Retooling the Pap Smear for Ovarian and Endometrial Cancer Detection

Abstract

Although the Papanicolaou (Pap)2 smear was intended to be used to screen for cervical cancer and its precursors, ovarian and endometrial cancers are infrequently detected via abnormal cervical cytology. However, the diagnostic sensitivity of cytology alone is too low to be clinically useful. A recent publication in Science Translational Medicine (1) demonstrated that DNA mutational analyses of samples collected during the common Pap smear may be capable of detecting ovarian and endometrial cancer. Such a test would be highly advantageous considering that ovarian cancer is usually diagnosed in advanced stages and is highly lethal and that endometrial cancer is the fourth most common cancer in women. Furthermore, no effective screening test exists for either disease. This recent study combined with a prior report (2) provides proof of principle that tumor DNA from the proximal female reproductive tract may be detected in a minimally invasive fashion from the lower tract. Although promising, challenges remain before this concept can be applied as a global screening test for gynecologic cancer. Analyzing disease-specific DNA from Pap smears to enhance cervical pathology screening has been performed clinically for a decade. The recent study (1) exploits DNA stability and newer technological advances to identify abnormalities in the upper genital tract. Before Pap DNA analyses, the primary tumors underwent whole-exome sequencing to identify both anticipated and novel tumor-specific mutated genes. Investigators successfully identified the same mutations within the cervical sample as were in the respective primary tumor for 100% of the endometrial cancers and 41% of the ovarian cancers (1). Several technologic advances are leveraged in this study: ( a ) detecting scarce ovarian cancer DNA from cervical scrapings underscores the sensitivity of the sequencing method used; ( b ) the heterogeneity of each cancer type requires analysis of more …