Accuracy of HPV E6/E7 oncoprotein tests to detect high-grade cervical lesions: a systematic literature review and meta-analysis.

BACKGROUND: Cervical carcinogenesis is mediated by the HPV-E6 and E7 oncoproteins, considered as biomarkers usable in managing screen-positive women. METHODS: We conducted a systematic review and meta-analysis assessing the accuracy of HPV-E6/E7-oncoprotein tests to detect underlying cervical-precancer and cancer. We included studies reporting data on oncoprotein test accuracy detecting cervical intraepithelial neoplasia grade 3 or worse. Random effects logistic regression models were applied for pooling absolute and relative accuracy. RESULTS: Twenty-two studies were included. Sensitivity and specificity estimates ranged from 54.2% (95%CI: 45.2-63.0) to 69.5% (95%CI:60.8-76.9) and from 82.8% (95%CI: 50.4-95.8) to 99.1 (95%CI: 98.8-99.3), respectively in the population irrespective of HPV status. Higher sensitivity estimates ranging from 60.8% (95%CI: 49.6-70.9) to 75.5% (95%CI: 71.7-78.9) but lower specificity estimates ranging from 83.7% (95%CI: 76.1-89.3) to 92.1% (95%CI: 88.5-94.6) were observed in studies enrolling high-risk-HPV-positive women. Studies recruiting only HIV-positive women showed a pooled sensitivity of 46.9% (95%CI: 30.6-63.9) with a specificity of 98.0% (95%CI: 96.8-98.7). CONCLUSIONS: The high specificity of oncoprotein tests supports its use for triaging HPV-positive women. However, oncoprotein-negative women would not be recommended to undertake routine screening, requiring further follow-up. Large-scale and longitudinal studies are needed to further investigate the role of E6/E7-oncoprotein detection in predicting the risk of developing cervical pre-cancer and cancer.

The Effect of Endogenous Cushing Syndrome on All-cause and Cause-specific Mortality.

OBJECTIVE: We aimed to perform a systematic review and meta-analysis of all-cause and cause-specific mortality of patients with benign endogenous Cushing syndrome (CS). METHODS: The protocol was registered in PROSPERO (CRD42017067530). PubMed, EMBASE, CINHAL, Web of Science, and Cochrane Central searches were undertaken from inception to January 2021. Outcomes were the standardized mortality ratio (SMR), proportion, and cause of deaths. The I2 test, subgroup analysis, and meta-regression were used to assess heterogeneity across studies. RESULTS: SMR was reported in 14 articles including 3691 patients (13 Cushing disease [CD] and 7 adrenal CS [ACS] cohorts). Overall SMR was 3.0 (95% CI, 2.3-3.9; I2 = 80.5%) for all CS, 2.8 (95% CI, 2.1-3.7; I2 = 81.2%) for CD and 3.3 (95% CI, 0.5-6.6; I2 = 77.9%) for ACS. Proportion of deaths, reported in 87 articles including 19 181 CS patients (53 CD, 24 ACS, and 20 combined CS cohorts), was 0.05 (95% CI, 0.03-0.06) for all CS subtypes with meta-regression analysis revealing no differences between CS subtypes (P = .052). The proportion of deaths was 0.1 (10%) in articles published before 2000 and 0.03 (3%) in 2000 until the last search for CS (P < .001), CD (P < .001), and ACS (P = .01). The causes of death were atherosclerotic diseases and thromboembolism (43.4%), infection (12.7%), malignancy (10.6%), active disease (3.5%), adrenal insufficiency (3.0%), and suicide (2.2%). Despite improved outcomes in recent years, increased mortality from CS persists. The causes of death highlight the need to prevent and manage comorbidities in addition to treating hypercortisolism.