Prognostic Evaluation of DNA Index in HIV-HPV Co-Infected Women Cervical Samples Attending in Reference Centers for HIV-AIDS in Recife

Martins, Albert Eduardo Silva; Lucena‐Silva, Norma; Garcia, Renan Gomes; Welkovic, Stefan; Barbosa, Aureliana; Menezes, Maria Luiza Bezerra; Tenório, Terezinha; Maruza, Magda; Ximenes, Ricardo A. A.

doi:10.1371/journal.pone.0104801

Cited by 4 publications

(11 citation statements)

References 31 publications

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Section: Resultsmentioning

confidence: 99%

“…We recently reported a lack of association between aneuploidy in cervical cells and HIV + /HPV + co-infection ( p = 0.22), low-risk ( p = 0.43) or high-risk HPV ( p = 0.17), and cytological alteration ( p = 0.35) in the HIV-infected women cohort [ 28 ]. However, aneuploidy was associated with histological lesion ( p = 0.03) [ 28 ]. Considering that aneuploidy is a phenomenon associated with cervical cell transformation, and HLA-G is an immune checkpoint protein with inhibitory effect on several immune cells, we hypothesized that women harboring HLA-G 3’UTR alleles associated with high HLA-G expression may also have higher risk to develop aneuploidy.…”

Section: Resultsmentioning

confidence: 99%

“…All women answered a questionnaire for clinical and epidemiological assessment, before undergoing colposcopy and cytological examination. Colposcopy was performed according to the criteria of the International Nomenclature of Colposcopy Aspects of Rome [ 27 – 28 ]. Endocervical samples collected using cytobrush were used for cytological analysis, detection of HPV co-infection and immunogenetic studies.…”

Section: Methodsmentioning

confidence: 99%

“…DNA fluorescence was measured by flow cytometry (laser excitation at 488 nm and emission above 600 nm), and DNA index was estimated through by comparison the ratio of the DNA content of cells analyzed with labeled blood diploid cells using the ModFitLT V3.0 software (Verity Software House Inc., Topsham, USA). The presence of two peaks on a histogram with a DNA index greater than 1.16 (hyperploidy) or less than 1.00 (hypoploidy), each with more than 10% of the cell population analyzed in the area corresponding to G0–G1 of the cell cycle in the sample, was considered to be aneuploidy [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…Despite the high frequency of HPV infection, we observed a low occurrence of cervical lesions in the HIV + women, which was attributed to the high adherence to antiretroviral therapy [ 27 ]. In addition, we observed an association between cellular intraepithelial neoplasia and the presence of aneuploid cells, which causes genomic instability in cervical cells of HIV + /HPV + women [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Variation sites at the HLA-G 3’ untranslated region confer differential susceptibility to HIV/HPV co-infection and aneuploidy in cervical cell

et al. 2018

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Post-transcriptional regulatory elements associated with transcript degradation or transcript instability have been described at the 3’ untranslated region (3’UTR) of the HLA-G gene. Considering that HPV infection and aneuploidy, which causes gene instability, are associated with cervical cell malignancy, as well as the fact that HIV infection and HLA-G may modulate the immune response, the present study aimed to compare the frequencies of HLA-G 3′UTR polymorphic sites (14-base pair insertion/deletion, +3142C/G, and +3187A/G) between 226 HIV+ women co-infected (n = 82) or not with HPV (n = 144) and 138 healthy women. We also evaluated the relationship between those HLA-G 3’UTR variants and aneuploidy in cervical cells. HPV types and HLA-G polymorphisms were determined by PCR and sequencing of cervical samples DNA. Aneuploidy in cervical cell was measured by flow cytometry. The HLA-G 3’UTR 14-bp ins/del was not associated with either HIV nor HIV/HPV co-infection. The +3142G allele (p = 0.049) and +3142GG genotype (p = 0.047) were overrepresented in all HIV-infected women. On the other hand, the +3187G allele (p = 0.028) and the +3187GG genotype (p = 0.026) predominated among healthy women. The +3142G (p = 0.023) and +3187A (p = 0.003) alleles were associated with predisposition to HIV infection, irrespective of the presence or not of HIV/HPV co-infection. The diplotype formed by the combination of the +3142CX (CC or CG) and +3187AA genotype conferred the highest risk for aneuploidy in cervical cell induced by HPV. The HLA-G 3’UTR +3142 and +3187 variants conferred distinct susceptibility to HIV infection and aneuploidy.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Variation sites at the HLA-G 3’ untranslated region confer differential susceptibility to HIV/HPV co-infection and aneuploidy in cervical cell

