Michelle Joanne Khan, MD, MPH, FACOG (she/her)

All Publications

• Cervical Cancer Screening: Evolution of National Guidelines and Current Recommendations. Clinical obstetrics and gynecology Khan, M. J. 2023

  Abstract

  Cancer of the cervix is preventable through vaccination against human papillomavirus and by screening and treatment of cervical precancers. Cervical cancer screening has evolved since the Pap smear was first discovered in the 1920s. Current guidelines from the US Preventive Services Task Force and the American Cancer Society incorporate the use of cervical cytology and high-risk human papillomavirus tests performed every 3 to 5 years for screening in average-risk asymptomatic patients. Testing should begin at age 21 to 25 years old and stop at 65 years old if sufficient cessation criteria has been met.

  View details for DOI 10.1097/GRF.0000000000000791

  View details for PubMedID 37436937

• Retrospective Screening of Clinical Samples for Monkeypox Virus DNA, California, USA, 2022. Emerging infectious diseases Contag, C. A., Lu, J., Renfro, Z. T., Karan, A., Salinas, J. L., Khan, M., Solis, D., Sahoo, M. K., Yamamoto, F., Pinsky, B. A. 2023; 29 (4): 848-850

  Abstract

  We retrospectively screened oropharyngeal and rectal swab samples originally collected in California, USA, for Chlamydia trachomatis and Neisseria gonorrhoeae testing for the presence of monkeypox virus DNA. Among 206 patients screened, 17 (8%) had samples with detectable viral DNA. Monkeypox virus testing from mucosal sites should be considered for at-risk patients.

  View details for DOI 10.3201/eid2904.221576

  View details for PubMedID 36918374

  View details for PubMedCentralID PMC10045697

• Scattering-Based Light-Sheet Microscopy Imaging of HPV-Associated Squamous Lesions of the Lower Anogenital Tract: A Pilot Study for In-Vivo Microscopy Applications in Anal Cancer Screening Liang, B., Zhao, J., Forgone, E., Khan, M., Kang, D., Yang, E. ELSEVIER SCIENCE INC. 2023: S1554

  View details for Web of Science ID 000990969803251

• Investigation of different wavelengths for scattering-based light sheet microscopy. Biomedical optics express Zhao, J., Kulkarni, N., Dobo, E., Khan, M. J., Yang, E., Kang, D. 2022; 13 (7): 3882-3892

  Abstract

  Scattering-based light sheet microscopy (sLSM) is a microscopy technique that can visualize cellular morphologic details based on the scattering signal. While sLSM was previously shown to image animal tissues ex vivo at a cellular resolution, the wavelength used was chosen based on other in vivo microscopy technologies rather than through a comparison of the sLSM imaging performance between different wavelengths. In this paper, we report the development of a multi-wavelength sLSM setup that facilitates the investigation of different wavelengths for sLSM imaging. Preliminary results of imaging human anal tissues ex vivo showed that the sLSM setup allowed for comparisons of the cellular imaging performance at the same tissue location between different wavelengths. Both the quantitative analysis of the image contrast and the visual assessment by a pathologist showed that the imaging depth increased with wavelength, and the imaging depth increase was most notable around 600 nm. The preliminary results showed that the multi-wavelength sLSM setup could be useful in identifying the optimal wavelength for the specific tissue type.

  View details for DOI 10.1364/BOE.459823

  View details for PubMedID 35991931

  View details for PubMedCentralID PMC9352285

• 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. Journal of lower genital tract disease Perkins, R. B., Guido, R. S., Castle, P. E., Chelmow, D., Einstein, M. H., Garcia, F., Huh, W. K., Kim, J. J., Moscicki, A. B., Nayar, R., Saraiya, M., Sawaya, G. F., Wentzensen, N., Schiffman, M. 2020; 24 (2): 102-131

  View details for DOI 10.1097/LGT.0000000000000525

  View details for PubMedID 32243307

  View details for PubMedCentralID PMC7147428

• Challenges Associated With Cervical Cancer Screening and Management in Obese Women: A Provider Perspective. Journal of lower genital tract disease Clarke, M. A., Massad, L. S., Khan, M. J., Smith, K. M., Guido, R. S., Mayeaux, E. J., Darragh, T. M., Huh, W. K., Johnson, A. L., Gold, M. A., Schiffman, M., Wentzensen, N. 2020; 24 (2): 184-191

