Research Summary

My research program is aimed at better understanding the changes in the microenvironment of the human that accompany infection with and the carcinogenic effects of human papillomavirus (HPV). My previous studies indicated that HPV infection of the cervix recruits a robust immune response resulting in the development of germinal centers, indicating that the cervix is a site of mucosal-associated lymphoid tissue (MALT). The finding that HPV results in recruitment of HIV target cells led me to hypothesize that cervical HPV infection might result in increased risk of HIV acquisition. I validated this hypothesis in a large cohort study in Zimbabwe in the context of a clinical trial of HIV prevention, funded by the Bill and Melinda Gates Foundation. I have collaborated with an international team of scientists exploring the distribution and diversity of HPV 58, which is common in sub-Saharan Africa. I have also collaborated extensively with Dr. Megan Huchko at UCSF studying the optimal cervical cancer screening methods for women with HIV in Kenya. My recent research is focused on the mechanisms by which perturbations of the cervical microenvironment by HPV or microbicides might enhance susceptibility to HIV acquisition in women living in high prevalence regions. As a physician scientist, I am Director of the UCSF Dysplasia Clinic and am involved clinically in the care and treatment of women with cervical abnormalities.

Research Funding

  • April 1, 2014 - March 31, 2018 - Reproductive Tract Effects of the Intrauterine Device: Implications for HIV Risk , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI111925
  • September 1, 2009 - August 31, 2015 - Exploring HIV-Host Interactions in the Female Reproductive Tract , Principal Investigator . Sponsor: NIH, Sponsor Award ID: P01AI083050
  • December 1, 1974 - March 31, 2009 - General Clinical Research Center , Co-Investigator . Sponsor: NIH, Sponsor Award ID: M01RR000079
  • September 15, 2000 - August 31, 2003 - MOLECULAR APPROACHES TO CERVICAL CANCER SCREENING , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA080780

Education

McGill University, B.Sc., 1975, Biochem (Honors)
University of Cambridge, Diploma, 1976, Hist. & Phil. of Sci.
Rockefeller University, Ph.D., 1982
Stanford University, M.D., 1986

Honors & Awards

  • 1986-1987
    Julius R. Krevans Award for Clinical Excellence
  • 1990
    Elected to Alpha Omega Alpha by the graduating medical class of 1990, UCSF
  • 1990
    Teaching Award from the graduating medical school class
  • 1998-present
    John Kerner Endowed Chair of Reproductive Biology
  • 1998
    Colposcopy Recognition Award, American Society of Colposcopy and Cervical Pathology
  • 2000-present
    Associate Member, Early Detection Research Network, NCI
  • 2006
    Award of Merit, American Society of Colposcopy and Cervical Pathology

