Correspondence

Treatment of Anogenital Papillomavirus Infections with an Acyclic Nucleoside Phosphonate Analogue

N Engl J Med 1995; 333:943-944October 5, 1995

Article

To the Editor:

(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) is an acyclic nucleoside phosphonate analogue with broad-spectrum antiviral activity against DNA viruses, including herpesviruses (herpes simplex virus, varicella–zoster virus, cytomegalovirus, and Epstein–Barr virus), adenoviruses, poxviruses, and papillomaviruses.1,2 We recently showed that local injections of HPMPC into a life-threatening squamous papilloma of the hypopharynx–esophagus eradicated the tumor.2 Two years later, the patient was still free of disease. We report the use of HPMPC in three patients with AIDS and severe, relapsing anogenital human papillomavirus lesions.

A 44-year-old homosexual man had been unsuccessfully treated for recurrent penile human papillomavirus lesions since December 1993 with curettage and local applications of podofilox. A biopsy confirmed the diagnosis of bowenoid papulosis. Six months later, the patient was treated with local applications of HPMPC (1 percent in Beeler base) once daily for five days. On day 7, he had small ulcerations at the original site of the human papillomavirus lesions. Scarring was noted. One month later, the patient had definitely recovered. He remained free of disease one year after treatment.

A 20-year-old homosexual man had recurrent exophytic perigenital and intraanal condylomata diagnosed in October 1993. One year later, he was seen for a fifth relapse. He had been receiving electrocoagulation therapy. HPMPC (1 percent in Beeler base) was applied once daily on the external lesions. By day 7, most of the lesions had disappeared; some local irritation was noted. The treatment was stopped after 11 days. The human papillomavirus lesions were replaced by mucosal erosions that were treated symptomatically. The erosions healed within one week. Six months later, no external lesions had recurred. The remaining intraanal lesions were surgically removed.

A 34-year-old African woman had had severe relapsing human papillomavirus lesions of the cervix and vulva since 1990. She had been treated on several occasions with laser vaporization. In August 1994 she noticed a marked relapse of the condylomata, involving the vulva and the perigenital skin, which was clinically suggestive of Bowen's disease. HPMPC (1 percent in gel) was applied once daily. Substantial improvement was noted after one week, although some of the vulvar lesions responded more slowly. The treatment was stopped after five weeks. During six months of follow-up, she did not have a relapse.

Human papillomavirus type 16 DNA was identified in the lesions of all three patients. The results of HPMPC treatment in these three immunocompromised patients with severe infections are consistent with our earlier observations on the activity of HPMPC in previously treated patients with relapsing lesions due to human papillomavirus. These data suggest that HPMPC should be considered, along with other approaches, for the treatment of severe human papillomavirus lesions.3,4

R. Snoeck, M.D.
M. Van Ranst, M.D.
G. Andrei, Ph.D.
E. De Clercq, M.D.
Katholieke Universiteit Leuven, B-3000 Leuven, Belgium

S. De Wit, M.D.
M. Poncin, M.D.
N. Clumeck, M.D.
St. Pierre University Hospital, B-1000 Brussels, Belgium

4 References

1. 1

   De Clercq E. Therapeutic potential of HPMPC as an antiviral drug. Rev Med Virol 1993;3:85-96
   CrossRef | Web of Science

2. 2

   Van Cutsem E, Snoeck R, Van Ranst M, et al. Successful treatment of a squamous papilloma of the hypopharynx-esophagus by local injections of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine. J Med Virol 1995;45:230-235
   CrossRef | Web of Science | Medline

3. 3

   Cowsert LM. Treatment of papillomavirus infections: recent practice and future approaches. In: Gissmann L, ed. Papillomaviruses. New York: S. Karger, 1994:226-30.
   

