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MVA E2 Recombinant Vaccine in the Treatment of Human Papillomavirus Infection in Men Presenting Intraurethral Flat Condyloma

A Phase I/II Study

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Abstract

Background

Human papillomavirus (HPV) is the etiologic agent for warts and cervical cancer. In Mexico, the death rate from cervical cancer is extremely high, and statistical data show that since 1990 the number of deaths is increasing. Condylomas and cancer of the penis are the most common lesions presented in men; bladder and prostate cancer in men are also associated with the presence of HPV. Since HPV is transmitted by sexual intercourse, treating both partners is necessary in order to eliminate the virus in the population. Approaches to this include preventative vaccines such as Gardasil®, and therapeutic vaccines to treat established infections in both men and women. This will be the only way to decrease the numbers of deaths due to this malignancy.

Patients and methods

We conducted a phase I/II clinical trial to evaluate the potential use of the recombinant vaccinia viral vaccine MVA E2 (composed of modified vaccinia virus Ankara [MVA] expressing the E2 gene of bovine papillomavirus) to treat flat condyloma lesions associated with oncogenic HPV in men. Fifty male patients with flat condyloma lesions were treated with either MVA E2 therapeutic vaccine or fluorouracil (5-fluorouracil). Thirty men received the therapeutic vaccine, at a total of 106 virus particles per dose, administered directly into the urethra once every week over a 4-week period. Twenty control patients were treated with 5% fluorouracil 1mL twice weekly over a 4-week period directly into the urethra. Reduction of lesions or absence of papillomavirus infection was monitored by colposcopy and histologic analysis. The immune response after MVA E2 treatment was determined by measuring the antibodies against the MVA E2 virus and by analyzing the lymphocyte cytotoxic activity against cancer cells bearing oncogenic papillomavirus. Presence of papillomavirus was determined by the Hybrid Capture® method.

Results

Twenty-eight of 30 patients showed no lesion or presence of papillomavirus as diagnosed by colposcopy and brush histologic examination after 4 weeks of MVA E2 treatment. These patients showed complete elimination of flat condyloma in the urethra and no acetowhite spots were detected over the prepuce. In two other patients the acetowhite spots and flat condyloma did not diminish. All patients developed antibodies against the MVA E2 vaccine and E2 protein, and generated a specific cytotoxic response against papilloma-transformed cells. Viral DNA was not detected in MVA E2-treated patients.

In the control group, 13 of 20 patients were free of lesions. Three of these patients had recurrence of lesions after 3 months of treatment and none of the patients developed specific antibodies against cancer cells. In contrast, patients treated with MVA E2 did not show any recurrence of lesions after 1 year of treatment. In addition, none of the patients had local or systemic adverse effects according to the WHO classification 1–4.

Conclusions

Therapeutic vaccination with MVA E2 proved to be very effective in stimulating the immune system against papillomavirus, and in generating regression of flat condyloma lesions in men.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgments

This work was funded by Virolab, S de RL de CV. The authors declare no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Hospital General de Tlalnepantla Clínica de Displasias, Valle Ceylán, México

    Antonio Albarran y Carvajal, Alfonso de la Garza, Benitez Jose Cecilio Cruz Quiroz, Eduardo Vazquez Zea, Ismael Díaz Estrada & Ernesto Mendez Fuentez

  2. FES Zaragoza, National Autonomous University of México, México City, México

    Mario López Contreras

  3. Hospital de Gineco Obstetricia, Instituto Mexicano del Seguro Social (IMSS), México City, México

    Alejandro Andrade-Manzano

  4. Hospital de la Mujer, Jacona, Zamora Michoacan, México

    Santiago Padilla

  5. Hospital Juárez de México, México City, México

    Axel Ramírez Varela

  6. Department of Molecular Biology, Virolab, S de RL de CV, Manta 671, Colonia Lindavista, Mexico

    Ricardo Rosales

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  1. Antonio Albarran y Carvajal
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  2. Alfonso de la Garza
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  3. Benitez Jose Cecilio Cruz Quiroz
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  5. Ismael Díaz Estrada
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  6. Ernesto Mendez Fuentez
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  8. Alejandro Andrade-Manzano
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  9. Santiago Padilla
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  10. Axel Ramírez Varela
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  11. Ricardo Rosales
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Correspondence to Ricardo Rosales.

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y Carvajal, A.A., de la Garza, A., Quiroz, B.J.C.C. et al. MVA E2 Recombinant Vaccine in the Treatment of Human Papillomavirus Infection in Men Presenting Intraurethral Flat Condyloma. BioDrugs 21, 47–59 (2007). https://doi.org/10.2165/00063030-200721010-00006

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