The clearance of oral high-risk human papillomavirus infection is impaired by long-term persistence of cervical human papillomavirus infection

AbstractPersistence of high-risk (HR-) human papillomavirus (HPV) infection of the uterine cervix increases the risk of cervical cancer. Oral HPV infections are among potential covariates of long-term genotype-specific persistent cervical HR-HPV infections. It is not known whether this persistence reflects inability of the host to reject HPV infections in general. A case–control setting was designed to estimate the covariates of long-term persistent cervical HR-HPV infections using multivariate generalized estimating equation (GEE) models. HPV was detected with PCR using GP05+/GP06+-primers and genotyped for 24 HPVs with a Multimetrix-kit. The cases (n = 43) included women who had genotype-specific persistent cervical HR-HPV infection for at least 24 months (24M+) and controls were women who tested repeatedly HPV-negative in their cervical samples (n = 52). These women represent a sub-cohort of the Finnish Family HPV Study. The cases differed significantly from the HPV-negative controls in several aspects: they were younger, had a longer mean time to incident oral HPV infection (40.7 versus 23.6 months), longer duration of oral HPV persistence (38.4 versus 14.1 months), and longer time to clearance of their oral HPV infection (50.0 versus 28.2 months). In multivariate GEE analysis, the second pregnancy during the follow up was the only independent predictor with significant protective effect against 24M+ persistent cervical HR-HPV infections, OR of 0.15 (95% CI 0.07–0.34). To conclude, long-term persistent cervical HR-HPV infections are associated with a prolonged clearance of oral HR-HPV infections while new pregnancy protects against persistent cervical HR-HPV infections

Solitary bronchial squamous cell papilloma – another human papillomavirus (HPV)-associated benign tumor

Aim of the study: To perform a systematic review and formal meta-analysis of the literature reporting on HPV detection in bronchial squamous cell papillomas (SCP). Material and methods: The literature was searched up to June 2012. The effect size was calculated as event rate (95% CI), with homogeneity testing using Cochran’s Q and I2 statistics. Meta-regression was used to test the impact of study-level covariates (HPV detection method, geographic origin) on effect size, and potential publication bias was estimated using funnel plot symmetry. Results: Fifteen studies were eligible, covering 89 bronchial SCPs from different geographic regions. Altogether, 38 (42.7%) cases tested HPV-positive; effect size 0.422 (95% CI: 0.311–0.542; fixed effects model), and 0.495 (95% CI: 0.316–0.675; random effects model). In meta-analysis stratified by i) HPV detection technique and ii) geographic study origin, the between-study heterogeneity was not significant for either; p = 0.348, and p = 0.792, respectively. In maximum likelihood meta-regression, HPV detection method (p = 0.150) and geographic origin of the study (p = 0.164) were not significant study-level covariates. Some evidence for publication bias was found only among in situ hybridization (ISH)-based studies and among studies from Europe, but with a negligible effect on summary effect size estimates. In sensitivity analysis, the meta-analytic results were robust to all one-by-one study removals. Conclusions: In formal meta-regression, the variability in HPV detection rates reported in bronchial SCPs is not explained by the HPV detection method or geographic origin of the study

Papillomavirus from the bench to the clinics

[Excerpt] Human papillomavirus (HPV) represents an exciting subject of study because it is currently established as an essential etiological factor of uterine cervical cancer and strongly implicated in the development of other genital cancers as well, in addition to benign genital warts. Additionally, substantial amount of new data have been elaborated linking HPV with head and neck cancer and, more tentatively, also with esophageal, breast, prostate, and lung cancers. Despite the existing controversies, the possible link of HPV infection with these nongenital carcinomas opens a new fascinating era of HPV research. [...

Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) associated with poor prognosis of head and neck carcinomas

BACKGROUND: Epstein-Barr virus (EBV) is the main cause of nasopharyngeal carcinoma (NPC), also found in other head and neck carcinomas (HNSCCs) where its role remains controversial.RESULTS: EBV was found in 80% and 21% of the samples with PCR and ISH (in cancer cells), respectively. Eight of ISH-positive samples were not NPCs. EBER-RNA detection in carcinoma cells was associated with worse prognosis, whether or not NPCs were included. HPV/EBV and HSV/HPV coinfections associated with a shorter survival. LMP-1 expression, positive in 51% of samples did not correlate with the disease outcome.MATERIALS AND METHODS: We analyzed EBV in 73 HNSCC samples with a known HPV and HSV-1 status, using in situ hybridization (ISH) and immunohistochemistry (IHC) for EBV-early transcripts (EBER) and LMP-1 protein, respectively. EBV-DNA was detected with a Luminex-based method. The results were correlated with HPV-status and disease outcome.CONCLUSIONS: EBV is transcriptionally active in NPC cells but also in a subgroup of other HNSCCs.</p

The Potential Value of EGFR and P53 Immunostaining in Tumors of the Urinary Bladder

The expression of EGFR and p53 has not been adequately studied as a prognostic tool in urinary bladder tumors. We analyzed 74 bladder cancer samples from Egypt for EGFR and p53 expression using immunohistochemistry. The tumors were of different histological types, grades and clinical stages, and with established lymph node status. Almost 61% of the tumors showed positive membranous EGFR expression and 74.3% had positive nuclear staining of p53. Analysis of correlation of the IHC staining with clinical variables showed a significant correlation only between EGFR expression and histological type (p=0.002, ANOVA), in that the expression was higher in squamous cell carcinomas than in other histological types. There were no significant correlations between p53 or EGFR with the other clinicopathological variables, including age, sex, staging, grading, and lymph node status. Further studies are needed to determine if EGFR and p53 might be used as prognostic tools in bladder cancer

The Potential Value of EGFR and P53 Immunostaining in Tumors of the Urinary Bladder

The expression of EGFR and p53 has not been adequately studied as a prognostic tool in urinary bladder tumors. We analyzed 74 bladder cancer samples from Egypt for EGFR and p53 expression using immunohistochemistry. The tumors were of different histological types, grades and clinical stages, and with established lymph node status. Almost 61% of the tumors showed positive membranous EGFR expression and 74.3% had positive nuclear staining of p53. Analysis of correlation of the IHC staining with clinical variables showed a significant correlation only between EGFR expression and histological type (p=0.002, ANOVA), in that the expression was higher in squamous cell carcinomas than in other histological types. There were no significant correlations between p53 or EGFR with the other clinicopathological variables, including age, sex, staging, grading, and lymph node status. Further studies are needed to determine if EGFR and p53 might be used as prognostic tools in bladder cancer.Key words: Bladder cancer, p53, EGFR, Immunohistochemistry, Clinical data

Human polyomavirus BKPyV and JCPyV serostatus has no impact on women´s human papillomavirus infection outcome

IntroductionPolyomaviruses have both structural and functional similarities with papillomaviruses. Accordingly, their role in human papillomavirus (HPV) associated malignancies has been studied with conflicting results. Our goal was to disclose any association between BK (BKPyV) and/or JC (JCPyV) polyomavirus serology and HPV data derived from Finnish women (327) in a 6-year prospective follow-up.MethodsGlutathione S-transferase fusion-protein-capture (ELISA) in combination with fluorescent bead technology was used to analyze antibodies to BKPyV and JCPyV. In the longitudinal setting, BKPyV or JCPyV serostatus was related to i) oral- and ii) genital low (LR)- and high risk (HR) HPV DNA detection, iii) HPV16 persistence at both these sites, iv) results of the Pap (Papanicolaou) smear taken at baseline, and v) development of incident CIN (cervical intraepithelial neoplasia) during the follow-up.ResultsBeing BKPyV or JCPyV seropositive was not significantly associated with HPV seropositivity to either LR- or HR-genotypes, genital- or oral HPV DNA positivity, persistence of genital- or oral HPV16 infection, grade of Pap smear, or development of incident CIN.DiscussionThus, the present study could not provide any confirmation to the concept that co-infections by HPyV and HPV have interactions that impact on the clinical manifestations or outcomes of HPV infections either in the genital tract or in the oral mucosa