et al. 2018

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Hierarchical evaluation of histology and p16-labeling can improve the risk assessment on cervical intraepithelial neoplasia progression

Medeiros

Gomes

Paiva

et al. 2022

Experimental and Molecular Pathology

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Increased PD-1 Level in Severe Cervical Injury Is Associated With the Rare Programmed Cell Death 1 (PDCD1) rs36084323 A Allele in a Dominant Model

Silva

Medeiros

Silva

et al. 2021

Front. Cell. Infect. Microbiol.

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The high-risk oncogenic human papillomavirus (HPV) has developed mechanisms for evasion of the immune system, favoring the persistence of the infection. The chronic inflammation further contributes to the progression of tissue injury to cervical cancer. The programmed cell death protein (PD-1) after contacting with its ligands (PD-L1 and PD-L2) exerts an inhibitory effect on the cellular immune response, maintaining the balance between activation, tolerance, and immune cell-dependent lesion. We evaluated 295 patients exhibiting or not HPV infection, stratified according to the location (injured and adjacent non-injured areas) and severity of the lesion (benign, pre-malignant lesions). Additionally, we investigated the role of the promoter region PDCD1 -606G>A polymorphism (rs36084323) on the studied variables. PD-1 and PDCD1 expression were evaluated by immunohistochemistry and qPCR, respectively, and the PDCD1 polymorphism was evaluated by nucleotide sequencing. Irrespective of the severity of the lesion, PD-1 levels were increased compared to adjacent uninjured areas. Additionally, in cervical intraepithelial neoplasia (CIN) I, the presence of HPV was associated with increased (P = 0.0649), whereas in CIN III was associated with decreased (P = 0.0148) PD-1 levels, compared to the uninjured area in absence of HPV infection. The PDCD1 -606A allele was rare in our population (8.7%) and was not associated with the risk for development of HPV infection, cytological and histological features, and aneuploidy. In contrast, irrespective of the severity of the lesion, patients exhibiting the mutant PDCD1 -606A allele at single or double doses exhibited increased protein and gene expression when compared to the PDCD1 -606GG wild type genotype. Besides, the presence of HPV was associated with the decrease in PDCD1 expression and PD-1 levels in carriers of the -606 A allele presenting severe lesions, suggesting that other mediators induced during the HPV infection progression may play an additional role. This study showed that increased PD-1 levels are influenced by the -606G>A nucleotide variation, particularly in low-grade lesions, in which the A allele favors increased PDCD1 expression, contributing to HPV immune system evasion, and in the high-grade lesion, by decreasing tissue PD-1 levels.

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Prognostic Evaluation of DNA Index in HIV-HPV Co-Infected Women Cervical Samples Attending in Reference Centers for HIV-AIDS in Recife

Cited by 4 publications

References 31 publications

Variation sites at the HLA-G 3’ untranslated region confer differential susceptibility to HIV/HPV co-infection and aneuploidy in cervical cell

Variation sites at the HLA-G 3’ untranslated region confer differential susceptibility to HIV/HPV co-infection and aneuploidy in cervical cell

Hierarchical evaluation of histology and p16-labeling can improve the risk assessment on cervical intraepithelial neoplasia progression

Increased PD-1 Level in Severe Cervical Injury Is Associated With the Rare Programmed Cell Death 1 (PDCD1) rs36084323 A Allele in a Dominant Model

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