
        Molecular targets for human papillomaviruses: Prospects for antiviral therapy.
        Antiviral Chem Chemother. 1998; 9: 359
        • Quick C.A.
        • Watts S.L.
        • Krzyzek R.A.
        • et al.
        Relationship between condylomata and laryngeal papillomata. Clinical and molecular virological evidence.
        Ann Otol Rhinol Laryngol. 1980; 89: 467
        • Rando R.F.
        Human papillomavirus: Implications for clinical medicine.
        Ann Intern Med. 1986; 108: 628
        • Rao G.N.
        Influence of diet on tumors of hormonal tissues.
        Prog Clin Biol Res. 1996; 394: 41
        • Rose P.G.
        • Bundy B.N.
        • Watkins E.B.
        • et al.
        Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cancer.
        N Engl J Med. 1999; 340: 1144
        • Rosen C.A.
        • Woodson G.E.
        • Thompson J.W.
        • et al.
        Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis.
        Otolaryngol Head Neck Surg. 1998; 118: 810
        • Schafer K.
        • Muller M.
        • Faath S.
        • et al.
        Immune response to human papillomavirus 16 L1E7 chimeric virus-like particles: Induction of cytotoxic T cells and specific tumor protection.
        Int J Cancer. 1999; 81: 881
      1. Schneider A, Koutsky LA: Natural history and epidemiology features of genital HPV infection. In Munoz N, Bosch FX, Shah KV et al. (eds): The Epidemiology of Human Papillomavirus and Cervical Cancer. Lyon, 1992, p 25 IARC

        • Schneider A.
        • Kraus H.
        • Schuhmann R.
        • et al.
        Papillomavirus infection of the lower genital tract: Detection of viral DNA in gynecological swabs.
        Int J Cancer. 1985; 35: 443
        • Schneider A.
        • Meinhardt G.
        • Kirchmayr R.
        • et al.
        Prevalence of human papillomavirus genomes in tissues from the lower genital tract as detected by molecular in situ hybridization.
        Int J Gynecol Pathol. 1991; 10: 1
        • Schneider A.
        • Shah K.
        The role of vitamins in the etiology of cervical neoplasia: An epidemiological review.
        Arch Gynecol Obstet. 1989; 246: 1
        • Schon H.J.
        • Grgurin M.
        • Szekeres T.
        • et al.
        A new mode of treatment of human papilloma virus associated anogenital lesions using a nonsteroid estrogen analogue.
        Wien Klin Wochenschr. 1996; 108: 45
        • Shadan F.F.
        • Cowsert L.M.
        • Villarreal L.P.
        n-Butyrate, a cell cycle blocker, inhibits the replication of polyomaviruses and papillomaviruses but not that of adenoviruses and herpesviruses.
        J Virol. 1994; 68: 4785
        • Snoeck R.
        • Wellens W.
        • Desloovere C.
        • et al.
        Treatment of severe laryngeal papillomatosis with intralesional injections of cidofovir [(S)-l-(3-hydroxy-2-phosphonylmethoxypro-pyl)cytosine].
        J Med Virol. 1998; 54: 219
        • Spitzer M.
        Lower genital tract intraepithelial neoplasia in HIV-infected women: Guidelines for evaluation and management.
        Obstet Gynecol Surv. 1999; 54: 131
        • Spitzer M.
        • Krumholz B.A.
        Human papillomavirus-related diseases in the female patient.
        Urol Clin North Am. 1992; 19: 71
        • Spitzer M.
        • Krumholz B.A.
        • Chernys A.E.
        • et al.
        Comparative utility of repeat Papanicolaou smears, cervicography, and colposcopy in the evaluation of atypical Papanicolaou smears.
        Obstet Gynecol. 1987; 69: 731
        • Stone K.M.
        Human papillomavirus infection and genital warts: Update on epidemiology and treatment.
        Clin Infect Dis. 1995; 20: S91
        • Syrjanen K.J.
        Papillomavirus infections and cancers.
        in: Syrrjanen K. Gissmann L. Koss L.G. Papillomaviruses and Human Disease. Springer, New York1987: 467
        • Telang N.T.
        • Katdare M.
        • Bradlow H.L.
        • et al.
        Inhibition of proliferation and modulation of estrogen metabolism: Novel mechanisms for breast cancer prevention by the phytochemical indole-3-carbinol.
        Proc Soc Exp Biol Med. 1997; 216: 246
        • Thompson H.S.
        • Davies M.L.
        • Holding F.P.
        • et al.
        Phase I safety and antigenicity of लA-GW: A recombinant HPV6 L2E7 vaccine for the treatment of genital warts.
        Vaccine. 1999; 17: 40
        • Tindle R.W.
        Immunmanipulative strategies for the control of human papillomavirus associated cervical disease.
        Immunol Res. 1997; 16: 387
        • VanDriel W.J.
        • Ressing M.E.
        • Brandt R.M.
        • et al.
        The current status of therapeutic HPV vaccine.
        Ann Med. 1996; 28: 471
        • Venturini F.
        • Braspenning J.
        • Homann M.
        • et al.
        Kinetic selection of HPV 16 E6/E7-directed antisense nucleic acids: Anti-proliferative effects on HPV 16-transformed cells.
        Nucleic Acids Res. 1999; 27: 1585
        • Verdon M.E.
        Issues in the management of human papillomavirus genital disease.
        Am Fam Physician. 1997; 55: 1545
        • Werness B.A.
        • Levine A.J.
        • Howley P.M.
        Association of human papillomavirus type 16 and 18 E6 proteins with p53.
        Science. 1990; 248: 76
        • Yee C.
        • Krishnan-Hewlett Z.
        • Baker C.C.
        • et al.
        Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines.
        Am J Pathol. 1985; 119: 361
        • Yuan F.
        • Chen D-Z
        • Liu K.
        • et al.
        Anti-estrogenic activities of indole-3-carbinol in cervical cells: Implication for prevention of cervical cancer.
        Anticancer Res. 1999; 19: 1673
        • Zabawski Jr, E.J.
        • Cockerell C.J.
        Topical and intralesional cidofovir: A review of pharmacology and therapeutic effects.
        J Am Acad Dermatol. 1998; 39: 741
        • Zarcone R.
        • Bellini P.
        • Carfora E.
        • et al.
        Therapeutic protocol of vulvar and cervical HPV-infection.
        Clin Exp Obstet Gynecol. 1997; 24: 93
        • zur Hausen H.
        • Schneider A.
        The role of papillomaviruses in human anogenital cancers.
        in: Salzman N.P. Howley P.M. The Papovaviridae. ed 2. Plenum Press, New York1987: 245