  Abstract

  Obese women are at increased risk of cervical cancer, partly due to missed detection of cervical precancers during routine cervical cancer screening. We administered a clinician survey to better understand specific challenges and identify potential solutions to performing cervical cancer screening and management in obese women.We administered a web-based survey to 2,319 members of the American Society of Colposcopy and Cervical Pathology including questions related to challenges associated with cervical sampling and visualization in obese compared with normal weight women and potential strategies for improvement. We summarized providers' responses using descriptive statistics and used Fisher exact tests to evaluate associations between provider characteristics and challenges with cervical sampling, visualization, and biopsy.Of the 240 providers that completed the survey, 89% and 93% reported that cervical sampling and visualization are more challenging in obese women, respectively, whereas 80% reported that taking a biopsy was more challenging. Commonly reported barriers included vaginal prolapse, difficulty visualizing and accessing the cervix, and lack of long enough sampling devices and large enough speculums. Frequently used techniques to improve sampling and visualization included use of a condom or examination glove finger to sheath a speculum and using a tenaculum. Most providers identified training for cervical sampling and colposcopy in obese women as a learning gap, and only 8% reported receiving such training.Cervical cancer screening and management are more challenging in obese compared with normal weight women. Major barriers to cervical sampling and visualization included lack of adequately sized equipment and lack of education and training.

  View details for DOI 10.1097/LGT.0000000000000506

  View details for PubMedID 32243314

• HIV Status and Other Risk Factors for Prevalent and Incident Sexually Transmitted Infection during Pregnancy (2000-2014). Infectious diseases in obstetrics and gynecology Dionne-Odom, J., Khan, M. J., Jauk, V. C., Szychowski, J., Long, D. M., Wallace, S., Neely, C., Fry, K., Marrazzo, J., Crain, M., Tita, A. T. 2019; 2019: 6584101

  Abstract

  Sexually transmitted infections (STIs) are associated with adverse birth outcomes. Current prenatal STI screening guidelines define "risk" without explicit consideration of HIV status. Our objective was to test the hypothesis that HIV status is associated with bacterial STI in pregnant women.We designed a retrospective cohort study to identify pregnant women with HIV who delivered at our facility during 2000-2014. HIV+ women were compared to HIV- women with matching by year of delivery. Logistic regression was used to model adjusted odds of prevalent and incident STI. Prevalent STI was defined as chlamydia (CT), gonorrhea (GC), syphilis, or trichomoniasis detected on an initial prenatal screening test and incident STI as a newly positive result following a negative prenatal test.The cohort included 432 women, 210 HIV+ and 222 HIV-. Most pregnant women were screened for STI (92% of HIV+ women and 74% of HIV- women). STI rates were high and particularly elevated in HIV+ women: 29% vs 18% (p=0.02), for prevalent STI and 11% vs 2% (p<0.001) for incident STI. Risk factors for prevalent STI were as follows: HIV status (aOR 3.0, CI: 1.4-6.4), Black race (aOR 2.7, 95% CI: 1.1-6.6), and more recent delivery (2007-2014 compared to 2000-2006) (aOR 2.3, CI: 1.1-4.7). HIV status was an independent risk factor for incident STI (aOR 7.2, CI: 2.1-25.0).Pregnant women who delivered in our center had high STI rates. Since HIV infection was independently associated with prevalent and incident STI, prenatal screening guidelines may need to incorporate HIV status as a high-risk group for repeat testing.

  View details for DOI 10.1155/2019/6584101

  View details for PubMedID 31057323

  View details for PubMedCentralID PMC6463595

• HIV Status and Contraceptive Utilization among Women in Cameroon. Journal of the International Association of Providers of AIDS Care Budhwani, H., Hearld, K. R., Dionne-Odom, J., Manga, S., Nulah, K., Khan, M., Welty, T., Welty, E., Tita, A. T. 2019; 18: 2325958219826596