4. 4

   Cirelli R, Tyring SK. Major therapeutic uses of interferons. Clin Immunother 1995;3:28-87
   

Citing Articles (29)

Citing Articles

1. 1

   Anita Arora, Natalia Mendoza, Stephen K. Tyring. 2011. Antiviral Market Overview. .
   CrossRef

2. 2

   Zlatko Janeba, Milena Masojídková, Antonín Holý. (2010) Alternative synthesis of 9-{3-[(diisopropoxyphosphoryl)methoxy]-2-hydroxypropyl}adenine and its free phosphonates substituted at the C-8 position of purine base. Collection of Czechoslovak Chemical Communications 75:3, 371-381
   CrossRef

3. 3

   Antonio Mastrolorenzo, Claudiu T Supuran, Giuliano Zuccati. (2007) The sexually transmitted papillomavirus infections: clinical manifestations, current and future therapies. Expert Opinion on Therapeutic Patents 17:2, 173-211
   CrossRef

4. 4

   Robert Snoeck. (2006) Papillomavirus and treatment. Antiviral Research 71:2-3, 181-191
   CrossRef

5. 5

   Charles J.N. Lacey. (2005) Therapy for genital human papillomavirus-related disease. Journal of Clinical Virology 32, 82-90
   CrossRef

6. 6

   Nicolas Dupin. (2004) Genital warts. Clinics in Dermatology 22:6, 481-486
   CrossRef

7. 7

   Erik De Clercq. (2003) Potential of acyclic nucleoside phosphonates in the treatment of DNA virus and retrovirus infections. Expert Review of Anti-infective Therapy 1:1, 21-43
   CrossRef

8. 8

   D. J. Wiley, John Douglas, Karl Beutner, Tom Cox, Kenneth Fife, Anna‐Barbara Moscicki, Lynne Fukumoto. (2002) External Genital Warts: Diagnosis, Treatment, and Prevention. Clinical Infectious Diseases 35:s2, S210-S224
   CrossRef

9. 9

   Alfredo Rebora. (2002) Antiviral drugs: unapproved uses, dosages, or indications. Clinics in Dermatology 20:5, 474-480
   CrossRef

10. 10

    C Martinelli, A Farese, A Del Mistro, S Giorgini, I Ruffino. (2001) Resolution of recurrent perianal condylomata acuminata by topical cidofovir in patients with HIV infection. Journal of the European Academy of Dermatology and Venereology 15:6, 568-569
    CrossRef

11. 11

    R. Snoeck, M. Bossens, D. Parent, B. Delaere, H. Degreef, M. Van Ranst, J. C. Noël, M. S. Wulfsohn, J. F. Rooney, H. S. Jaffe, E. De Clercq. (2001) Phase II Double‐Blind, Placebo‐Controlled Study of the Safety and Efficacy of Cidofovir Topical Gel for the Treatment of Patients with Human Papillomavirus Infection. Clinical Infectious Diseases 33:5, 597-602
    CrossRef

12. 12

    K. Geerinck, G. Lukito, R. Snoeck, R. De Vos, E. De Clercq, Y. Vanrenterghem, H. Degreef, B. Maes. (2001) A case of human Orf in an immunocompromised patient treated successfully with cidofovir cream. Journal of Medical Virology 64:4, 543-549
    CrossRef

13. 13

    ALBERTO MATTEELLI, ANNA BELTRAME, SEVERO GRAIFEMBERGHI, MARIA ANTONIETTA FORLEO, MAURIZIO GULLETTA, GIUSEPPE CIRAVOLO, SIMONA TEDOLDI, CATIA CASALINI, GIAMPIERO CAROSI. (2001) Efficacy and Tolerability of Topical 1% Cidofovir Cream for the Treatment of External Anogenital Warts in HIV-Infected Persons. Sex Transm Dis 28:6, 343-346
    CrossRef

14. 14

    Suphannee Koonsaeng, Claire Verschraegen, Ralph Freedman, Michel Bossens, Andrzej Kudelka, John Kavanagh, Tul Sittisomwong, Erik DeClercq, Robert Snoeck. (2001) Successful treatment of recurrent vulvar intraepithelial neoplasia resistant to interferon and isotretinoin with cidofovir. Journal of Medical Virology 64:2, 195-198
    CrossRef

