Francesca Taverna

Testing of human papillomavirus in lung cancer and non-tumor lung tissue.

BackgroundRisk factors for lung cancer, such as cigarette smoking, environmental pollution, asbestos, and genetic determinants, are well-known, whereas involvement of the human papillomavirus (HPV) is still unclear.MethodsWe examined a series of 100 lung cancer patients from Italy and the UK for the presence of HPV DNA in both lung tumor specimens and adjacent non-tumoral specimens from the same patients. Thirty-five of the most clinically relevant HPV types were assayed using PCR amplification of the highly conserved L1 region of the viral genome followed by hybridization with specific probes.ResultsNo HPV was detected in tumor specimens nor in normal lung tissue of any patient.ConclusionsThese data indicate that, in this Western series, HPV is not associated with the risk of lung cancer. Our findings will help refine estimates of lung cancer risk in patients affected by a common viral infection involved in other types of human cancer.

The association of pre-treatment HPV subtypes with recurrence of VIN

OBJECTIVE To assess whether pre-treatment HPV types are associated with recurrence of high-grade vulvar intraepithelial neoplasia (VIN2+). STUDY DESIGN Data of consecutive patients with pretreatment HPV DNA test undergoing treatment for VIN2+ were retrospectively collected. Risk factors promoting the risk of VIN2+ persistence and recurrence were analyzed using Kaplan-Meier and Cox hazard proportional models. RESULTS 64 patients had pretreatment vulvar-vaginal HPV DNA test. Two were excluded due to the presence of synchronous vulvar cancer, thus leaving 62 patients for the final analysis. HPV16, HPV18, HPV31 and HPV33 were the most common HPV genotype detected, occurring in 15 (24.2%), 4 (6.5%), 8 (12.9%) and 5 (8.0%) patients, respectively. HPV was not detected in 19 (30.6%) patients. During a mean (SD) follow up of 56.7 (±26.7) months, 10 (16.1%) patients had VIN2+ persistence/recurrence. Mean (SD) lesion-free interval was 51.7 (±31.4) months. Via multivariate analysis, pretreatment infection from HPV31 (HR:46.7(95%CI:4.21,518.4); p=0.02) and HPV33 (HR:77.0(95%CI:6.73,881.9); p<0.001) correlated with an increased risk of VIN2+ persistence/recurrence. Additionally, we observed that patients undergoing surgical excision followed by LASER ablation experienced a trend towards lower recurrence rate than patients undergoing other surgical or medical treatments (HR:0.20(95%CI:0.03,1.09); p=0.05). Two (3.2%) patients developed progression to vulvar cancer. CONCLUSIONS Owing to the inherent biases of the retrospective study design and the small sample size, our data have to be corroborated by larger and prospective studies. HPV31 and HPV33 have a potential role in predicting VIN2+ persistence/recurrence. These findings will be paramount, owing to the implementation of new immunization programs.

Human papillomavirus (HPV) persistence and HPV 31 predict the risk of recurrence in high-grade vaginal intraepithelial neoplasia

OBJECTIVE High-grade vaginal intraepithelial neoplasia (vaginal HSIL) represents an uncommon entity. Here, we sought to identify predictors for recurrence and risk factor for developing genital cancers after primary treatment for vaginal HSIL. METHODS Data of consecutive 5104 women who had human papillomavirus (HPV) DNA test were searched for identify women with histological confirmed vaginal HSIL. Disease-free interval and the risk of developing HPV-related gynecological cancers were assessed using Kaplan-Meier and Cox proportional hazard models. RESULTS Overall, 77 patients were included. After a mean (SD) follow-up of 69.3 (33.0) months, 11 (14%) and 4 (5%) patients experienced vaginal HSIL recurrence and the occurrence of HPV-related gynecological cancers, respectively. Via multivariate analysis factors predicting for vaginal HSIL recurrence were infection from HPV31 at diagnosis (HR: 5.0 (95%CI:1.17, 21.3); p=0.03) and persistence of HPV infection after treatment (HR: 7.0 (95%CI:1.54, 31.6); p=0.01). Additionally, patients who had LASER ablation experienced a trend toward a lower risk of recurrence in comparison to medical treatment (HR: 0.20 (95%CI:0.03, 1.09); p=0.06). Considering the occurrence of HPV-related gynecological cancers, we observed that no factors independently correlated with this risk; while, a trend towards higher risk was observed for women with HIV infection (HR:16.4 (95%CI:0.90, 300.1); p=0.06) and persistence of HPV infection (HR: 13.3 (95%CI:0.76, 230.2); p=0.07). CONCLUSIONS Patients affected by vaginal HSIL experienced a relatively high risk of recurrence. Persistence of HPV after treatment and pretreatment HPV-31 infection predicts for high-grade vaginal intraepithelial neoplasia recurrence. Further investigations are warranted in order to corroborate our data.

