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HPV infections

Wednesday 19 November 2014

Lower anogenital tract

Human papillomavirus (HPV) infection of the lower anogenital tract (LAT) has long been implicated in the precancerous and cancerous lesions of the epithelia of those organs.

HPV DNA is identified in almost all cervical cancer cases.

Different HPV subtypes were found to have a different carcinogenic potential and are generally classified into two different categories: low-risk (HPV 6 and 11 cause up 90% of genital warts), and high-risk (HPV 16 and 18 associated with up to 70% of all cervical cancer).

In lesions associated with low-risk HPV infection, there is transient virion production by the infected squamous cells, manifested histologically by mild dysplasia or condyloma.

In lower genital tract precancerous and cancerous lesions associated with high-risk HPV infection, there is an integration of the HPV genome into the host DNA that leads to the overproduction of the E6 and E7 oncogenes and subsequently cell clonal proliferation.

The Rb gene is inactivated by HPV E7oncoprotein that lead to over-production of p16 protein that is normally inhibited by the Rb gene.

Overexpression of p16 is present in over 99% of high-grade squamous intraepithelial lesion (HSIL) and can be demonstrated by immunohistochemistry (IHC).

LAST Project

The College of American Pathologists (CAP) and the American Society for Colposcopy and Cervical Pathology (ASCCP) have published a new recommendation for the terminology for human papillomavirus-associated squamous lesions of the lower anogenital tract (LAST Project) and evaluated the use of molecular markers in conjunction with H&E morphology, including p16, Ki-67 (Mib1), ProEx, L1, HPV 16/18 mRNA, telomerase/TERC, and HPV. Based on literature review and evaluation of the data, the working group for the LAST Project (WG4) concluded that only p16 had sufficient evidence on which to make recommendations regarding its use as an adjunct to morphologic assessment for LAT biopsy specimens.