HPV Infection-Associated Cancers: Next-Generation Technology for Diagnosis and Treatment

Abstract

Disease caused by human papillomavirus (HPV) remains common, despite preventive vaccines and screening strategies. Globally, HPVs cause one third of infection-associated cancers. The indolent clinical course of the precursor intraepithelial lesions provides an opportunity to understand immunologic obstacles posed by the microenvironment of incipient disease, and how they might be overcome. Results from recent therapeutic HPV vaccine clinical trials suggest that relevant immune responses may be sequestered at the lesion site and are difficult to detect in the circulation. In this Cancer Immunology at the Crossroads article, we outline the current understanding of the risk, diagnosis, and treatment of HPV infection-associated cancers and suggest that quantitative tissue-based endpoints should be included whenever possible in the evaluation of immune-based therapies.

Figure 1

Colposcopic appearance of cervical intraepithelial neoplasia 2/3 CIN2/3. Sharply demarcated, dense acetowhite lesion, with pathognomonic pattern of neovasculature, termed “mosaicism”. Adapted from Trimble et al. (25). (Originally published in The Journal of Immunology Trimble CL, Clark RA, Thoburn C, Hanson NC, Tassello J, Frosina D, et al. Human papillomavirus 16-associated cervical intraepithelial neoplasia in humans excludes CD8 T cells from dysplastic epithelium. J Immunol. 2010;185:7107-14. Copyright © 2010 The American Association of Immunologists, Inc.)