SCC may develop after bilharziasis infection (schistosomiasis), the most common cause in these two regions. SCC prognosis improves significantly upon early detection, with a 5-year survival rate of 97%. Cystoscopy and cytology are the most common methods for screening and diagnosis, but the former is invasive and costly, while the latter has poor sensitivity rates. In addition, few studies have examined the sensitivity and specificity of biomarkers in the detection of SCC specifically. Accordingly, Al-Delaimy et al. sought to identify whether three affordable biomarkers – nuclear matrix protein-22 (NMP22), telomerase, and CD44 – could be used to detect SCC in urine samples.
The study was conducted in Egypt and consisted of 60 bladder cancer patients and 60 controls. The mean age was 58.4 years in patients and 40.8 years in controls. Males represented 75% of bladder cancer patients and 45% of controls. Most bladder cancer patients (75%) had a history of schistosomiasis. Microscopic urine analysis revealed that 90% of patients had hematuria and 5% had pyuria. More than 41% of patients had low-grade tumors. In the control group, 20% of participants had urinary tract infections (UTIs), and 30% had urinary tract stones. Urine levels of NMP22 and telomerase were significantly higher in patients compared to controls (approximately tenfold). NMP22 levels were significantly higher in controls with UTI than in other control participants. None of the biomarkers were associated with the cancer stage. Telomerase levels measured by PCR were substantially higher among patients who had a history of schistosomiasis.
The sensitivity of cystoscopy in patients was 68.3%, while the sensitivity for cytology was 70%. NMP22 had a sensitivity of 96.7% and a specificity of 85%. Telomerase had a sensitivity of 87% and a specificity of 88.6%. CD44 had a sensitivity of 45% and a specificity of 86.7%. There was no significant change in validity (as determined by AUC analysis) when NMP22 and telomerase were combined. The authors then used a univariate and multivariate logistic regression analysis to adjust for age and gender differences between patients and controls. The odds ratio for the prediction of bladder cancer was highest for telomerase (1.76), followed by NMP22 (1.14) and CD44 (1.02).
Al-Delaimy et al. demonstrate the feasibility of urine telomerase and NMP22 in detecting SCC. In the context of Egypt, a resource-poor country with high rates of SCC, this finding is significant as it supports the use of this affordable technique for screening. This could also apply to other low- to middle-income countries without access to cystoscopy or regular screening for early diagnosis. Furthermore, SCC detection using these biomarkers is not confounded by urinary conditions such as UTI or renal stones. A significant limitation of this study was the sample size.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
References:
- Al-Delaimy WK, Awadalla A, El-Assmy A, Abol-Enein H, Shokeir A. Comparison of urinary telomerase, CD44, and NMP22 assays for detection of bladder squamous cell carcinoma. Curr Urol. 2022;16(3):154-159. doi:10.1097/CU9.0000000000000098