A review of the development of nitric oxide as a topical treatment for cervical intraepithelial neoplasia caused by high-risk human papillomavirus infection

Persistent human papillomavirus (HPV) infection, especially of the high-risk (HR) HPV-16 and HPV-18 types, is linked to anogenital and oropharyngeal cancer. In women, HR-HPV infections of the cervix lead to growth of precancerous cervical intraepithelial neoplasias (CIN) before onset of invasive cervical cancer. Low incidence of widespread, preventive HPV vaccination and the disadvantages of surgical CIN excision (e.g., recurrence rates, pain, and risk of complications in future pregnancies) highlight the need for novel treatments to target HPV infection. Nitric oxide (NO) is a small molecule gaseous species with potent antiviral activity. This review of the preclinical and clinical development of nitric oxide-based topical treatments by Novan, Inc and others supports that NO delivery to the site of infection has the therapeutic potential to manage HPV infection and CIN.