Background: We conducted a systematic review and meta-analysis to assess efficacy and safety of prophylactic HPV vaccines against cervical cancer precursor events in women. Methods: Randomized-controlled trials of HPV vaccines were identified from MEDLINE, Cochrane Central Register of Controlled Trials, conference abstracts and references of identified studies, and assessed by two independent reviewers. Efficacy data were synthesized using fixed-effect models, and evaluated for heterogeneity using I² statistic. Results: Seven unique trials enrolling 44,142 females were included. The fixed-effect Relative Risk (RR) and 95% confidence intervals were 0.04 (0.01-0.11) and 0.10 (0.03-0.38) for HPV-16 and HPV 18-related CIN2+ in the per-protocol populations (PPP). The corresponding RR was 0.47 (0.36-0.61) and 0.16 (0.08-0.34) in the intention-to-treat populations (ITT). Efficacy against CIN1+ was similar in scale in favor of vaccine. Overall vaccines were highly efficacious against 6-month persistent infection with HPV 16 and 18, both in the PPP cohort (RR: 0.06 [0.04-0.09] and 0.05 [0.03-0.09], respectively), and the ITT cohorts (RR: 0.15 [0.10-0.23] and 0.24 [0.14-0.42], respectively). There was limited prophylactic effect against CIN2+ and 6-month persistent infections associated with non-vaccine oncogenic HPV types. The risk of serious adverse events (RR: 1.00, 0.91-1.09) or vaccine-related serious adverse events (RR: 1.82; 0.79-4.20) did not differ significantly between vaccine and control groups. Data on abnormal pregnancy outcomes were underreported. Conclusions: Prophylactic HPV vaccines are safe, well tolerated, and highly efficacious in preventing persistent infections and cervical diseases associated with vaccine-HPV types among young females. However, long-term efficacy and safety needs to be addressed in future trials.

Background: Lung cancer is considered a terminal illness with a five-year survival rate of about 16%. Informed decision-making related to the management of a disease requires accurate prognosis of the disease with or without treatment. Despite the significance of disease prognosis in clinical decision-making, systematic assessment of prognosis in patients with lung cancer without treatment has not been performed. We conducted a systematic review and meta-analysis of the natural history of patients with confirmed diagnosis of lung cancer without active treatment, to provide evidence-based recommendations for practitioners on management decisions related to the disease. Specifically, we estimated overall survival when no anticancer therapy is provided. Methods: Relevant studies were identified by search of electronic databases and abstract proceedings, review of bibliographies of included articles, and contacting experts in the field. All prospective or retrospective studies assessing prognosis of lung cancer patients without treatment were eligible for inclusion. Data on mortality was extracted from all included studies. Pooled proportion of mortality was calculated as a back-transform of the weighted mean of the transformed proportions using the random-effects model. To perform meta-analysis of median survival, published methods were used to pool the estimates as mean and standard error under the random-effects model. Methodological quality of the studies was examined. Results: Seven cohort studies (4,418 patients) and 15 randomized controlled trials (1,031 patients) were included in the meta-analysis. All studies assessed mortality without treatment in patients with non-small cell lung cancer (NSCLC). The pooled proportion of mortality without treatment in cohort studies was 0.97 (95% CI: 0.96 to 0.99) and 0.96 in randomized controlled trials (95% CI: 0.94 to 0.98) over median study periods of eight and three years, respectively. When data from cohort and randomized controlled trials were combined, the pooled proportion of mortality was 0.97 (95% CI: 0.96 to 0.98). Test of interaction showed a statistically non-significant difference between subgroups of cohort and randomized controlled trials. The pooled mean survival for patients without anticancer treatment in cohort studies was 11.94 months (95% CI: 10.07 to 13.8) and 5.03 months (95% CI: 4.17 to 5.89) in RCTs. For the combined data (cohort studies and RCTs), the pooled mean survival was 7.15 months (95% CI: 5.87 to 8.42), with a statistically significant difference between the two designs. Overall, the studies were of moderate methodological quality. Conclusion: Systematic evaluation of evidence on prognosis of NSCLC without treatment shows that mortality is very high. Untreated lung cancer patients live on average for 7.15 months. Although limited by study design, these findings provide the basis for future trials to determine optimal expected improvement in mortality with innovative treatments.