Baseline C-reactive protein level predicts survival of early-stage lung cancer: evidence from a systematic review and meta-analysis.

Purpose The prognostic impact of baseline C-reactive protein (CRP) in non-small-cell lung cancer (NSCLC) is debated. To evaluate this issue, we performed a systematic review and meta-analysis to explore the role of CRP value in predicting early-stage NSCLC survival. Methods Ten articles on early-stage NSCLC were eligible and included in our study. We performed a random-effects meta-analysis and assessed heterogeneity and publication bias. We pooled hazard ratio (HR) estimates and their 95% confidence intervals (CIs) on mortality for the comparison between the study-specific highest category of CRP level versus the lowest one. Results In overall analysis, elevated pretreatment CRP values were significantly associated with poor overall survival (HR 1.60, 95% CI 1.30-1.97, p<0.001, I2 = 71.9%). Similar results were observed across considered strata. However, higher mortality risk was reported in studies in which CRP was combined with other factors (HR 1.96, 95% CI 1.58-2.45) and in those using a cutoff value of 3 mg/L (HR 1.89, 95% CI 1.52-2.35). Conclusions Based on our analysis, baseline high CRP level is significantly associated with poor prognosis in early-stage NSCLC. Further prospective controlled studies are needed to confirm these data.

Retrospective study of the influence of HPV persistence on outcomes among women with high‐risk HPV infections and negative cytology

To evaluate the outcomes of women diagnosed with high‐risk HPV without cytology evidence of cervical dysplasia.

C-reactive protein level predicts mortality in COPD: a systematic review and meta-analysis

The prognostic role of baseline C-reactive protein (CRP) in chronic obstructive pulmonary disease (COPD) is controversial. In order to clarify this issue, we performed a systematic review and meta-analysis to assess the predictive effect of baseline CRP level in COPD patients. 15 eligible articles focusing on late mortality in COPD were included in our study. We performed a random-effects meta-analysis, and assessed heterogeneity and publication bias. We pooled hazard ratio (HR) estimates and their 95% confidence intervals on mortality for the comparison between the study-specific highest category of CRP level versus the lowest category. In overall analysis, elevated baseline CRP levels were significantly associated with higher mortality (HR 1.53, 95% CI 1.32–1.77, I2=68.7%, p<0.001). Similar results were observed across subgroups. However, higher mortality risk was reported in studies using a cut-off value of 3 mg·L−1 (HR 1.61, 95% CI 1.12–2.30) and in those enrolling an Asiatic population (HR 3.51, 95% CI 1.69–7.31). Our analysis indicates that baseline high CRP level is significantly associated with higher late mortality in patients with COPD. Further prospective controlled studies are needed to confirm these data. Baseline high CRP level is significantly associated with higher mortality in COPD patients http://ow.ly/iWKb305aYvL

Inflammatory status and lung function predict mortality in lung cancer screening participants

