CANCER SCREENING IN HIV-INFECTED PATIENTS: EARLY DIAGNOSIS IN A HIGH-RISK POPULATION - World Cancer Research Journal

Abstract

Objective: With the introduction of the antiretroviral therapy (ART) in 1996, life expectancy of the patients infected with HIV almost approached that of the general population. Immune dis-regulation increases not only the risk of developing a neoplasm, but also its progression rate and aggressiveness. Several recent studies suggest a synergistic carcinogenic effect of aging and the HIV virus. The aim of this study was to obtain data about cancer screening of the HIV-positive patients followed in our center. Patients and Methods: Patients and controls were asked to reply to a survey after signing an informed consent. Data were registered into an electronic database in Excel format and analyzed using the IBM Statistical Package for Social Science software (Chicago, IL, USA) for Windows, version 25.0. Results: One hundred and nine individuals (53 HIV-positive cases, 48.6%, and 56 HIV-negative controls, 51.4%) were included in the study. Ninety-four (86.2%) were males. Fourteen cases and 14 controls received a proposal to undergo a screening test during their lifetime. Of these, only ten cases and 10 controls underwent them, with an overall adherence of 18.9% both in cases and controls. Seventeen cases and 20 controls met the criteria for prostate cancer screening, 2 cases and 5 controls should have been proposed the breast cancer screening, 32 cases and 10 controls were eligible for colorectal cancer screening, 11 cases and 4 controls should have undergone lung cancer screening, 5 cases and 8 controls should have undergone PAP test at least once in their life, 27 cases and 4 controls were eligible for anal cancer screening. Conclusions: A low percentage of patients underwent any screening test for cancers, as well as a very low percentage of controls, not only in the HIV positive population, but also in the control group. General practitioners and the infectious specialists hold the opportunity to propose and promote cancer screening tests as an integral part of the clinical management of patients, especially if at high risk, such as PLWH.

Full text

1
CANCER SCREENING IN HIV-INFECTED
PATIENTS: EARLY DIAGNOSIS
IN A HIGH-RISK POPULATION
WCRJ 2018; 5 (3): e1130
Corresponding Author: Giuseppe Nunnari, MD, PhD, MPH; e-mail: gnunnari@unime.it
Abst ract – Objective: With the introduction of the antiretroviral therapy (ART) in 1996, life
expectancy of the patients infected with HIV almost approached that of the general population.
Immune dis-regulation increases not only the risk of developing a neoplasm, but also its progres-
sion rate and aggressiveness. Several recent studies suggest a synergistic carcinogenic effect of
aging and the HIV virus. The aim of this study was to obtain data about cancer screening of the
HIV-positive patients followed in our center.
Patients and Methods: Patients and controls were asked to reply to a survey after signing an in-
formed consent. Data were registered into an electronic database in Excel format and analyzed using the
IBM Statistical Package for Social Science software (Chicago, IL, USA) for Windows, version 25.0.
Results: One hundred and nine individuals (53 HIV-positive cases, 48.6%, and 56 HIV-negative
controls, 51.4%) were included in the study. Ninety-four (86.2%) were males. Fourteen cases and
14 controls received a proposal to undergo a screening test during their lifetime. Of these, only
ten cases and 10 controls underwent them, with an overall adherence of 18.9% both in cases and
controls. Seventeen cases and 20 controls met the criteria for prostate cancer screening, 2 cases and
5 controls should have been proposed the breast cancer screening, 32 cases and 10 controls were
eligible for colorectal cancer screening, 11 cases and 4 controls should have undergone lung cancer
screening, 5 cases and 8 controls should have undergone PAP test at least once in their life, 27 cases
and 4 controls were eligible for anal cancer screening.
Conclusions: A low percentage of patients underwent any screening test for cancers, as well as a very
low percentage of controls, not only in the HIV positive population, but also in the control group. General
practitioners and the infectious specialists hold the opportunity to propose and promote cancer screening
tests as an integral part of the clinical management of patients, especially if at high risk, such as PLWH.
KEYWORDS: Cancer, HIV, Screening, Screening test, Adherence, Screening program.
1Department of Clinical and Experimental Medicine, Unit of Infectious Diseases, University of Messina,
Messina, Italy
2Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania,
Philadelphia, PA, USA
3Department of Clinical and Experimental Medicine, Unit of Infectious Diseases, University of Catania, Catania, Italy
4Hospital for the Emergency “Tommaso Cannizzaro”, Unit of Infectious Diseases, Catania, Italy
5Department of Civil Engineering and Architecture, University of Catania, Catania, Italy
6Department of Human Pathology of the Adult and the Developmental Age “G. Barresi”, Unit of Oncology,
University of Messina, Messina, Italy
7Department of Human Pathology of the Adult and the Developmental Age “G. Barresi”, Unit of Infectious
Diseases, University of Messina, Messina, Italy
Flavia D’Andrea and Manuela Ceccarelli equally contributed to this study
F. D’A N DRE A
1
, M. CECCARELLI
1
, E. VENANZI RULLO
1,2
, A. FACCIOLÀ
1
, F. D’ALEO
1
,
B. CACOPARDO
3
, C. IACOBELLO
4
, A. COSTA
5
, G. ALTAVILLA
6
, G. F. PELLICANÒ
7
,
G. NUNNARI
1

