University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Karen K. Smith-McCune, MD, PhD

Karen K. Smith-McCune, MD, PhD

Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences, UCSF
John A. Kerner Chair in Gynecologic Oncology, UCSF

Cancer Center Program Memberships

Affiliate Member

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.


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

Professional Experience

  • 1986-1990
    UCSF, Resident in Ob/Gyn
  • 1990-1993
    Fellow, UCSF, lab of Dr. J. Michael Bishop
  • 1991-present
    Director, Dysplasia Clinic, UCSF
  • 1994-1995
    Assistant Adjunct Professor, Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF
  • 1995-2002
    Assistant Professor, Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF
  • 2002-2010
    Associate Professor, Department of Obstetrics, Gynecology & Reproductive Sciences, UCSF
  • 2010-present
    Professor, Department of Obstetrics, Gynecology & Reproductive Sciences, UCSF

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

  • Smith-McCune K and Weidner N. Demonstration and Characterization of the Angiogenic Properties of Cervical Dysplasia. Cancer Res 1994;54:800-804. PMID: 7508337
  • Smith-McCune K, Zhu Y-H, Hanahan D, and Arbeit J. Cross-species Comparison of Angiogenesis during the Premalignant Stages of Squamous Carcinogenesis in the Human Cervix and K14-HPV16 Transgenic Mice. Cancer Research 1997;57:1294-1300. PMID: 9102216
  • Suh-Burgmann E, Darragh T, Smith-McCune K. Atypical squamous cells of undetermined significance: Management patterns at an academic medical center. Am J Obstet Gynecol 1998;178:991-995. PMID: 9609573
  • Smith-McCune K, Kallman D, Robbins CA, Shivakumar S, Yuschenkoff L, and Bishop JM. Intraanuclear localization of human papillomavirus 16 E7 during transformation and preferential binding of E7 to the Rb family member p130. PNAS 1999;96:6999-7004. PMID: 10359828
  • A McGaraghan and K. Smith-McCune Follow-up of unsatisfactory Pap test results. JAMA 283:1290-1, 2000.
  • Smith-McCune, K, Mancuso V, Contant T, and R. Jackson. Management of abnormal Pap smears by Board-certified gynecologists: Discrepancies with recommendations of the Bethesda system. Am J Obstet Gynecol 2001;185:551-556. PMID: 11568776
  • A Kobayashi, Darragh T, Herndier B, Anastos K, Minkoff H, Cohen M, Young M, Levine A, Ahdieh L, Weinberg V, Hyun W, Greenblatt R, Smith-McCune K. Lymphoid Follicles are Generated in High Grade Cervical Dysplasia and have Differing Characteristics Depending on HIV Status. Am J Pathol 2002;160:151-64. PMID: 11786409
  • Lamarcq LH, Deeds J, Ginzinger D, Perry J, Padmanabha S, and Smith-McCune K. Measurement of E7 transcripts by real time quantitative RT-PCR in samples collected for cervical cancer screening. J Mol Diagn 2002;4:97-102. PMID: 11986400
  • Sawaya G and Smith-McCune K. Testing for human papillomavirus in women with abnormal Pap smear results [letter]. JAMA 2002;288:1350-51. PMID: 12234220
  • Lee C, Mancuso V, Contant T, Jackson R, Smith-McCune K. Management of women with low-grade squamous intraepithelial lesions on cytology or biopsy by board-certified gynecologists. Am J Obstet Gynecol 2003;188: 693-8. PMID: 12634642
  • Chen Y, Miller C, Mosher R, Zhao X, Deeds J, Bryant B, Yang D, Meyer R, Cronin F, Gostout BS, Smith-McCune K and Schlegel R. Identification of cervical cancer markers by cDNA and tissue microarrays, Cancer Res 2003;63:1927-35. PMID: 12702585
  • Ancheta E, Perry J, Bernard-Pearl L, Paul T, Darragh T and Smith-McCune K. Participants at the ASCCP 2000 Biennial Meeting Adhere to Published Guidelines in Their Management of Atypical Squamous Cells and Atypical Glandular Cells on Pap Test. Journal of Lower Genital Tract Disease 2003:7;279-84. PMID: 17051084