Low-dose computed tomography (LDCT) screening trials have based their risk selection algorithm on age and tobacco exposure, but never on pulmonary risk-related biomarkers. In the present study, the baseline inflammatory status, measured by C-reactive protein (CRP) level, and lung function, measured by forced expiratory volume in 1 s (FEV1), were tested as independent predictors of all-cause mortality in LDCT-screening participants. Between 2000 and 2010, 4413 volunteers were enrolled in two LDCT-screening trials, with evaluable baseline CRP and FEV1 values: 2037 were included in the discovery set and 2376 were included in the validation set. The effect of low FEV1 or high CRP alone or combined was evaluated by Kaplan–Meier mortality curves and hazard ratio (HR) with 95% confidence interval (CI) by fitting Cox proportional hazards models. The overall mortality risk was significantly higher in participants with FEV1 of up to 90% (HR: 2.13, CI: 1.43–3.17) or CRP more than 2 mg/l (HR: 3.38, CI: 1.60–3.54) and was still significant in the fully adjusted model. The cumulative 10-year probability of death was 0.03 for participants with FEV1 of more than 90% and CRP up to 2 mg/l, 0.05 with only FEV1 of up to 90% or CRP above 2 mg/l, and 0.12 with FEV1 of up to 90% and CRP above 2 mg/l. This predictive performance was confirmed in the two external validation cohorts with 10-year mortality rates of 0.06, 0.12, and 0.14, and 0.03, 0.07, and 0.14, respectively. Baseline inflammatory status and lung function reduction are independent predictors of all-cause long-term mortality in LDCT-screening participants. CRP and FEV1 could be used to select higher-risk individuals for future LDCT screening and preventive programs.

Effect of Tobacco Smoking Cessation on C-Reactive Protein Levels in A Cohort of Low-Dose Computed Tomography Screening Participants

Smokers have higher levels of C-Reactive Protein (CRP) compared to never smokers. The role of smoking cessation on CRP is still under debate. Using data from two screening studies conducted in Italy in 2000–2010 on 3050 heavy smokers (including 777 ex-smokers), we estimated multivariate odds ratios (OR) for high CRP (i.e. ≥2 mg/L) according to smoking status. Moreover, in a longitudinal analysis based on 975 current smokers, with a second measurement of CRP after an average study period of 3.4 years, we estimated the changes in CRP according to smoking cessation. Prevalence of high CRP at baseline was 35.8% among ex-smokers and 41.1% among current smokers (significant OR for ex- vs. current smokers: 0.79). After four years since smoking cessation, CRP levels significantly decreased with increasing years of cessation (significant OR for ex-smokers since more than 8 years: 0.55). In the longitudinal analysis, no significant reduction in CRP was found for time since smoking cessation (ORs: 1.21, 1.04, and 0.91 for ex-smokers since 1 year, 2–3 years, and ≥4 years, respectively). In the largest prospective study available so far, we found that smoking cessation has a favourable effect on CRP, but this benefit is not evident in the short-term.

Predicting Factors for High-Grade Cervical Dysplasia in Women With Low-Grade Cervical Cytology and Nonvisible Squamocolumnar Junction:

Objective: To assess the risk of developing high-grade cervical dysplasia among women with low-grade cervical cytology and nonvisible squamocolumnar junction (SCJ) at colposcopic examination. Methods: Data of consecutive women with low-grade intraepithelial lesion(≤LSIL) undergoing colposcopic examination, which was unsatisfactory (due to the lack of the visualization of the entire SCJ), were retrospectively reviewed. The risk of developing high-grade cervical intraepithelial neoplasia (CIN2+) was assessed using Kaplan-Meier and Cox models. Results: Data of 86 women were retrieved. Mean (standard deviation [SD]) age was 36.3 (13.4) years. A total of 71 (82.5%) patients had high-risk human papillomavirus (HR-HPV) at the time of diagnosis. Among the 63 patients undergoing repetition of HPV testing, 15 (24%) and 48 (76%) women had positive and negative tests for HR-HPV at 12 months, respectively. We observed that 5 (33%) of 15 patients with HPV persistence developed CIN2+, while only 1 (2%) patient of 48 patients without HPV persistence developed CIN2+ (odds ratio [OR]: 23.5; 95% confidence interval [CI]: 2.46-223.7; P < .001). The length of HR-HPV persistence correlated with an increased risk of developing CIN2+ (P < .001; P for trend). High-risk HPV persistence is the only factor predicting for CIN2+ (hazard ratio: 3.19; 95% CI: 1.55-6.57; P = .002). Conclusions: High-risk HPV persistence predicts the risk of developing CIN2+ in patients with unsatisfactory colposcopic examination. Further studies are warranted in order to implement the use of HPV testing in patients with unsatisfactory colposcopy.

Potential impact of introducing a nonavalent HPV vaccination

To test the theoretical utility of incorporating nonavalent vaccination against HPV into a clinical setting.