Case-Control Study on the Role of Epstein-Barr Virus (EBV) and Human Papillomavirus (HPV) in
Cervical Carcinogenesis
Human Papillomavirus; Epstein-Barr Virus Infections; Uterine Cervical Neoplasms; Odds Ratio.
Cervical cancer remains one of the major public health problems worldwide, with high incidence and
mortality rates, especially in developing countries. Persistent infection with Human Papillomavirus
(HPV), particularly high-risk types, is the main etiological factor for cervical carcinogenesis. However,
the literature points to the possible involvement of other oncogenic microorganisms, such as Epstein-
Barr Virus (EBV), acting as a cofactor in tumor progression. This study investigated the presence of
Epstein-Barr Virus and Human Papillomavirus in non-dysplastic tissues and pre-neoplastic cervical
lesions, through molecular analysis and viral genotyping, in comparison with cervical carcinoma cases.
This is an analytical, non-interventional, case-control study including 181 cervical samples, distributed
into 79 carcinomas, 67 squamous intraepithelial lesions, and 35 controls with non-dysplastic tissues.
The samples were obtained from healthcare services linked to UFCA and from ICC, stored at -86°C,
and subjected to DNA extraction. Viral detection was performed using PCR, with specific genotyping
for HPV16/18, analysis of HPV16 integration, and evaluation of the 30bp deletion in the EBV LMP1
gene. Statistical analysis included association tests and binary logistic regression (GLM), with
calculation of Odds Ratios (OR) and 95% confidence intervals (95% CI). Viral detection revealed
positivity for HPV-16 (48.1%) in carcinomas, followed by HPV-18 (7.6%), while EBV was detected in
30.4% of cases. In intraepithelial lesions, HPV-16 and EBV were positive in 16.4%, and HPV-18 in
6%. In non-dysplastic tissues, detection rates were 5.7% for HPV-16, 14.3% for HPV-18, and 22.9%
for EBV. Integration of HPV-16 into the host genome was observed in 89.5% of carcinomas and 72.7%
of intraepithelial lesions, representing an important marker of disease progression. The mean age was
significantly higher in women with carcinoma (47.2 years), and those aged 50 years or older had a 13.8-
fold greater risk of progression (p=0.006). Smoking was also associated with an increased likelihood of
carcinoma (OR=2.84; p=0.020). Logistic regression confirmed HPV-16 and positivity in Nested-PCR-
HPV as the main predictors of carcinoma. In intraepithelial lesions, no significant predictors of
progression were identified when compared with controls. These findings reinforce the central role of
HPV, particularly genotype 16 and its integration, in cervical carcinogenesis, while EBV, although
detected, showed no statistical significance, possibly due to methodological limitations of PCR and
sample size. The results are consistent with international literature, highlighting advanced age,
smoking, and viral integration as additional risk factors. Thus, this study contributes to understanding
the interaction between viral and clinical factors in cervical carcinogenesis, emphasizing the need for
early screening, control of risk factors, and further investigations into the role of EBV in HPV
coinfection. The study demonstrated the high prevalence of HPV, especially genotype 16, whose
integration into the host genome is related to tumor progression. Age ≥50 years and smoking were
significant risk factors. Although EBV was detected, no association with lesion progression was found,
suggesting a possible modulatory role that has not yet been confirmed. The results highlight the
importance of combining sensitive viral detection techniques for screening, diagnosis, and follow-up, in
addition to indicating the need for multicenter studies on HPV/EBV coinfection.