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CANCER IN PEOPLE LIVING WITH HIV-AIDS AT A REFERRAL HOSPITAL IN LIMA, PERU

This study was carried out to describe and compare the demographic, clinical, and therapeutic characteristics of HIV patients who developed some cancer. We identified 276 cancer cases diagnosed at Hospital Cayetano Heredia between 2000 and 2018. 80,8% (223/276) had AIDS-defining-cancers (ADCs), being Kaposi's Sarcoma the most frequent type; meanwhile, among non-AIDS-defining-cancers (NADCs), the most frequent was Hodgkin lymphoma. The median age was 36,5 years, being highest among the cases diagnosed with NADCs. Concerning CD4 lymphocyte counts, the median among ADCs was much lower than NADCs, 87,5 cells/μl and 216 cells/μl, respectively. Therefore, NADCs cases have a longer history of HIV infection, and an older age at cancer diagnosis, as well as higher CD4 cells counts.


INTRODUCTION
The risk of developing cancer in people living with HIV (PLHIV) is higher than that of the general population; this is a consequence of the immunosuppression caused by this virus, which impairs the control of viral infections with oncogenic potential (1,2) . After the introduction of antiretroviral therapy (ART) worldwide, the morbidity and mortality rate due to opportunistic infections and some cancers decreased considerably (3) . In developed countries, where this therapy is widely available, PLHIV have a longer life expectancy and neoplasms are positioned as one of the main causes of death (4) .
According to the Centers for Disease Control and Prevention (CDC) classification criteria (5) , HIV-associated cancers are classified into AIDS-defining neoplasms (ADN) and non-AIDSdefining neoplasms (NADN). ADN include Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL) and invasive cervical cancer (ICC), all caused by oncogenic viruses such as human herpes virus type 8 (HHV-8), Epstein-Barr virus (EBV) and human papillomavirus (HPV), respectively (5) . And NADN include all remaining types of cancers. Thus, since the widespread use of ART, the incidence of ADN has largely decreased, while the number of NADN has increased in recent years (6,7) .
In Peru there is little evidence on neoplasms in PLHIV. Of the few articles, those on KS and non-Hodgkin's lymphoma stand out. For example, Mohanna et al. found an incidence of KS of 20 per 1,000 patients treated for HIV between 1987 and 2003 (8) . While, in 2018, Cuellar et al. carried out a study to determine prognostic factors for non-Hodgkin's lymphoma in HIV patients.

KEY MESSAGES
To date, there is not a study that describes the characteristics of HIV patients who developed any type of cancer (9) . Therefore, much of the information comes from studies conducted in other countries, where the epidemiological characteristics and the context of the population are different from those in Peru (10)(11)(12) . For this reason, the aim of our study was to describe and compare the demographic, clinical, and therapeutic characteristics of PLHIV who developed cancer in a public referral hospital in Peru.  HIV diagnosis to cancer. Cancer diagnosis was taken into account up to one year prior to HIV diagnosis, and at any time after HIV diagnosis (13) .

Design and study population
Laboratory values were CD4 cell count (<200 cells/μL or ≥200 cells/μL) and Log 10 viral load (suppressed; 2.6-3.9; 4.0-4.9 or ≥5.0 copies/mL), both based on the most recent result registered between six months before and one month after the date of cancer diagnosis (13) . Cancer treatment comprised chemotherapy, radiotherapy, surgery, or a combination thereof.
Intraepithelial neoplasms (CIN) were not considered. Missing data were kept and classified in the unknown group.

Data Management
The information was obtained through authorized extraction from the COVIHS database. Personal data such as names and surnames were associated with a numerical code. Subsequently, a new database was created in Excel, respecting the same numerical identifiers. Only the researchers had access to the final database, and the main researchers were responsible for its processing and statistical analysis. To guarantee the quality of the information, we verified for inconsistencies, errors and duplicate data.

Statistical analysis
Descriptive analysis was summarized using median and interquartile range (IQR) for continuous variables, and percentages for categorical variables. To compare variables between the ADN and NADN groups, we applied the Chisquare test and the Mann-Whitney U test, as appropriate.
A p value of less than 0.05 was considered statistically significant. Data harmonization and processing was carried out with the STATA 14 statistical package.

Ethical considerations
The study protocol was approved by the Institutional Ethics Committee of the Universidad Cayetano Heredia. Informed consent was not required because the data came from a database and was analyzed retrospectively.  Figure 1 shows how the number of cancer cases has been increasing over the years, with ADN cases predominating over NADN.

DISCUSSION
This study demonstrates that ADN were the most frequent  (1,14,15) , where AND cases were found to be the predominant group; however, some recent reports from developed countries have shown that the incidence of NADN has increased (6,7) . According to previous reports (12,14) , KS was the most common neoplasm among ADN, particularly in places where co-infection with HHV-8 is high, such as in Latin America and Africa. Whereas, among NADN, Hodgkin's lymphoma (HL) was the most frequent, as seen in other countries (16) .

Regarding demographic characteristics, in concordance
with other studies (17,18) , PLHIV were diagnosed with NADN at an older age than ADN; however, it is still a very young age to develop cancer compared to the general population without HIV. Similar to a previous report (19) , cases in males were more frequent than in females; however, some studies in Africa have shown that cancer frequencies were comparable or even higher in females because of the higher incidence of HIV among females. Due to the high prevalence of co-infection with HHV-8 among MSM, this population was more likely to belong to the ADN group. On the other hand, although in our series the presence of a second cancer diagnosis was low (seven cases), we noted that most of them were HHV-8 and EBV-related infections.