Impact of an enhanced screening program on the detection of non-AIDS neoplasias in patients with human immunodeficiency virus infection
Authors: Masiá M. , Padilla S. , Estañ G. , Portu J. , Silva A. , Rivero A. , González-Cordón A. , García-Fraile L. , Martínez O. , Bernal E. , Galera C. , Boix Martínez V. , Macias J. , Montero M. , García-Rosado D. , Vivancos-Gallego M. J. , Llenas-García J. , Torralba M. , García J. A. , Agulló V. , Fernández-González M. , Gutiérrez F. , Martínez E. ,   IMPAC-NEO Study Group, Alcaraz-García Antonia , Caicedo Ana , Inciarte Alexy , Espinosa Alfredo , López-Lirola Ana , Amador Concha , Silva Ana , Navarro Antonio , Camacho Ángela , Pérez Aurora , Galera Carlos , Carreres Melissa , Piatti Camila , Vinuesa David , Dalmau David , García-Rosado Dácil , Diez-Martinez Marcos , Podzamczer Daniel , Saez Ester , Fagúndez-Reloba Esther , García Federico , Flores Juan , García Gema , García-Abellán Javier , Guillén Lucía , Navarro Gema , González-Cuello Inma , Albendín Helena , Ruiz-Cáceres Inmaculada , Machuca Isabel , Santos Ignacio , Sobron Itziar , Losa Juan Emilio , Gómez-Sirvent Juan Luis , Blanco Jose Ramon , Macías Juan , Gainzarai Juan Carlos , Martínez Lorena , Mallolas Josep , Alonso-Socas María del Mar , Martínez-López Belén , Fernández Araceli , Hernández-Rodríguez María Jehovana , Moran Miguel Angel , Navarro Marta , Pascual Reyes , Pasquau Francisco , Callau Pilar , Portilla Joaquín , Robledano Catalina , Rojas Jhon , Pelazas Ricardo , Cuellar Sandra , Del Campo Santos , Calzado Sonia , Moreno Santiago , Scévola Sofía , Telenti Guillemo , Ortiz Zuriñe 
Published: November 2021

Abstract
Background
The incidence of non-AIDS defining cancer (NADC) is higher in people living with HIV (PLWH) than in the general population, and it is already one of the leading causes of death in the HIV-infected population. It is estimated that the situation will be aggravated by the progressive aging of PLWH. Early diagnosis through intensive cancer screening may improve the ability for therapeutic interventions and could be critical in reducing mortality, but it might also increase expenditure and harms associated with adverse events. The aim of this study is to evaluate an enhanced screening program for early diagnosis of cancer in PLWH compared to standard practice. The specific objectives are (1) to compare the frequency of cancer diagnosed at an early stage, (2) to analyze safety of the enhanced program: adverse events and unnecessary interventions, (3) to analyze the cost-utility of the program, and (4) to estimate the overall and site-specific incidence of NADC in PLWH.

Methods
We will conduct a multicenter, non-blinded, randomized, controlled trial, comparing two parallel arms: conventional vs enhanced screening. Data will be recorded in an electronic data collection notebook. Conventional intervention group will follow the standard of care screening in the participating centers, according to the European AIDS Clinical Society recommendations, and the enhanced intervention group will follow an expanded screening aimed to early detection of lung, liver, anal, cervical, breast, prostate, colorectal, and skin cancer. The trial will be conducted within the framework of the Spanish AIDS Research Network Cohort (CoRIS).

Discussion
The trial will evaluate the efficacy, safety, and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard of care practice. The information provided will be relevant since there are currently no studies on expanded cancer screening strategies in patients with HIV, and available data estimating cost effectiveness or cost-utility of such as programs are scarce. An enhanced program for NADC screening in patients with HIV could lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions, but it is critical to demonstrate that the benefits clearly outweigh the harms, before the strategy could be implemented.

Trial registration
ClinicalTrials.gov NCT04735445. Registered on 25 June 2019