  Abstract

  We examined patterns of contraceptive utilization by HIV status among women in Cameroon, hypothesizing that women living with HIV would utilize contraception at higher rates than their HIV-negative peers.Deidentified, clinical data from the Cameroon Baptist Convention Health Services (2007-2013) were analyzed (N = 8995). Frequencies compared outcomes between women living with HIV (15.1%) and uninfected women. Multivariate analyses examined associates of contraceptive utilization and desire to become pregnant.Contraceptive utilization was associated with higher education, living with HIV, monogamy, and higher parity ( P < .001). Women living with HIV had 66% higher odds of using contraceptives than their negative peers (odds ratio [OR]: 1.66, confidence interval [CI]: 1.45-1.91, P < .001). Polygamous women had 37% lower odds of using contraceptives compared to monogamous women (OR: 0.63, 95% CI: 0.52-0.75, P < .001).Increasing contraceptive utilization in resource-constrained settings should be a priority for clinicians and researchers. Doing so could improve population health by reducing HIV transmission between partners and from mother to child.

  View details for DOI 10.1177/2325958219826596

  View details for PubMedID 30776955

  View details for PubMedCentralID PMC6748529

• Risk of Cervical Intraepithelial Neoplasia 2 or Worse by Cytology, Human Papillomavirus 16/18, and Colposcopy Impression: A Systematic Review and Meta-analysis. Obstetrics and gynecology Silver, M. I., Andrews, J., Cooper, C. K., Gage, J. C., Gold, M. A., Khan, M. J., Massad, L. S., Parvu, V., Perkins, R. B., Schiffman, M., Smith, K. M., Wentzensen, N. 2018; 132 (3): 725-735

  Abstract

  To calculate pooled risk estimates for combinations of cytology result, human papillomavirus (HPV) 16/18 genotype and colposcopy impression to provide a basis for risk-stratified colposcopy and biopsy practice.A PubMed search was conducted on June 1, 2016, and a ClinicalTrials.gov search was conducted on June 9, 2018, using key words such as "uterine cervical neoplasms," "cervical cancer," "mass screening," "early detection of cancer," and "colposcopy."Eligible studies must have included colposcopic impression and either cytology results or HPV 16/18 partial genotype results as well as a histologic biopsy diagnosis from adult women. Manuscripts were reviewed for the following: cytology, HPV status, and colposcopy impression as well as age, number of women, and number of cervical intraepithelial neoplasia (CIN) 2, CIN 3, and cancer cases. Strata were defined by the various combinations of cytology, genotype, and colposcopic impression.Of 340 abstracts identified, nine were eligible for inclusion. Data were also obtained from three unpublished studies, two of which have since been published. We calculated the risk of CIN 2 or worse and CIN 3 or worse based on cytology, colposcopy, and HPV 16/18 test results. We found similar risk patterns across studies in the lowest risk groups such that risk estimates were similar despite different referral populations and study designs. Women with a normal colposcopy impression (no acetowhitening), less than high-grade squamous intraepithelial lesion cytology, and HPV 16/18-negative were at low risk of prevalent precancer. Women with at least two of the following: high-grade squamous intraepithelial lesion cytology, HPV16- or HPV18-positive, and high-grade colposcopic impression were at highest risk of prevalent precancer.Our results support a risk-based approach to colposcopy and biopsy with modifications of practice at the lowest and highest risk levels.

  View details for DOI 10.1097/AOG.0000000000002812

  View details for PubMedID 30095780

  View details for PubMedCentralID PMC6105396

• In Defense of a Simplified, Practical Colposcopic Terminology. Journal of lower genital tract disease Khan, M. J., Massad, L. S., Huh, W. K., Wentzensen, N. 2018; 22 (3): 233-234

  View details for DOI 10.1097/LGT.0000000000000405

  View details for PubMedID 29794821

• Evidence-Based Consensus Recommendations for Colposcopy Practice for Cervical Cancer Prevention in the United States. Journal of lower genital tract disease Wentzensen, N., Massad, L. S., Mayeaux, E. J., Khan, M. J., Waxman, A. G., Einstein, M. H., Conageski, C., Schiffman, M. H., Gold, M. A., Apgar, B. S., Chelmow, D., Choma, K. K., Darragh, T. M., Gage, J. C., Garcia, F. A., Guido, R. S., Jeronimo, J. A., Liu, A., Mathews, C. A., Mitchell, M. M., Moscicki, A. B., Novetsky, A. P., Papasozomenos, T., Perkins, R. B., Silver, M. I., Smith, K. M., Stier, E. A., Tedeschi, C. A., Werner, C. L., Huh, W. K. 2017; 21 (4): 216-222

