Detection of human papillomavirus in laryngeal squamous cell carcinoma: systematic review and meta-analysis

Background: Recent studies have reported a human papillomavirus (HPV) prevalence of 20% to 30% in laryngeal squamous cell carcinoma (LSCC), although clinical data on HPV involvement remain largely inconsistent, ascribed by some to differences in HPV detection methods or in geographic origin of the studies. Objective To perform a systematic review and formal meta-analysis of the literature reporting on HPV detection in LSCC. Methods Literature was searched from January 1964 until March 2015. The effect size was calculated as event rates (95% confidence interval [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. Potential publication bias was estimated using funnel plot symmetry. Results One hundred seventy nine studies were eligible, comprising a sample size of 7,347 LSCCs from different geographic regions. Altogether, 1,830 (25%) cases tested HPV-positive considering all methods, with effect size of 0.269 (95% CI: 0.242 to 0.297; random-effects model). In meta-analysis stratified by the 1) HPV detection technique and 2) geographic study origin, the between-study heterogeneity was significant only for geographic origin (P = .0001). In meta-regression, the HPV detection method (P = .876) or geographic origin (P = .234) were not significant study-level covariates. Some evidence for publication bias was found only for studies from North America and those using non–polymerase chain reaction methods, with a marginal effect on adjusted point estimates for both. Conclusions Variability in HPV detection rates in LSCC is explained by geographic origin of study but not by HPV detection method. However, they were not significant study-level covariates in formal meta-regression

The association of HLA-G polymorphism with oral and genital HPV infection in men

The host genetic factors that influence the natural history of human papillomavirus (HPV) infection in men are not well known. Our aim was to evaluate the role of human leukocyte antigen (HLA)-G polymorphism in oral and genital HPV infection in men. Altogether, 130 men from the Finnish Family HPV Study, with a 6-year follow-up, were included in the analyses. HLA-G alleles were tested by direct sequencing. Oral, urethral, and semen samples were collected and analyzed for 24 different HPV genotypes. Unconditional logistic regression was used to determine associations between HLA-G alleles and genotypes with HPV infection and its outcomes. Overall, eight different HLA-G alleles were identified with 15 different HLA-G genotype combinations. The most common HLA-G allele among the men was G*01:01:01 (86.2%, n = 112) followed by G*01:01:02 (36.2%, n = 47). Allele G*01:01:02 showed to be protective against any- and high-risk (HR) oral HPV (OR range of 0.20-0.24, 95% CI range of 0.06-0.85). Men having allele G*01:01:01 showed a reduced risk for incident (OR 0.30, 95% CI 0.11-0.84) and persistent (OR 0.24, 95% CI 0.08-0.69) oral infections. Allele G*01:01:03 was associated with increased risk for urethral HR-HPV infections (OR 4.94, 95% CI 1.34-18.27). Among self-reported demographic data, genotype G*01:01:01/01:01:03 was associated with an increased risk for oral warts (OR 8.00, 95% CI 1.23-51.89) and allele G*01:03:01 increased the risk of pollen and/or animal allergy (OR 13.59, 95% CI 1.57-117.25). To conclude, HLA-G polymorphism in men largely impacts the outcome of an oral HPV infection and seems to associate with self-reported allergies.Peer reviewe

Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde : results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis

Introduction: Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. Objective: To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. Methods: Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. Results: Administration of L-cysteine increased MTCA (p <.0004) and decreased gastric acetaldehyde concentrations by 68% (p <.0001). The peak L-cysteine level was 7552 +/- 2687 mu mol/L at 40 min and peak MTCA level 196 +/- 98 mu mol/L at 80 min after intake. Gastric L-cysteine and MTCA concentrations were maintained for 3 h. The AUC for MTCA was 11-fold higher than acetaldehyde, indicating gastric first-pass metabolism of ethanol. With placebo, acetaldehyde remained elevated also at low ethanol concentrations representing 'non-alcoholic' beverages and food items. Conclusions: After gastric ethanol instillation, slow-release L-cysteine eliminates acetaldehyde to form inactive MTCA, which remains in gastric juice for up to 3 h. High acetaldehyde levels indicate a marked gastric first-pass metabolism of ethanol resulting in gastric accumulation of carcinogenic acetaldehyde. Local exposure of the gastric mucosa to acetaldehyde can be mitigated by slow-release L-cysteine capsules.Peer reviewe

HPV infection and p53 and p16 expression in esophageal cancer: are they prognostic factors?

Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignant tumor. Currently, Human papillomavirus (HPV) is suggested as a potential risk factor for esophageal cancer (EC) in addition to the classic risk factors, alcohol and tobacco, but this hypothesis still remains contradictory. We sought to investigate wether HPV and well-known biomarkers (p16 and p53) and patient-related factors that may have impact on survival of ESCC. Methods: We conducted a prospective cohort study. By using multiplex PCR, we determined the prevalence of high risk HPV in ESCC, and evaluated the immunohistochemical expression of p16 and p53, molecular markers related to esophageal carcinogenesis in order to verify the potential influence of these variables in patients's survival. Survival rates were estimated using Kaplan-Meier methods. A multivariate confirmatory model was performed using Cox proportional hazards regression. Results: Twelve (13.8%) of 87 patients were HPV-DNA positive. Positive reactions of p16 and p53 were 10.7% and 68.6%, respectively. Kaplan-Meier analysis indicated that men (p = 0.025) had poor specific-cancer survival and a shorter progression-free survival (p = 0.050) as compared to women; III or IV clinical stage (p < 0.019) had poor specific-cancer survival and a shorter progression-free survival (p < 0.001) compared to I and II clinical stage; not submitted to surgery (< 0.001) and not submitted to chemoradiotherapy (p = 0.039) had a poor specific-cancer survival, as well. The multivariate analysis showed that HPV, p16 and p53 status are not predictive parameters of progression-free and specific-cancer survival. Conclusion: HPV infection and p53 and p16 expression are not prognostic factors in ESCC.CNPq Universal for providing supplies to the largest study, of which this study is a part of, entitled “The role of human papillomavirus (HPV) as the etiologic agent of esophageal cancer. A cross-sectional study, case-control and longitudinal at Barretos Cancer Hospital”; (Grant number 482666/2012–9 to ALF); INCT HPV [Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [Grant number 08/57889–1 to LLV]; Conselho Nacional de Desenvolvimento Científico e Tencnológico (CNPq) (Grant number 573799/ 2008–3 to LLV)].info:eu-repo/semantics/publishedVersio

The relation of HPV infection and expression of p53 and p16 proteins in esophageal squamous cells carcinoma

GOAL: To investigate the HPV prevalence and characterize the expression of potential molecular surrogate markers of HPV infection in esophageal squamous cell carcinoma. MATERIALS AND METHODS: The prevalence of HPV in individuals with and without esophageal cancer (EC) was determined by using multiplex PCR; p16 and p53 protein levels were assessed by immunohistochemistry (IHC). RESULTS: High-risk HPV (hr-HPV) was found in the same frequency (13.8%) in esophageal squamous cell carcinoma (ESCC) and in healthy individuals. The p53 expression was positive in 67.5% of tumor tissue, 20.0% of adjacent non-tumoral tissue and 1.8% of normal esophageal tissue. p16 was positive in 11.6% of esophageal cancer cases and 4.7% of adjacent non-tumoral tissue. p16 was undetectable among control group samples. p53 and p16 levels were not significantly associated with the HPV status. CONCLUSIONS: These results suggest that hr-HPV types are not associated with the development of ESCC and that p53 and p16 protein expression have no relationship with HPV infection in normal or cancerous esophagus.This work was supported by Conselho Nacional de Desenvolvimento Científico e Tencnológico (CNPq) [Grants number 482666/2012-9 to ALF; 573799/2008-3 to LLV]; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [Grants numbers 13/15968-0 to PRAP; 08/57889-1 to LLV]. CNPq Universal for promoting supplied to the largest study of which this study is part entitled "The role of human papillomavirus (HPV) as the etiologic agent of esophageal cancer. A cross-sectional study, case-control and longitudinal in Barretos Cancer Hospital" (Grant number 482666/2012-9 to ALF); Fundação de Amparo à Pequisa do Estado de São Paulo (FAPESP) (Grant number 13/15968-0 to PRAP); INCT HPV [Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [Grant number 08/57889-1 to LLV]; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (Grant number 573799/2008-3 to LLV)]info:eu-repo/semantics/publishedVersio