2
CANCER SCREENING IN PEOPLE LIVING WITH HIV
istered into an electronic database in Excel format
and analyzed using the IBM Statistical Package for
Social Science software (SPSS Inc., Chicago, IL,
USA) for Windows, version 25.0. Descriptive sta-
tistics were used to analyze data. Frequency and
percentages were used to resume categorical vari-
ables, while mean ± standard deviation (SD) to re-
sume continuous variables. Pearson’s c2-test (Con-
dence Interval, CI, 95%) was used to determine
statistically signicant differences between a case
HIV-positive population and a control HIV-negative
population.
RESULTS
One hundred and nine individuals (53 HIV-positive
cases, 48.6%, and 56 HIV-negative controls, 51.4
%) were included in the study. Ninety-four (86.2%)
were males, 46/53 (86.8%) cases and 48/56 (85.7
%) controls, 13 females (11.9%), 5/53 (9.4%) cases
and 8/56 (14.3%) controls; 2/53 (3.8%) were female
transsexuals. Mean age of the cohort included in
the study was 46.0 years (SD ± 12.4 years). Cases
were slightly younger (45.3 ± 11.5 years) than con-
trols (46.7 ± 13.2 years). There were no statistically
signicant differences between cases and controls
regarding gender ( p = 0.265) or age (p = 0.569). Re-
garding sexual orientation, a statistically signicant
difference ( p < 0.001) existed between cases and
controls, with cases including more homosexual and
bisexual people than controls.
Characteristics of the population are resumed in Ta-
ble 1.
With regards to risk factors, smoking was the
most frequent one, with a statistically signicant
difference existing between cases, with 66.0%
smokers, and controls, with 19.6% smokers (p <
0.001). Moreover, controls were more prone to quit
smoke, with a mean duration of the smoke habit be-
fore dismission in HIV-positive people of 26.4 years
(SD ± 8.0 years) against 12.6 years (SD ± 11.7) in
controls (p = 0.001). No statistical difference was
found regarding the number of cigarettes smoked
per day, the number of quitters and the number of
cigarettes smoked per day before quitting. We also
investigated hormonal contraception, radiological
testing before the age of 30 years, and the use of
corticosteroid drugs. No statistical difference was
found between cases and controls. Fourteen cases
and 14 controls received a proposal to undergo a
screening test during their lifetime. Of these, only
ten cases and 10 controls underwent them, with an
overall adherence of 18.9% both in cases and con-
trols. The proposal was made more often by the
infectious diseases specialist with regards to cases,
while the Provincial Health Authority was the most
INTRODUCTION
With the introduction of the antiretroviral therapy
(ART) therapy in 1996, life expectancy of the pa-
tients living with HIV (PLWH) almost approached
that of the general population1,2 . This lengthening
brought to an increase in the incidence of chronic
diseases such as cancers, which epidemiology, how-
ever, has changed in the last twenty years3-24 . Th e in-
cidence of AIDS-dening cancers, such as Kaposi’s
Sarcoma (KS), Cervical cancer and Non-Hodgkin
Lymphomas (NHL) has signicantly decreased,
while an increase in Non-AIDS-Dening cancers
(NADCs) has been documented25- 43. Several recent
studies suggest a synergistic carcinogenic effect of
aging and the HIV virus: in addition to the “clas-
sic” risk factors such as smoking, alcohol and aging,
HIV-related risk factors such as immunodeciency,
chronic persistence of inammation and viral infec-
tions often associated with HIV for similar modes of
transmission (HBV, HCV, HPV) have to be consid-
ered44, 45. As a matter of fact, immune dis-regulation
increases not only the risk of developing a neoplasm,
but also its progression rate and aggressiveness34.
Therefore, it is of utmost importance preventing and
early recognizing cancers in PLWH to ensure them
better outcomes. The aim of this study was to obtain
data about cancer screening of the HIV patients fol-
lowed in our center, and to compare them with the
general population to nd the most recurrent risk
factors needing a greater attention.
MATERIALS AND METHODS
From October 3rd, 2 017, to Ja nu a ry 31st, 2018, patients
coming to the outpatient clinic of the Infectious Dis-
eases Unit of the University Hospital “G. Martino”
in Messina, Italy, were asked to reply to a survey
after signing an informed consent. The survey was
a two-parts questionnaire: the rst part asked for in-
formation about the patients’ general health status,
HIV serological status, familiar pathologies, drugs
taken, past pathologies, while the second one looked
into risk factors for cancers and the patients’ adher-
ence to screening tests, as dened by the “Italian
Guidelines for the use of the Antiretroviral Therapy
and diagnostic-clinical management of people liv-
ing with HIV-1 infection – 2017 edition”46. Partic-
ipation to the survey did not require the execution
of additional diagnostic tests or treatments; more-
over, we guaranteed anonymity and there was an
opt-out chance not leading to any repercussions on
medical-care continuity. No inclusion or exclusion
criteria were used. Patients’ and controls’ were iden-
tied using their HIV serological status (positive for
patients and negative for controls). Data were reg-