  • Kobayashi A, Greenblatt RM, Anastos K, Minkoff H, Massad SL, Young M, Levine AM, Darragh TM, Weinberg V, and Smith-McCune KK. Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection. Cancer Res, 2004:64; 6766-74. PMID: 15374995
  • Cheng KW, Lahad JP, Kuo WL, Lapuk A, Yamada K, Auersperg N, Liu J, Smith-McCune K, Lu KH, Fishman D, Gray JW, Mills GB. The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat Med 2004:10;1251-6. PMID: 15502842
  • Nanjundan M, Zhang F, Schmandt R, Smith-McCune K, and Mills GB. Identification of a novel splice variant of AML1b in ovarian cancer patients conferring loss of wild-type tumor suppressive functions.Oncogene 2007;26:2574-84. PMID: 17072347
  • Nanjundan M, Nakayama Y, Cheng KW, Lahad J, Liu J, Lu K, Kuo WL, Smith-McCune K, Fishman D, Gray JW, Mills GB. Amplification of MDS1/EVI1 and EVI1, located in the 3q26.2 amplicon, is associated with favorable patient prognosis in ovarian cancer. Cancer Res. 2007;67:3074-84. PMID: 17409414
  • Sawaya GF, Smith-McCune K. HPV vaccination--more answers, more questions. N Engl J Med. 2007;356:1991-3. PMID: 17494933
  • Partridge EE, Abu-Rustum N, Campos S, Fahey PJ, Greer BE, Lele SM, Lieberman RW, Lipscomb GH, Morgan M, Nava ME, Reynolds RK, Singh DK, Smith-McCune K , Teng N, Trimble CL, Valea F, Wilczynski S, National Comprehensive Cancer Network. Cervical cancer screening. J Natl Compr Canc Netw. 2008:6:58-82. PMID: 18267060
  • Kobayashi A, Weinberg V, Darragh T, Smith-McCune K. Evolving immunosuppressive microenvironment during human cervical carcinogenesis, Mucosal Immunol 2008;1:412-420. PMID: 19079205
  • Smith-McCune KK [editorial]. Human papillomavirus vaccine efficacy: aligning expectations with reality. Gynecol Oncol 2008:111;1-2. PMID: 18922296
  • Sawaya GF, Chirenje MZ, Magure T, Tuveson J, Ma Y, Shiboski S, Da Costa M, Palefsky JM, Moscicki AB, Mutasa R, Chipato T, Smith-McCune K. Effect of diaphragm and lubricant gel provision on human papillomavirus infection among women provided condoms. Obstet Gynecol 2008 112(5):990-997. PMID: 18978097
  • Nanjundan M, Cheng KW, Zhang F, Lahad J, Kuo WL, Schmandt R, Smith-McCune K, Fishman D, Gray JW, Mills GB. Overexpression of SnoN/SkiL, amplified at the 3q26.2 locus, in ovarian cancers: a role in ovarian pathogenesis. Mol Oncol. 2008:2;164-81. PMID: 19383336
  • Roan NR, Munch J, Arhel N, Mothes W, Neidelman J, Kobayashi A, Smith-McCune K, Kirchhoff F, Greene WC. The cationic properties of SEVI underlie its ability to enhance human immunodeficiency virus infection. J Virol 2009:83:73-80. PMID: 18945786
  • Fukuchi E, Sawaya GF, Chirenje M, Magure T, Tuveson J, Ma Y, Shiboski S, Da Costa M, Palefsky J, Moscicki AB, Mutasa R, Chipato T, Smith-McCune K. Cervical human papillomavirus incidence and persistence in a cohort of HIV-negative women in Zimbabwe. Sex Transm Dis. 2009;36:305-11.PMID: 19295468
  • Rahangdale L, Greenblatt RM, Perry J, Darragh TM, Kobayashi A, Smith-McCune KK. In vivo effects of nonoxynol-9 on endometrial immune cell populations. J Acquir Immune Defic Syndr. 52:137-9, 2009.PMID: 1970426
  • Smith-McCune K, Sawaya GF. Update on quadrivalent human papillomavirus vaccination and pregnancy outcomes: is contraception advisable? Obstet Gynecol 114(6):1168-9, 2009. PMID: 19935015
  • Smith-McCune KK, Shiboski S, Chirenje ZM, Magure T, Tuveson J, Ma Y, DaCosta M, Moscicki AB, Palefsky J, Makunike-Mutasa J, Chipato T, van der Straten A, Sawaya GF Type-specific Cervico-Vaginal Human Papillomavirus Infection Increases Risk of HIV Acquisition Independent of Other Sexually Transmitted Infections, in press, PLoS ONE.