Name: LAYS PAULA BONDI VOLPINI

Publication date: 18/03/2021
Advisor:

Name	Role
LILIANA CRUZ SPANO	Advisor *

Examining board:

Name	Role
ANA PAULA FERREIRA NUNES	Internal Examiner *
ANGELICA ESPINOSA BARBOSA MIRANDA	Co advisor *
KÊNIA VALÉRIA DOS SANTOS	Internal Examiner *
LILIANA CRUZ SPANO	Advisor *
SANDRA LÚCIA VENTORIN VON ZEIDLER	External Examiner *

Summary: Infection with high-risk genotypes of human papillomavirus (HR-HPV) is the main risk factor for the development of cervical (CC) and anal (CA) cancer. Some populations are more vulnerable to the development of these cancers, either due to immunosuppression, as in HIV-positive individuals, or due to limited access to health services, as is the case of quilombola women. The use of biomarkers, such as viral load and expression of viral oncogenes, would be useful to guide future screening algorithms in these populations. This study aimed to determine the HPV genotypes in populations of vulnerable women (HIV-positive and quilombola) and to investigate whether viral load and quantification of HR-HPV E7 oncogene (E7 mRNA) transcripts are related to cervical and anal lesions of HIV-positive and negative individuals. Viral DNA was screened by PCR, the genotype determined by Reverse Line Blot (RLB) and Restriction Fragment Length Polymorphism (RFLP), and the HPV16 variants were determined by genetic sequencing. Viral load and E7 mRNA were obtained by real-time PCR. In quilombola women, the frequency of HPV was 11.4% and associated with cytological abnormalities (p <0.001). HR-HPV infection occurred in 64.5% and, the most frequent types were HPV52> 58, 59. Viral load was higher in lesions than in normal cytology cases (p= 0.04). In HIV-positive women, HPV16, 52, and 31 were the most frequent and, the European HPV16 variant was the most prevalent. There was an increase of viral load median from normal cytology to lesion in HIV-positive and negative individuals (p= 0.01). This increase was significant in HPV16-positive cervical samples from HIV-negative women (p <0.001) and in HPV31-positive cervical and anal samples (p = 0.04 and p = 0.02, respectively) in HIV-positive individuals. In the analysis of mRNA E7, there was an increase in the median from normal to injury (p= 0.02) and a moderate and positive correlation between increased viral load and detection of mRNA (r= 0.61; p <0.001). This study demonstrated that the most frequent genotypes in vulnerable populations are those included in the nonavalent vaccine and the highest viral load and mRNA present in cases of cervical and anal lesions, indicating the benefit of this vaccine and these biomarkers for screening for cancer precursor lesions in these populations

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