3
CANCER SCREENING IN PEOPLE LIVING WITH HIV
among the 15 people (11/53 cases, 20.8%, 4/56 con-
trols, 7.1%) that met the criteria for inclusion in the
screening, only 7/11 cases (63.6%) and no control
underwent the test. This difference was statistically
signicant ( p = 0.003). However, patients and con-
trols did not undergo the CT-scan for lung cancer
screening: 14/32 cases (43.8%) had a chest CT-scan
done for a suspect of infectious disease (bronchitis,
pneumonia, tuberculosis), while 18/32 cases (56.2%)
underwent a CT-scan for other reasons (trauma,
rheumatological disorders, gastro-intestinal disor-
ders); 100% of the controls underwent the examina-
tion for a suspect of infectious disease. Papanicolau
test (PAP-test) for cervical cancer screening was
performed only in 9 of the 13 women (3/53 cases,
5.7%, 6/56 controls, 10.7%) included in the study,
who were all eligible for the proposal of the screen-
ing test. Only one of the people that met the criteria
for inclusion in the anal cancer screening (anal PAP-
test), 27/53 cases, 50.9%, and 4/56 controls, 7.1%,
underwent it.
Details about the percentages of the screening
tests carried out in patients and controls are re-
sumed in Table 2.
inuential among the controls. With regards to pros-
tate cancer screening, 17/53 cases (32.1%) and 20/56
controls (35.7%) met the criteria for inclusion. Only
8/17 cases (47.1%) and 7/20 controls (35.0%) under-
went a Specic Prostatic Antigen (SPA) dosing and
a Digital Rectal Exploration (DRE). No statistical-
ly signicant differences were found (p = 0.46).
Among the 13 women included in the population,
7 met the criteria to be screened for breast cancer,
2 cases and 5 controls, and 6 of them (2 cases and 4
controls) underwent the recommended test. Of note,
also 3 women not meeting the criteria, 2 cases and
1 control, underwent mammography. No statistical
analysis was performed.
Forty-two of 109 (38.5%) individuals included in
the study, 32/53 (60.4%) cases and 10/56 (17.9 %) co n -
trols, were eligible for colon-rectum cancer screen-
ing with fecal occult blood (FOB). However, only
5/32 cases (15.6%) and 5/10 controls (50.0%) under-
went it. Of note, 14 people, 10/53 cases (18.9%), 4/56
controls (7.1%) not meeting the criteria underwent
the screening. Curiously, a chest CT-scan was per-
formed in 38 people included in the study, 32/53
cases (60.4%) and 6/56 (10.7%) controls. Of interest,
TABLE 1. Characteristics of the population.
Cases (%) Controls (%) p-value
Comorbidities
None 15/53 (28.3%) 27/56 (48.2%) 0.070
1-3 37/53 (69.8%) 29/56 (51.8%)
> 3 1/53 (1.9%) 0
Previous cancer
None 48/53 (90.6%) 53/56 (94.6%) Not performed
Yes 5/53 (9.4%) 3/56 (5.4%)
Familiar pathologies
None 24/53 (45.3%) 26/56 (46.4%) 0.993
1-3 28/53 (52.8%) 21/56 (51.8%)
> 3 1/53 (1.8%) 1/56 (1.8%)
Drugs (other than cART)
None 33/53 (62.3%) 35/56 (62.5%) 0.480
1-3 14/53 (26.4%) 18/56 (32.1%)
> 3 6/53 (11.3%) 3/56 (5.4%)
TABLE 2. Patients and controls who were eligible for screening and underwent it.
*No one underwent the test for screening reasons
Cancer Patients eligible Patients who Controls eligible Controls who
for screening underwent screening for screening underwent screening
(%) (%) (%) (%)
Prostate 17/53 (32.1%) 8/17 (47.1%) 20/56 (35.7%) 7/20 (35.0%)
Breast 2/53 (3.8%) 2/2 (100%) 5/56 (8.9%) 4/5 (80.0%)
Colorectal 32/53 (60.4%) 5/32 (15.6%) 10/56 (17.9%) 5/10 (50.0%)
Lung 11/53 (20.8%) 7/11 (63.6%) * 4/56 (7.1%) 0/4 (0.0%)
Cervical Cancer 5/53 (9.4%) 3/5 (60.0%) 8/56 (14.3%) 6/8 (75.0%)
Anal Cancer 27/53 (50.9%) 1/27 (3.7%) 4/56 (7.1%) 0/4 (0.0%)

