Banca de DEFESA: JULIA GRAZIELE ALVES MARELLI

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : JULIA GRAZIELE ALVES MARELLI
DATE: 26/09/2024
TIME: 14:00
LOCAL: Sala de Videoconferência - Faculdade de Medicina - UFCA
TITLE:

ROLE OF HPV, EBV, AND CMV IN CERVICAL CARCINOMA: Association with E- Cadherin Oncoprotein.

KEY WORDS:

EBV; CMV; cervical carcinoma; E-cadherin; LMP1.

PAGES: 135
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

Cervical cancer is the fourth most common neoplasm among women worldwide and the third most frequent type in Brazil, with a mortality rate of 5.74 per 100,000 women in Ceará alone. The main risk factor is HPV infection; however, studies suggest a potential role of Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) in oncogenesis. Objectives: This study investigated the association of EBV and CMV with cervical carcinoma and premalignant lesions, exploring their interaction with HPV and the human oncoprotein E-cadherin. Methodology: A total of 79 cases of cervical carcinoma and 51 outpatient biopsies, including premalignant and non- malignant lesions, were analyzed. Samples underwent PCR for the detection of HPV, CMV, and EBV, as well as HPV16 and 18 genotyping. qPCR was used to quantify EBV, in situ hybridization (ISH) for EBERs and EBV DNA, and immunohistochemistry for LMP1 and E- cadherin. The 30bp deletion in the viral LMP1 gene, EBV sequencing for target confirmation, and HPV16 integration were also assessed. Results: HPV was detected in 94.9% of carcinomas and 78.4% of biopsies. HPV16 integration was observed in 44.4% of outpatient samples and 89.4% of carcinomas, indicating a strong association with tumor progression (OR=10.6; P<0.01). EBV was identified by PCR in 30.4% of carcinomas (OR=5.1; P<0.01), with a higher viral load in squamous cell carcinomas (P=0.05) and moderately differentiated tumors (P=0.03). The 30bp deletion in the EBV LMP1 gene, present in 19% of carcinomas, was associated with virulence and HPV16 integration. CMV was found in 10.1% of carcinomas, particularly in adenocarcinomas. E-cadherin showed positive membrane expression in 55.4% of squamous cell carcinomas. Additionally, membrane E-cadherin expression increased the likelihood of HPV16 integration ninefold (OR=9.0). An inverse correlation (Rho=-0.397; P=0.041) between the membrane E-cadherin Labelling Index (LI) and EBV viral load was also observed, highlighting the interaction between E-cadherin expression and viral load in tumor progression. Conclusion: This study reinforces the association between EBV and cervical carcinoma, emphasizing the importance of EBV, alongside HPV, in disease progression. The 30bp deletion in the LMP1 gene and HPV16 integration into the host genome are indicative of greater tumor aggressiveness, while the presence of CMV requires further investigation. Regarding E-cadherin expression, the observed inverse correlation suggests that higher EBV viral loads are associated with lower E-cadherin expression levels. These findings underscore the relevance of multiple viral factors in the development of cervical cancer and suggest a possible collaboration between EBV and HPV, highlighting the need for further studies that could ultimately reshape early diagnosis, prevention, and treatment strategies.

COMMITTEE MEMBERS:
Externa à Instituição - VALESKA PORTELA LIMA
Interno - HEBERTY DI TARSO FERNANDES FACUNDO
Externo à Instituição - HENRIQUE DOUGLAS MELO COUTINHO - URCA
Presidente - MARCOS ANTONIO PEREIRA DE LIMA