23/09/2021
HIV/AIDS and cancer exist as comorbidities, with malignancies previously
associated with HIV/AIDS, also known as the AIDS-defining cancers (ADCs), having
been documented to decrease, while the non-AIDS defining cancer (NADCs) are on
the rise. Since cancer is a highly heterogeneous disease, precision oncology as
the most effective cancer therapy is gaining attraction, and many newly
developed drugs have been designed to identify particular molecular features
that may help in the diagnosis and treatment of cancer.
Among these, biomarkers are specific and highly sensitive markers of
varied molecular nature that can be found and measured in blood or tissue. Cancer
biomarkers are discovered through using molecular and cellular methodologies
that focus on disease and drug mechanisms, which indicate the interaction of
novel therapies with their intended target or in the pathogenesis of the
disease itself. Biomarkers consist of genomic and proteomic patterns,
chromosomal abnormalities, epigenetic signatures, single genes or proteins.
This causes biomarkers to play a significant role in cancer screening, early
diagnosis, cancer stratification, efficacy prediction and adverse reactions,
making them a powerful tool also in prognosis and treatment.
Regarding HIV-infected individuals, it is important to point out that they
have an increased risk for developing cancer, mainly due to their immune system
being suppressed, frequent coinfection with oncogenic viruses and an increase
in risky behaviour such as poor lifestyle. Early detection of cancer biomarkers
in HIV-positive individuals would be useful to identify patients at high risk
of tumour development.
ADCs are fortunately on the decline since the introduction of the highly
active antiretroviral treatment (HAART) in 1996. Three of them are hot topics
for biomarker research:
Cervical cancer. It develops as a result of a persistent infection with
high-risk human papillomavirus (hrHPV) types, resulting in premalignant
precursor lesions also known as cervical intraepithelial neoplasia (CIN).
Grading of CIN lesions is vital for clinical management of patients and
specific biomarkers are required for accurate grading, diagnosis, and
ultimately effective treatment of CIN. Novel biomarkers for the diagnosis of
cervical cancer include, among others, the presence of HPV E6/E7 mRNA, since the
initiation and mediation of the oncogenic process of cervical cancer occurs by
the upregulation of HPV E6/E7 oncoproteins. The overexpression of these
oncoproteins serves as a biomarker for increased cervical cancer risk.
Non-Hodgkin Lymphoma (NHL). It is the second most common malignancy in
HIV-infected patients and is characterised by diffused large B-cell lymphoma
(DLBCL). The quality and quantity of affected lymph nodes for assessing
morphology and architecture are the first requirement in the diagnosis of NHL. Blood
count, white blood cells or platelet count tests are followed by pathological
tests such as flow cytometry or immunohistochemistry. Protein expression
biomarker Ki-67 or its antibody MIB-1 staining are used to identify aggressive
lymphomas as these may be indicating a high growth fraction of tumours. Ki-67
expression in DLBCL patients is associated with poor outcome and survival.
Lastly, HIV-associated Kaposi’s Sarcoma (HIV-KS) is a low-grade vascular
tumour which is associated with human herpesvirus-8 (HHV8)/KS-associated herpes
virus (KSHV) infection, and is the most frequent and aggressive type of
endothelial neoplasia. Lesion progression represents the expression of HHV8
latency that include factors such as latent nuclear antigen-1 (LANA-1),
cyclin-D1 and bcl-2. The immunohistochemical detection of HHV8 of fixed tissues
might be a diagnostic tool to differentiate KS.
Personalised medicine is the trend in cancer and in many other diseases.
Its core depends on the discovery and the development of biomarkers and, in the
case of HIV, a careful selection of sensitive and specific HIV-associated
cancer biomarkers is key to identify patients at most risk of tumour
development. These advancements will help improve the diagnosis, prognosis, and
ultimately treatment of the disease, which will translate into a better quality
of life for HIV-associated cancer patients.
Reference:
Dlamini Z, Mbele M, Makhafola TJ, et al. HIV-Associated Cancer Biomarkers: A Requirement for
Early Diagnosis. Int J Mol Sci. 2021; 22(15): 8127.
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