Santhosh Kuriakose

High prevalence of “non‐pathogenic” POLE mutation with poor prognosis in a cohort of endometrial cancer from South India

AbstractObjectiveThe Cancer Genome Atlas (TCGA) project identified favorable prognosis regarding the ultra‐mutated endometrial cancer (EC) subtype linked to polymerase epsilon gene (POLE) mutations. This study investigated POLE mutations in EC of Indian patients.MethodsThis retrospective analytical study was conducted between January 2016 and January 2023 at the Government Medical College, Kozhikode, and the MVR Cancer Center, Kozhikode, Kerala. Sanger sequencing of POLE gene exons 9 and 13 in 151 EC patients was carried out to analyze the relationship between mutations and epidemiological factors, clinicopathologic features, and treatment outcomes.ResultsAmong 151 cases enrolled, 39 were unique POLE‐mutated cases. Significant associations were high‐grade tumors, myometrial invasion >50%, and Lymph‐vascular space invasion (LVSI). The median follow‐up was 40 months (95% confidence interval [CI], 34–46). A lower mean disease‐specific survival (DSS) of 51.7 months (95% CI, 43.7–59.6) was noted in the POLE‐mutated group compared with 72.11 months (95% CI, 67.60–76.62) for the POLE wild‐type. A statistically significant hazard ratio (HR) of 2.683 for DSS in the POLE‐mutated group was noted. In advanced stages (FIGO stages II–IV), a nine‐fold HR for DSS and overall survival (OS) compared with POLE wild‐type was identified. After controlling for treatment effects using Cox proportional HR, advanced‐stage POLE‐mutated tumors had a significantly higher HR of 8.67 for DSS compared with POLE‐wild‐type tumors of the same stage.ConclusionThis study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE‐mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change.

Human papillomavirus (HPV) DNA detection in uterine cervix cancer after radiation indicating recurrence: a systematic review and meta-analysis

The causal association of human papillomavirus (HPV) in uterine cervical cancer was well established and this oncogenic virus was reported to be a biomarker for overall recurrence and central pelvic recurrence. The objective of the present systematic review and meta-analysis was to assess the role of HPV DNA testing in early detection of recurrence among cervical cancer survivors after radiotherapy. We performed a systematic review and meta-analysis by means of searching electronic databases for published articles between January 1984 and June 2018, on the basis of standard systematic review guidelines prescribed by major agencies namely Cochrane Collaboration (https://www.cochrane.org) and Campbell Collaboration (https://www.campbellcollaboration.org). The meta-analysis component was further modified appropriately for the synthesis of sensitivity and specificity results. A total of 1,055 cervical cancer cases who had received pelvic radiation with or without chemotherapy from ten cohort studies were evaluated. The overall pooled sensitivity and specificity of HPV DNA testing was 0.84 (95% confidence interval [CI]= 0.66-0.94) and 0.35 (95% CI=0.20-0.54) respectively. The positive likelihood ratio was 1.3 (95% CI=1.0-1.7) and the negative likelihood ratio was 0.45 (95% CI=0.18-1.10) with an estimated diagnostic odds ratio of 3 (95% CI=1-9). The screening for HPV DNA testing during follow-up facilitates early detection of recurrence after radiotherapy.