Selected Publications

  1. Silverberg MJ, Leyden WA, Lam JO, Chao CR, Gregorich SE, Huchko MJ, Kulasingam S, Kuppermann M, Smith-McCune KK, Sawaya GF. Effectiveness of 'catch-up' human papillomavirus vaccination to prevent cervical neoplasia in immunosuppressed and non-immunosuppressed women. Vaccine. 2020 06 15; 38(29):4520-4523.  View on PubMed
  2. Shanmugasundaram U, Critchfield JW, Giudice LC, Smith-McCune K, Greenblatt RM, Shacklett BL. Parallel studies of mucosal immunity in the reproductive and gastrointestinal mucosa of HIV-infected women. Am J Reprod Immunol. 2020 07; 84(1):e13246.  View on PubMed
  3. Smith-McCune K, Thomas R, Averbach S, Seidman D, Takeda M, Houshdaran S, Giudice LC. Differential Effects of the Hormonal and Copper Intrauterine Device on the Endometrial Transcriptome. Sci Rep. 2020 04 23; 10(1):6888.  View on PubMed
  4. Houshdaran S, Chen JC, Vallvé-Juanico J, Balayan S, Vo KC, Smith-McCune K, Greenblatt RM, Irwin JC, Giudice LC. Progestins Related to Progesterone and Testosterone Elicit Divergent Human Endometrial Transcriptomes and Biofunctions. Int J Mol Sci. 2020 Apr 09; 21(7).  View on PubMed
  5. Cavrois M, Hilton JF, Roan NR, Takeda M, Seidman D, Averbach S, Chang E, Raman N, Greenblatt R, Shacklett BL, Smith-McCune K. Effects of the levonorgestrel-containing intrauterine device, copper intrauterine device, and levonorgestrel-containing oral contraceptive on susceptibility of immune cells from cervix, endometrium and blood to HIV-1 fusion measured ex vivo. PLoS One. 2019; 14(8):e0221181.  View on PubMed
  6. Sawaya GF, Sanstead E, Alarid-Escudero F, Smith-McCune K, Gregorich SE, Silverberg MJ, Leyden W, Huchko MJ, Kuppermann M, Kulasingam S. Estimated Quality of Life and Economic Outcomes Associated With 12 Cervical Cancer Screening Strategies: A Cost-effectiveness Analysis. JAMA Intern Med. 2019 07 01; 179(7):867-878.  View on PubMed
  7. Sawaya GF, Smith-McCune K, Kuppermann M. Cervical Cancer Screening: More Choices in 2019. JAMA. 2019 May 28; 321(20):2018-2019.  View on PubMed
  8. Reynoso-Prieto M, Takeda M, Prakobphol A, Seidman D, Averbach S, Fisher S, Smith-McCune K. Menstrual cycle-dependent alterations in glycosylation: a roadmap for defining biomarkers of favorable and unfavorable mucus. J Assist Reprod Genet. 2019 May; 36(5):847-855.  View on PubMed
  9. Silverberg MJ, Leyden WA, Lam JO, Gregorich SE, Huchko MJ, Kulasingam S, Kuppermann M, Smith-McCune KK, Sawaya GF. Effectiveness of catch-up human papillomavirus vaccination on incident cervical neoplasia in a US health-care setting: a population-based case-control study. Lancet Child Adolesc Health. 2018 10; 2(10):707-714.  View on PubMed
  10. Averbach S, Silverberg MJ, Leyden W, Smith-McCune K, Raine-Bennett T, Sawaya GF. Recent intrauterine device use and the risk of precancerous cervical lesions and cervical cancer. Contraception. 2018 Apr 17.  View on PubMed
  11. Silverberg MJ, Leyden WA, Chi A, Gregorich S, Huchko MJ, Kulasingam S, Kuppermann M, Seto A, Smith-McCune KK, Sawaya GF. Human Immunodeficiency Virus (HIV)- and Non-HIV-Associated Immunosuppression and Risk of Cervical Neoplasia. Obstet Gynecol. 2018 01; 131(1):47-55.  View on PubMed
  12. Sawaya GF, Smith-McCune KK, Gregorich SE, Moghadassi M, Kuppermann M. Effect of professional society recommendations on women's desire for a routine pelvic examination. Am J Obstet Gynecol. 2017 09; 217(3):338.e1-338.e7.  View on PubMed
  13. Ho D, Drake TK, Smith-McCune KK, Darragh TM, Hwang LY, Wax A. Feasibility of clinical detection of cervical dysplasia using angle-resolved low coherence interferometry measurements of depth-resolved nuclear morphology. Int J Cancer. 2017 03 15; 140(6):1447-1456.  View on PubMed
  14. Smith-McCune KK, Hilton JF, Shanmugasundaram U, Critchfield JW, Greenblatt RM, Seidman D, Averbach S, Giudice LC, Shacklett BL. Effects of depot-medroxyprogesterone acetate on the immune microenvironment of the human cervix and endometrium: implications for HIV susceptibility. Mucosal Immunol. 2017 09; 10(5):1270-1278.  View on PubMed
  15. Averbach SH, Ma Y, Smith-McCune K, Shiboski S, Moscicki AB. The effect of intrauterine devices on acquisition and clearance of human papillomavirus. Am J Obstet Gynecol. 2017 Apr; 216(4):386.e1-386.e5.  View on PubMed
  16. Wu TJ, Smith-McCune K, Reuschenbach M, von Knebel Doeberitz M, Maloba M, Huchko MJ. Performance of p16INK4a ELISA as a primary cervical cancer screening test among a large cohort of HIV-infected women in western Kenya: a 2-year cross-sectional study. BMJ Open. 2016 09 13; 6(9):e012547.  View on PubMed
  17. Shanmugasundaram U, Hilton JF, Critchfield JW, Greenblatt RM, Giudice LC, Averbach S, Seidman D, Shacklett BL, Smith-McCune K. Effects of the levonorgestrel-releasing intrauterine device on the immune microenvironment of the human cervix and endometrium. Am J Reprod Immunol. 2016 08; 76(2):137-48.  View on PubMed
  18. Seidman D, Hemmerling A, Smith-McCune K. Emerging Technologies to Prevent Pregnancy and Sexually Transmitted Infections in Women. Semin Reprod Med. 2016 May; 34(3):159-67.  View on PubMed
  19. Sawaya GF, Smith-McCune K. Cervical Cancer Screening. Obstet Gynecol. 2016 Mar; 127(3):459-467.  View on PubMed
  20. Seidman D, Averbach S, Smith-McCune K, Darney P. Interpretation, communication, and mechanisms of associations between injectable contraception and HIV risk. Lancet HIV. 2015 Sep; 2(9):e365-6.  View on PubMed

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