Citologia oncológica, captura de híbridos II e inspeção visual no rastreamento de lesões cervicais

Avaliar as alterações na citologia oncológica, na captura híbrida II e na inspeção visual com ácido acético (IVA) a 5% em 684 mulheres atendidas em uma unidade de saúde, e avaliar o desempenho e a concordância entre os exames. Procurar descrever as características sócio-demográficas e reprodutivas (SDR) destas mulheres e sua associação com a presença de doença. As mulheres foram submetidas à coleta de citologia, captura e IVA, e as com exame positivo foram submetidas à colposcopia com biopsia, se necessário. Foi calculado o desempenho dos testes e a associação dos fatores SDR com o diagnóstico histológico foi avaliada por intermédio do cálculo do odds ratio. Embora 198 mulheres apresentassem pelo menos um teste alterado, apenas 21 apresentaram lesão histológica. A sensibilidade dos testes foi semelhante enquanto as especificidades da IVA e da citologia foram maiores que a da captura híbrida II. Apenas a ausência de citologia esteve associada à presença de doença. O desempenho da citologia foi maior que o da IVA, que foi maior que o da captura. A ausência de citologia foi associada com doença histológica

High systemic IL-6 is associated with worse prognosis in patients with non-small cell lung cancer

Characteristic cytokine patterns have been described in different cancer patients and they are related to their diagnosis, prognosis, prediction of treatment responses and survival. A panel of cytokines was evaluated in the plasma of non-small cell lung cancer (NSCLC) patients and healthy controls to investigate their profile and relationship with clinical characteristics and overall survival. The case-controlled cross-sectional study design recruited 77 patients with confirmed diagnosis of NSCLC (cases) and 91 healthy subjects (controls) aimed to examine peripheral pro-inflammatory and anti-inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF and IFN-gamma) by Cytometry Beads Arrays (CBA Flex) in. The cytokine IL-6 showed a statistically significant difference among groups with increased expression in the case group (p < 0.001). The correlation between the cytokines expression with patient's clinical characteristics variables revealed the cytokine IL-6 was found to be associated with gender, showing higher levels in male (p = 0.036), whereas IL-17A levels were associated with TNM stage, being higher in III-IV stages (p = 0.044). We observed worse overall survival for individuals with high levels of IL-6 when compared to those with low levels of this cytokine in 6, 12 and 24 months. Further studies of IL-6 levels in independent cohort could clarify the real role of IL-6 as an independent marker of prognostic of NSCLC.Conselho Nacional de Desenvolvimento Científico e Tencnológico (CNPq) [Grant number 401775/2012-7 to ALF]; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [Grant number 2014/ 23414-8 to EMS]info:eu-repo/semantics/publishedVersio

DNA IMAGE CYTOMETRY IN PROGNOSTICATION OF COLORECTAL CANCER: PRACTICAL CONSIDERATIONS OF THE TECHNIQUE AND INTERPRETATION OF THE HISTOGRAMS

The role of DNA content as a prognostic factor in colorectal cancer (CRC) is highly controversial. Some of these controversies are due to purely technical reasons, e.g. variable practices in interpreting the DNA histograms, which is problematic particularly in advanced cases. In this report, we give a detailed account on various options how these histograms could be optimally interpreted, with the idea of establishing the potential value of DNA image cytometry in prognosis and in selection of proper treatment. Material consists of nuclei isolated from 50 ƒĘm paraffin sections from 160 patients with stage II, III or IV CRC diagnosed, treated and followed-up in our clinic. The nuclei were stained with the Feulgen stain. Nuclear DNA was measured using computer-assisted image cytometry. We applied 4 different approaches to analyse the DNA histograms: 1) appearance of the histogram (ABCDE approach), 2) range of DNA values, 3) peak evaluation, and 4) events present at high DNA values. Intra-observer reproducibility of these four histogram interpretation was 89%, 95%, 96%, and 100%, respectively. We depicted selected histograms to illustrate the four analytical approaches in cases with different stages of CRC, with variable disease outcome. In our analysis, the range of DNA values was the best prognosticator, i.e., the tumours with the widest histograms had the most ominous prognosis. These data implicate that DNA cytometry based on isolated nuclei is valuable in predicting the prognosis of CRC. Different interpretation techniques differed in their reproducibility, but the method showing the best prognostic value also had high reproducibility in our analysis