4
CANCER SCREENING IN PEOPLE LIVING WITH HIV
Authors’ contri butions:
FDAn, MC and EVR wrote the article; GA, CI, FDAn,
FDAl and AF recruited the patients; AC performed the
statistical analysis; GN, BC and GFP revised the man-
uscript.
Fundings:
This research was funded with the 2016 Gilead Fellowship
Program grants, project identier b5318762615.
inFormed consent:
Cases and controls signed a standard form of consent,
expressing their informed consent for the scientic use of
their clinical data.
conFlict oF in terest:
Th e aut ho rs de cl are th at th ey have no con ict of inte rests .
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DISCUSSION
The introduction of ART has had a signicant im-
pact on PWLH survival. As a consequence, we as-
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dening cancers, and a relative decrease in AIDS
de ning ones, thus highlighti ng the need for screen-
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not possible47-49. Screening tests, when available,
represent an effective weapon in cancer prevention,
together with an early onset of therapy, lifestyle
changes, coinfection treatment and vaccinations. To
understand the needs of the patients we follow on
a daily basis in our outpatient clinic, we decided to
investigate risk factors for cancer, evaluate the pro-
motion and adherence to screening programs, com-
paring HIV+ patients with the general population.
Statistically signicant differences highlighted by
our study among PLWH and the general population
do not differ from the epidemiology of the HIV infec-
tion5 0, 51. HIV affects more non-heterosexual people
than heterosexual ones, PLWH are more often smok-
ers than the general population, and less prone to
quit the habit. However, surprisingly, we did not nd
many statistically signicant differences in the num-
ber of proposals to undergo screening tests. As the
HIV infection is an anonymous condition, no differ-
ence should be made regarding selection, but PLWH
were thought to access cures more frequently than
the general population, and thus, to undergo screen-
ing tests more often than them. Moreover, not every
patient who was counselled to undergo a screening
test actually put through with it. Thus, we have to
put a new attention on the problem: maybe our com-
munication is not so effective, and we have to spend
more time with our patients to persuade them of the
importance of screening and early diagnosis. Hope-
fully, raising our awareness to this disappointing rate
of screening tests performed in PLWH in the future
we will assist to a decline in NADCs as we assisted to
a decrease in the rate of ADCs.
CONCLUSIONS
The promotion of screening tests is essential: despite
their existence, however, only a low percentage of
patients underwent any screening test for cancers,
as well as a very low percentage of controls, not
only in the HIV positive population, but also in the
control group.
General practitioners and the infectious specialists
hold the opportunity to propose and promote cancer
screening tests as an integral part of the clinical man-
agement of patients, especially if at high risk, such as
PLWH. The introduction of HIV-specic screening
strategies for certain cancers should be considered.

5
CANCER SCREENING IN PEOPLE LIVING WITH HIV
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