HIV protease inhibitors to prevent progression of cervical intraepithelial neoplasia to cervical cancer: Therapeutic opportunities and challenges

摘要

Human papillomavirus (HPV)-related cancers remain one the most common causes of cancer-related mortality worldwide [1]. HIV-infected women are at even higher risk of cervical cancers compared with HIV-uninfected women, and HIV-infected men and women are at increased risk of anal cancer compared with their HIV-uninfected counterparts [2—4]. HPV-associated cancers are largely preventable. Primary prevention is available through HPV vaccination to prevent cancers associated with vaccine HPV types (HPV 16 and HPV 18) [5,6]. Secondary prevention is accomplished through detection of high-grade cancer precursors such as cervical intraepithelial neoplasia (CIN) or anal intraepithelial neoplasia (AIN) and physical removal/destruction of these lesions to prevent progression to cancer. These measures are effective for preventing cervical cancer and their efficacy is inferred, although not yet definitively established for anal cancer. Treatment of high-grade precancerous lesions is invasive and associated with side-effects such as pain, bleeding, scarring and, in the case of CIN treatment, premature delivery [7]. Better strategies for eradication of precancerous lesions are clearly needed. The article by Barilleri et at. [8] points to a new approach to treat HPV-associated precancerous lesions, employing protease inhibitors commonly used to treat HIV infection to inhibit matrix metalloproteinases (MMPs).