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PURPOSE Detection of 11 pathogenic variants in the POLE gene in endometrial cancer (EC) is critically important to identify women with a good prognosis and reduce overtreatment. Currently, POLE status is determined by DNA sequencing, which can be expensive, relatively time-consuming, and unavailable in hospitals without specialized equipment and personnel. This may hamper the implementation of POLE-testing in clinical practice. To overcome this, we developed and validated a rapid, low-cost POLE hotspot test by a quantitative polymerase chain reaction (qPCR) assay, QPOLE. MATERIALS AND METHODS Primer and fluorescence-labeled 5′-nuclease probe sequences of the 11 established pathogenic POLE mutations were designed. Three assays, QPOLE-frequent for the most common mutations and QPOLE-rare-1 and QPOLE-rare-2 for the rare variants, were developed and optimized using DNA extracted from formalin-fixed paraffin-embedded tumor tissues. The simplicity of the design enables POLE status assessment within 4-6 hours after DNA isolation. An interlaboratory external validation study was performed to determine the practical feasibility of this assay. RESULTS Cutoffs for POLE wild-type, POLE-mutant, equivocal, and failed results were predefined on the basis of a subset of POLE mutants and POLE wild-types for the internal and external validation. For equivocal cases, additional DNA sequencing is recommended. Performance in 282 EC cases, of which 99 were POLE-mutated, demonstrated an overall accuracy of 98.6% (95% CI, 97.2 to 99.9), a sensitivity of 95.2% (95% CI, 90.7 to 99.8), and a specificity of 100%. After DNA sequencing of 8.8% equivocal cases, the final sensitivity and specificity were 96.0% (95% CI, 92.1 to 99.8) and 100%. External validation confirmed feasibility and accuracy. CONCLUSION QPOLE is a qPCR assay that is a quick, simple, and reliable alternative for DNA sequencing. QPOLE detects all pathogenic variants in the exonuclease domain of the POLE gene. QPOLE will make low-cost POLE-testing available for all women with EC around the globe.

Background Few governments in low and middle-income countries (LMIC) have responded favourably to the international plea for Universal Health Coverage. Childhood cancer survival in LMIC is often below 20%. Limited health-insurance coverage may contribute to this poor survival. Our study explores the influence of health-insurance status on childhood cancer treatment outcomes in a Kenyan academic hospital. Methods This was a retrospective medical records review of all children diagnosed with cancer at Moi Teaching and Referral Hospital between 2010 and 2016. Socio-demographic and clinical data was collected using a structured data collection form. Fisher’s exact test, chi-squared test, Kaplan–Meier method, log-rank test and Cox proportional hazard model were used to evaluate relationships between treatment outcomes and patient characteristics. Study was approved by Institutional Research Ethics Committee. Findings From 2010–2016, 879 children were newly diagnosed with cancer. Among 763 patients whose records were available, 28% abandoned treatment, 23% died and 17% had progressive/relapsed disease resulting in 32% event-free survival. In total 280 patients (37%) had health-insurance at diagnosis. After active enrolment during treatment, total health-insurance registration level reached 579 patients (76%). Treatment outcomes differed by health-insurance status (P < 0.001). The most likely treatment outcome in uninsured patients was death (49%), whereas in those with health-insurance at diagnosis and those who enrolled during treatment it was event-free survival (36% and 41% respectively). Overall survival (P < 0.001) and event-free survival (P < 0.001) were higher for insured versus uninsured patients. The hazard-ratio for treatment failure was 0.30 (95% CI:0.22–0.39; P < 0.001) for patients insured at diagnosis and 0.32 (95% CI:0.24–0.41; P < 0.001) for patients insured during treatment in relation to those without insurance. Interpretation Our study highlights the need for Universal Health Coverage in LMIC. Children without health-insurance had significantly lower survival. Childhood cancer treatment outcomes can be ameliorated by strategies that improve health-insurance access.