Banca de QUALIFICAÇÃO: JULIA GRAZIELE ALVES MARELLI

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : JULIA GRAZIELE ALVES MARELLI
DATE: 21/08/2024
TIME: 14:00
LOCAL: Sala de Videoconferência da Faculdade de Medicina - UFCA (campus Barbalha)
TITLE:

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

KEY WORDS:

EBV; CMV; cervical carcinoma; oncoproteins; LMP1.

PAGES: 114
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

Cervical cancer is the fourth most common neoplasm among women and accounts for 6.5% of
female deaths worldwide. In Brazil, it is the third most frequent type, and in Ceará, it has a
mortality rate of 5.74 per 100,000 women. The main risk factor is Human Papillomavirus (HPV),
but Epstein-Barr virus (EBV) may also be involved in oncogenesis. Cytomegalovirus (CMV),
which belongs to the same family as EBV, has also been studied for its potential pathological
associations. The aim of this study was to examine the association of EBV and CMV with
cervical carcinoma and precancerous lesions, as well as to explore potential interactions with
HPV and oncoproteins involved in disease progression. Methodology: A total of 79 cases of
cervical carcinoma and 51 outpatient biopsies were analyzed, including 39 premalignant lesions
and 12 non-malignant lesions (polyps and cervicitis). The samples were subjected to PCR for the
detection of HPV, CMV, and EBV; qPCR for EBV quantification; in situ hybridization (ISH) to
detect EBV RNAs (EBERs) and DNA; and immunohistochemistry for LMP1 and E-cadherin
proteins. Additionally, the presence of a 30bp deletion in the LMP1 gene of EBV was assessed,
and EBV-positive cases were sequenced to evaluate the genotype. PCR was also performed for
HPV16 and 18 genotyping, as well as for the assessment of HPV16 integration into the host
genome. Results: HPV was detected in 94.9% of carcinomas and 78.4% of biopsies (OR=5.1;
P<0.01), with HPV16 present in 50.6% and 22.5%, respectively (OR=3.5; P<0.01). HPV16
integration was observed in 44.4% of outpatient samples and 89.4% of carcinomas (OR=10.6;
P<0.01), indicating a strong association with tumor progression. EBV was detected by PCR in
30.4% of carcinomas and 7.8% of biopsies (OR=5.1; P<0.01). qPCR confirmation reinforced the
presence of EBV, and viral load was higher in squamous cell carcinomas (P=0.05) and
moderately differentiated tumors (P=0.03). The 30bp deletion in the LMP1 gene of EBV was
identified in 19% of carcinomas (OR=6.0; P=0.222), suggesting that this deletion may be a
relevant marker of virulence. This deletion also showed an association with HPV16 integration
(OR=6.4; P=0.289), indicating that cases with this deletion are more likely to have HPV16 

integrated into the genome. Cytomegalovirus (CMV) was found in 10.1% of cervical carcinomas,
with higher prevalence in adenocarcinomas (17.4% [OR=2.3; P=0.47]). Although not statistically
significant, the findings suggest that CMV may influence certain subtypes of cervical carcinoma.
In situ hybridization for EBERs identified EBV in 11.4% of carcinomas, while ISH-DNA showed
41.8% positivity, both with staining in malignant cells. Immunohistochemistry for LMP1 revealed
17.7% positivity, confirming its role in EBV-associated oncogenesis. Staining in infiltrated
lymphocytes was also observed through all three histological methods. Conclusion: The study
confirms the significant association between EBV and cervical carcinoma, highlighting 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 in adenocarcinomas suggests a possible clinical relevance that warrants
further investigation.

COMMITTEE MEMBERS:
Interno - IRI SANDRO PAMPOLHA LIMA
Interna - JACQUELINE COSMO ANDRADE PINHEIRO
Presidente - MARCOS ANTONIO PEREIRA DE LIMA