15. 15

    Sandra Liekens, Erik Verbeken, Erik De Clercq, Johan Neyts. (2001) Potent inhibition of hemangiosarcoma development in mice by cidofovir. International Journal of Cancer 92:2, 161-167
    CrossRef

16. 16

    V. Descamps, X. Duval, M. Grossin, B. Crickx, C. Leport. (2001) Topical cidofovir for bowenoid papulosis in an HIV-infected patient. British Journal of Dermatology 144:3, 642-643
    CrossRef

17. 17

    Antonín Holý, Ivan Votruba, Eva Tloušťová, Milena Masojídková. (2001) Synthesis and Cytostatic Activity of N-[2-(Phosphonomethoxy)alkyl] Derivatives of N6-Substituted Adenines, 2,6-Diaminopurines and Related Compounds. Collection of Czechoslovak Chemical Communications 66:10, 1545-1592
    CrossRef

18. 18

    D Calista. (2000) Topical cidofovir for severe cutaneous human papillomavirus and molluscum contagiosum infections in patients with HIV/AIDS. A pilot study. Journal of the European Academy of Dermatology and Venereology 14:6, 484-488
    CrossRef

19. 19

    Neil D. Christensen, Martin D. Pickel, Lynn R. Budgeon, John W. Kreider. (2000) In vivo anti-papillomavirus activity of nucleoside analogues including cidofovir on CRPV-induced rabbit papillomas. Antiviral Research 48:2, 131-142
    CrossRef

20. 20

    P. Redondo, M. Idoate, J.C. Galofre, T. Solano. (2000) Cidofovir inhibits growth of B16 melanoma cells in vivo. British Journal of Dermatology 143:4, 741-748
    CrossRef

21. 21

    Brian Berman, Andrew Weinstein. (2000) Treatment of warts. Dermatologic Therapy 13:3, 290-304
    CrossRef

22. 22

    Angel L. Allen, Elaine C. Siegfried. (2000) What’s new in human papillomavirus infection. Current Opinion in Pediatrics 12:4, 365-369
    CrossRef

23. 23

    Jianmin Duan, William Paris, Josie De Marte, Diana Roopchand, Tamara-Louise Fleet, Michael G Cordingley. (2000) Topical effects of cidofovir on cutaneous rabbit warts: treatment regimen and inoculum dependence. Antiviral Research 46:2, 135-144
    CrossRef

24. 24

    Robert Snoeck, Jean-Christophe Noel, Christine Muller, Erik De Clercq, Michel Bossens. (2000) Cidofovir, a new approach for the treatment of cervix intraepithelial neoplasia grade III (CIN III). Journal of Medical Virology 60:2, 205-209
    CrossRef

25. 25

    W Preiser, N Kapur, R Snoeck, R.W Groves, N.S Brink. (2000) No apparent effect of cidofovir in epidermodysplasia verruciformis. Journal of Clinical Virology 16:1, 55-57
    CrossRef

26. 26

    G. Gross. (1999) Do we need antivirals for genital herpes simplex virus and human papillomavirus infection?. International Journal of Antimicrobial Agents 12:1, 1-3
    CrossRef

27. 27

    E. De Clercq, G. Andrei, J. Balzarini, S. Hatse, S. Liekens, L. Naesens, J. Neyts, R. Snoeck. (1999) Antitumor Potential of Acyclic Nucleoside Phosphonates. Nucleosides and Nucleotides 18:4-5, 759-771
    CrossRef

28. 28

    Robert Snoeck, Willy Wellens, Christian Desloovere, Mark Van Ranst, Lieve Naesens, Erik De Clercq, Louw Feenstra. (1998) Treatment of severe laryngeal papillomatosis with intralesional injections of cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine]. Journal of Medical Virology 54:3, 219-225
    CrossRef

29. 29

    Lieve Naesens, Erik de Clercq. (1997) Therapeutic Potential of HPMPC (Cidofovir), PMEA (Adefovir) and Related Acyclic Nucleoside Phosphonate Analogues as Broad-Spectrum Anttviral Agents. Nucleosides and Nucleotides 16:7-9, 983-992
    CrossRef