Banca de DEFESA: ÁLIFE DIÊGO LIMA SILVA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : ÁLIFE DIÊGO LIMA SILVA
DATE: 15/12/2023
TIME: 14:00
LOCAL: Sala de Videoconferência da Faculdade de Medicina - UFCA (campus Barbalha)
TITLE:

ASSOCIATION OF EPSTEIN-BARR VIRUS (EBV) WITH UTERINE CERVICAL
CARCINOMA: TRACKING, CHARACTERIZATION OF THE EXPRESSION PATTERN
OF LATENT TRANSCRIPTS AND RELATIONSHIP WITH HUMAN
PAPILLOMAVIRUS (HPV)

KEY WORDS:

EBV, HPV, Cervical lesions, Cervical carcinoma, EBER, BamHI-W.

PAGES: 129
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

Cervical cancer is the fourth most common malignancy among women worldwide. In Brazil,
excluding the cases of non-melanoma skin cancer, cervical carcer is the third most common
type of cancer. Studies have demonstrated the presence of Epstein-Barr virus (EBV) in
samples of squamous cell carcinomas, indicating a possible association between the infection
and the development of this neoplasm. Thus, the present study aimed to determine the
presence of EBV in carcinomas and pre-malignant lesions of the uterine cervix and its
association with the Human Papillomavirus (HPV), determinate the viral load in infected
cases, investigate the expression pattern of latent genes, compare the results of in situ
hybridization for EBER RNA (ISH-EBER) and for the viral genome (ISH-DNA), and
evaluate the occurrence of a 30bp deletion in the latent membrane protein 1 (LMP1) gene.
Methodology: 88 samples of cervical carcinoma, a product of hysterectomy, were included
in this study, 41 from the Oncology Center of the São Vicente de Paulo Hospital and
Maternity (HMSVP) and 47 from the Tumor Biobank of the Ceará Cancer Institute (ICC).
Fifty-one biopsy samples from outpatients were also included, including 12 non-neoplastic
lesions (polyps and cervicitis), 32 low-grade squamous intraepithelial lesions (LSIL), and 7
high-grade squamous intraepithelial lesions (HSIL). EBV was detected by polymerase chain
reaction (PCR), quantitative PCR (qPCR) to determine viral load, immunohistochemistry
(IHC) and ISH. HPV16 and 18 were also detected by PCR. Results: By PCR, the prevalence
of EBV in cervical carcinoma samples was 29.5%. Among them, 14.8% had EBV/HPV16
coinfection and 3.4% had EBV/HPV18 coinfection. In the outpatient samples, the EBV
prevalence was 7.8%. For HPV16 and HPV18 the prevalence was 17.6% and 2.0%,
respectively. There was no statistical significance for the presence of EBV in cervical
carcinomas and cervical lesions (P=0.761 and P=0,722). Among EBV-positive cervical
carcinomas by PCR, 57.7% of them presented a 30bp deletion of the LMP1 viral gene, while

among cervical lesions this rate was 25% (OR=4,09). In qPCR analysis, 90.9% of poorly
differentiated tumors were positive for EBV. The analysis of the average viral load with
differentiation grade and tumor staging revealed statistical significance, with P=0.008 and
P=0.002, respectively, demonstrating that poorly differentiated tumors in stages I and II had
the highest viral loads. By ISH-EBER, EBV was detected in 12.5% of cervical carcinomas.
However, by ISH-DNA 50% of cervical carcinomas were positive for EBV. Conclusions:
The EBV detection rate was higher in poorly differentiated cervical carcinomas, with tumor
stage II. Some of the samples were infected by strains carrying a 30bp deletion in the LMP1
gene, which indicates greater virulence. The latent pattern determined by analysis of the
expression of EBERs and viral proteins is similar to latency III or may suggest a latent state
in which EBERs are not expressed. EBV positivity was reinforced by the presence of viral

proteins in infiltrating lymphocytes and fibroblasts. Comparison of the ISH-EBER and ISH-
DNA techniques showed that the sensitivity for viral detection was greater when using the

viral genome as the target.

COMMITTEE MEMBERS:
Externa à Instituição - SILVIA HELENA BAREM RABENHORST
Interno - CLAUDIO GLEIDISTON LIMA DA SILVA
Interno - HEBERTY DI TARSO FERNANDES FACUNDO
Interno - IRI SANDRO PAMPOLHA LIMA
Interno - MARCOS ANTONIO PEREIRA DE LIMA