Continued partnership between Gynecologists and Cytopathologists in the era of molecular medicine to prevent cervical, ovarian and breast cancers
Session Title: Continued partnership between gynecologists and cytopathologists in the era of precision molecular personalized medicine for better women’s health care
Keynote Speaker: Sin Hang Lee, MD, F.R.C.P.(C), FCAP, Director, Milford Molecular Diagnostics Laboratory, Milford, CT
Highlights: Sanger sequencing on 10% of the cells in a Pap cytology vial for:
· Affordable 3 BRCA 1&2 founder mutations screen
· Extremely sensitive, no-false-positive HPV detection/genotyping
· Extremely sensitive, no-false-positive testing for Chlamydia infection and gonorrhea.
1. Lee SH, Zhou S, Zhou T, Hong G. Sanger Sequencing for BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del Mutation Screen on Pap Smear Cytology Samples. International Journal of Molecular Sciences. 2016; 17(2):229. http://www.mdpi.com/1422-0067/17/2/229
2. Lee SH, Vigliotti VS, Pappu S. DNA sequencing validation of Chlamydia trachomatis and Neisseria gonorrhoeae nucleic acid tests. Am J Clin Pathol. 2008;129(6):852-9.
3. Stoler MH. Advances in cervical screening technology. Mod Pathol. 2000, 13, 275–284.
4. Austin RM, Zhao C. Is 58% sensitivity for detection of cervical intraepithelial neoplasia 3 and invasive cervical cancer optimal for cervical screening? Cytojournal. 2014 May 22;11:14.
The cervical screening partnership between gynecologists and cytopathologists has lowered the number of cervical cancer deaths to about 4,000 per year, representing a 70% reduction in the United States. In comparison, 40,290 women and 14,180 women are still expected to die of breast cancer and ovarian cancer each year, respectively, due to a lack of effective cancer risk screening tools for the latter two malignancies. Since the carriers of the germline BRCA1 185delAG, BRCA1 5382insC and BRCA2 6174delT mutations are known to be at high risk of developing breast cancer and ovarian cancer, universal screening for these 3 mutations for all women at age 30 has been recommended if the cost for such screening can be markedly reduced and the quality of the tests can be assured [King MC, et al. JAMA 2014;312:1091-1092. ]. Presymptomatic salpingo-oophorectomy for these high-risk women after child-bearing ages can reduce breast cancers and ovarian cancers as well as overall mortality [ http://www.acog.org/About-ACOG/News-Room/News-Releases/2009/Routine-Screening-for-Hereditary-Breast-and-Ovarian-Cancer-Recommended ]. The author will present a simplified technology to use liquid-based Pap smear cytology specimens (SurePath® or ThinPrep®) to detect single nucleotide deletions and insertions by Sanger sequencing for the detection of these BRCA mutations.
If these 3 BRCA mutations are tested in conjunction with Pap smear and HPV assays, the cost may be reduced to $200 per test since all the reagents are generic and inexpensive.