Remission of HPV-Related Diseases by Antivirals for Herpesvirus: Clinical Cases and a Literature Review

Abstract

Epidemiological studies have shown that HPV-related diseases are the most prevalent sexually transmitted infections. In this context, this report will present various clinical cases demonstrating the effectiveness of Acyclovir (ACV) or its prodrug Valaciclovir (VCV), both acyclic guanosine analogs commonly used for the treatment of HHV-1 and HHV-2, for the treatment of HPV-related diseases. The report shows the remission of five cases of penile condyloma and a case of remission in a woman affected by cervical and vaginal condylomas and a vulvar giant condyloma acuminate of Buschke and Lowenstein. The literature review shows that ACV is effective in treating skin warts when administered orally, topically, and intralesionally, suggesting its therapeutic potential in other diseases associated with HPV. ACV was also used successfully as an adjuvant therapy for juvenile and adult forms of laryngeal papillomatosis, also known as recurrent respiratory papillomatosis, prolonging the patient's symptom-free periods. Although the prevention of HPV infections is certainly achieved with the HPV vaccine, ACV and VCV have shown to be effective even against genotypes not included in the current vaccine and can be helpful for those problematic clinical cases involving unvaccinated individuals, immunocompromised patients, people who live with HIV, or non-responders to the vaccine. We and others concluded that randomized clinical trials are necessary to determine the efficacy of ACV and VCV for HPV-related diseases.

Keywords: acyclovir and valaciclovir; condyloma; human papillomavirus; warts.

Figure 1

Colposcopy images of the ID5 patient’s vulva at the first visit (A); (B–D) are representative images showing GCBL remission during the ten months of follow-up. Image (E) shows the restitutio ad integrum after 1 and 2 years from the first visit.

Figure 2

Colposcopy images of ID5′s cervix after application of a 3% acetic acid solution. The histology test confirmed that the white lesion is a condyloma acuminata. Image (A): cervix at the first visit (10×); in the right panel, the sign of histological sampling; (B) images (5×) show the cervix during the treatment and the follow-up visits. (C) images (5×) show the restitutio ad integrum of the cervix after ten months after the first visit.

Figure 3

Vaginal condyloma acuminate of ID5.

Figure 4

Tryptophan (L-Trp) metabolism in mammalian cells. The enzymes affected by ACV are circled in red. IDO: indoleamine 2,3-dioxygenase; KAT: kynurenine aminotransferase; KYNU: L-kynurenine hydrolase; KMO: kynurenine 3-monooxygenase; 3-HAO: 3-hydroxyanthranilate-3,4-dioxygenas; ACMS: aminocarboxymuconate-semialdehyde decarboxylase; QPRT: quinolinate phosphoribosyl transferase; TPH2: tryptophan hydroxylase 2; AAAD: aromatic L-amino acid decarboxylase: SNAT: serotonin N-acetyltransferase; HIOMT: hydroxy indole-O-methyltransferase.