Virological and serological predictors of high-grade anal intraepithelial neoplasia (HGAIN) in HIV-infected men who have sex with men (MSM)
Virological and serological predictors of high-grade anal intraepithelial neoplasia (HGAIN) in HIV-infected men who have sex with men (MSM)
Project
Since combination antiretroviral therapy (cART) became available, AIDS mortality among HIV-infected people has decreased substantially. Anal squamous cell cancer (SCC) is a non-AIDS defining malignancy that is now one of the most frequent malignancies among HIV infected. Among HIV-infected men who have sex with men (MSM) its incidence is even higher than that of cervical cancer in unscreened female populations. Like cervical cancer, anal SCC is caused by human papillomavirus (HPV) and pre-cancer stages of anal SCC, i.e. anal intraepithelial neoplasia (AIN), can be detected and treated. Unfortunately anal cytology is not suitable as a screening strategy because of its low sensitivity and specificity regarding high-grade AIN (HGAIN). In this project we will investigate whether a number of other promising biomarkers are predictive for HGAIN, i.e. persistent high-risk HPV infections; HPV anal viral load; and L1, E6, and E7 seropositivity. A cohort of 320 HIV-infected MSM from Amsterdam, who have been examined for HPV during a follow up period of 2 years, will be invited to undergo high resolution anoscopy. Abnormal tissue will be biopsied to make a diagnosis of HGAIN. Subsequently we will examine which of the selected biomarkers predict HGAIN.
Project details
Objectives
In this project we will identify biomarkers that predict HGAIN in HIV-infected MSM. Hereto we will use a cohort of 327 hiv positive MSM (H2M study).
The research questions are:
-1- Does a persistent anal high-risk HPV (hr-HPV) infection predict the presence of HGAIN?
-2- Does the HPV-type of a persistent anal hr-HPV infection predict the presence of HGAIN?
-3- Does the HPV viral load of an anal hr-HPV infection predict the presence of HGAIN?
-4- Do L1, E6, or E7 HPV-type specific antibodies predict the presence of HGAIN?
-5- Do HIV viral load, current CD4 count or nadir CD4 count predict the presence of HGAIN?
-6- Is the HPV type in an HGAIN lesion the same as the HPV type of the persistent anal infection in that individual?
The output are scientific publication and data for databases.
The outcomes will be better predictive measures for anal cancer.
Community groups
scientific community
patients with prestages of anal cancer
Background
Since combination antiretroviral therapy (cART) became available, AIDS mortality among HIV-infected people has decreased substantially. Anal squamous cell cancer (SCC) is a non-AIDS
defining malignancy that is now one of the most frequent malignancies among HIV infected. Among HIV-infected men who have sex with men (MSM) its incidence is even higher than that of cervical cancer in unscreened female populations.
Anal squamous cell cancer (SCC) is a non-AIDS
defining malignancy that is now one of the most frequent malignancies among HIV infected.Among HIV-infected men who have sex with men (MSM) its incidence is even higher than that of cervical cancer in unscreened female populations. Like cervical cancer, anal SCC is caused by human papillomavirus
(HPV) and pre-cancer stages of anal SCC, i.e. anal intraepithelial neoplasia (AIN), can be detected and treated. Unfortunately anal cytology is not suitable as a screening strategy because of its low sensitivity and specificity regarding high-grade AIN (HGAIN).