Luisa L. Villa

Correlation between cervical HPV DNA detection and HPV16 seroreactivity measured with L1-only and L1+L2 viral capsid antigens

Introduction.Persistent human papillomavirus (HPV) type 16 infection is the main causal agent of cervical cancer. Most HPV infections clear spontaneously within 1–2 years. Although not all infected women develop detectable HPV antibodies, about 60–70 % seroconvert and retain their antibodies at low levels.Aim.We investigated if cervical HPV16 DNA positivity was associated with HPV16 seroreactivity measured with two different antigen formulations. We assessed if associations were influenced by co-infection with other HPV types and HPV16 viral load.Methodology.We used baseline data for women participating in the Ludwig–McGill cohort, a longitudinal investigation of the natural history of HPV infection and cervical neoplasia. The study enrolled 2462 Brazilian women from 1993 to 1997 (pre-vaccination). ELISA assays were based on L1-only or L1+L2 virus-like particles (VLPs). Seroreactivity was expressed as normalized absorbance ratios. HPV genotyping and viral load were evaluated by PCR protocols. Pearson’srwas used to measure correlations between interval-scaled variables. Serological accuracy in HPV16 DNA detection was assessed using receiver operating characteristic (ROC) curves. We analysed the association between HPV DNA positivity and HPV16 seroreactivity by linear regression.Results.Correlations between L1+L2 and L1-only VLPs for detection of HPV16 were poor (r=0.43 and 0.44 for dilutions 1 : 10 and 1 : 50, respectively). The protocol with the best accuracy was L1+L2 VLPs at serum dilution 1 : 10 (ROC area=0.73, 95 % CI: 0.65–0.85). HPV16 DNA positivity was correlated with HPV16 seroreactivity and was not influenced by co-infection or viral load. To a lesser degree, HPV16 seroreactivity was correlated with infection by other Alpha-9 papillomavirus species.Conclusion.HPV16 DNA positivity and HPV16 seroreactivity are strongly correlated. L1+L2 VLPs perform better than L1-only VLPs for detecting IgG antibodies to HPV16 in women infected with HPV16 or other Alpha-9 HPV species. This study advances our understanding of humoral immune responses against HPV16 by providing insights about the influence of VLP antigen composition to measure humoral immune response against naturally acquired HPV infection.

Is there a higher frequency of anal dysplasia and infection by human papillomavirus in Crohn's disease patients?

The aim of this study was to compare the frequency of dysplasia and human papillomavirus (HPV) infection in the anal canal of patients with Crohn's disease (CD) with a control group and assess whether there is a correlation between use of immunosuppressants and anal manifestation of CD. Patients with CD and control individuals were submitted to anal cytology and material collection for polymerase chain reaction (PCR). The cytology was classified as normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or high-grade (HSIL). PCR was considered positive or negative according to virus presence or absence. A total of 117 patients were included (54 in the control group and 63 in the CD group, being 32 without and 31 with immunosuppressants). ASCUS and LSIL were found in 25.9 and 22.2% of control patients and 28.6 and 39.7% of CD patients. HPV was identified in 14.8% of the control group and 27% of the CD group. In CD patients, HPV was found in 37.5 and 16.1% of those without and with immunosuppressants, respectively. Patients with perianal involvement had 15.6% of PCR positivity. There was no statistical difference in dysplasia and infection by HPV between the groups. Use of immunosuppressants did not influence the result, but anal manifestation was inversely proportional to viral detection.

CD40/CD40L expression and its prognostic value in cervical cancer

CD40, a member of the tumor necrosis factor receptor (TNFR) family, is known to be involved in immune system regulation, acting as a costimulatory molecule, and in antitumor responses against cancer cells. It is a protein that is expressed in different types of cells, including immune cells and cancer cells (e.g., cervical cancer, breast cancer, melanoma). In this study, we investigated CD40/CD40L transcriptional and protein levels in cervical cancer cell lines and tumors. Higher CD40 expression was observed in cervical cancer cell lines derived from squamous cell carcinomas than from adenocarcinomas. Search of CD40/CD40L expression in cervical cancer tissues in public data sets revealed that about 83% of squamous cell carcinomas express CD40 compared to other cervical tumor subtypes. Moreover, expression of CD40 and CD40L in squamous cervical carcinomas is associated with better overall survival. Therefore, these proteins could be explored as prognostic markers in cervical cancers.

Self-sampling for HPV genotyping: a study of vaginal and urine collection in Brazilian women with high-grade lesions

In Brazil - a country of continental dimensions with marked socioeconomic disparities - the use of self-collected samples and first-void urine for cervical cancer screening may be particularly valuable. This study aimed to assess the acceptability of two self-sampling approaches - first-void urine collection and vaginal self-sampling - among women diagnosed with high-grade cervical lesions (CIN2+) referred to a tertiary care center. Additionally, the study evaluated the concordance of high-risk HPV (hrHPV) test results obtained from self-collected samples compared to those collected by a healthcare professional. This cross-sectional study included 100 women. Participants completed a structured questionnaire on clinical history, demographics, gynecological and obstetric background. Following an instructional video, they performed self-collection of urine and vaginal samples. All participants then underwent colposcopic examination for lesion assessment and therapeutic planning. HPV DNA testing was conducted, and agreement analysis was performed between sample types. Both urine and vaginal self-collection methods were reported as easy and comfortable. Instructions were considered easy or very easy by nearly all participants for all collection methods. Clinician-collected sampling was associated with higher embarrassment and discomfort. Agreement analysis showed excellent concordance for HPV 16 and other high-risk HPV types between self-collected, urine, and clinician-collected samples, with all comparisons reaching statistical significance. Urine and vaginal self-collection are feasible, acceptable, and reliable methods. Urine sampling was the preferred method in the present study. High concordance with clinician-collected samples confirms their clinical utility, and the positive response to instructional videos highlights the importance of educational support.