  Abstract

  The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of colposcopy and directed biopsy for cervical cancer prevention in the United States (US). The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. An extensive literature review was conducted and supplemented by a systematic review and meta-analysis of unpublished data. In addition, a survey of practicing colposcopists was conducted to assess current colposcopy practice in the US. Recommendations were approved by the working group members, and the final revisions were made based on comments received from the public. The recommendations cover terminology, risk-based colposcopy, colposcopy procedures, and colposcopy adjuncts. The ASCCP Colposcopy Standards recommendations are an important step toward raising the standard of colposcopy services delivered to women in the US. Because cervical cancer screening programs are currently undergoing important changes that may affect colposcopy performance, updates to some of the current recommendations may be necessary in the future.

  View details for DOI 10.1097/LGT.0000000000000322

  View details for PubMedID 28953109

• ASCCP Colposcopy Standards: Colposcopy Quality Improvement Recommendations for the United States. Journal of lower genital tract disease Mayeaux, E. J., Novetsky, A. P., Chelmow, D., Garcia, F., Choma, K., Liu, A. H., Papasozomenos, T., Einstein, M. H., Massad, L. S., Wentzensen, N., Waxman, A. G., Conageski, C., Khan, M. J., Huh, W. K. 2017; 21 (4): 242-248

  Abstract

  The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. The ASCCP Quality Improvement Working Group developed evidence-based guidelines to promote best practices and reduce errors in colposcopy and recommended indicators to measure colposcopy quality.The working group performed a systematic review of existing major society and national guidelines and quality indicators. An initial list of potential quality indicators was developed and refined through successive iterative discussions, and draft quality indicators were proposed. The draft recommendations were then reviewed and commented on by the entire Colposcopy Standards Committee, posted online for public comment, and presented at the International Federation for Cervical Pathology and Colposcopy 2017 World Congress for further comment. All comments were considered, additional adjustments made, and the final recommendations approved by the entire Task Force.Eleven quality indicators were selected spanning documentation, biopsy protocols, and time intervals between index screening tests and completion of diagnostic evaluation.The proposed quality indicators are intended to serve as a starting point for quality improvement in colposcopy at a time when colposcopy volume is decreasing and individual procedures are becoming technically more difficult to perform.

  View details for DOI 10.1097/LGT.0000000000000342

  View details for PubMedID 28953113

  View details for PubMedCentralID PMC5678988

• ASCCP Colposcopy Standards: How Do We Perform Colposcopy? Implications for Establishing Standards. Journal of lower genital tract disease Waxman, A. G., Conageski, C., Silver, M. I., Tedeschi, C., Stier, E. A., Apgar, B., Huh, W. K., Wentzensen, N., Massad, L. S., Khan, M. J., Mayeaux, E. J., Einstein, M. H., Schiffman, M. H., Guido, R. S. 2017; 21 (4): 235-241

  Abstract

  The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. Working group 3 defined colposcopy procedure guidelines for minimum and comprehensive colposcopy practice and evaluated the use of colposcopy adjuncts.The working group performed a systematic literature review to identify best practices in colposcopy methodology and to evaluate the use of available colposcopy adjuncts. The literature provided little evidence to support specific elements of the procedure. The working group, therefore, implemented a national survey of current and recent ASCCP members to evaluate common elements of the colposcopy examination. The findings of this survey were modified by expert consensus from the ASCCP Colposcopy Standards Committee members to create guidelines for performing colposcopy. The draft recommendations were posted online for public comment and presented at an open session of the International Federation for Cervical Pathology and Colposcopy 2017 World Congress for further comment. All comments were considered in the development of final recommendations.Minimum and comprehensive colposcopy practice guidelines were developed. These guidelines represent recommended practice in all parts of the examination including the following: precolposcopy evaluation, performing the procedure, documentation of findings, biopsy practice, and postprocedure follow-up.These guidelines are intended to serve as a guide to standardize colposcopy across the United States.

  View details for DOI 10.1097/LGT.0000000000000336

  View details for PubMedID 28953112

  View details for PubMedCentralID PMC5659731

• ASCCP Colposcopy Standards: Risk-Based Colposcopy Practice. Journal of lower genital tract disease Wentzensen, N., Schiffman, M., Silver, M. I., Khan, M. J., Perkins, R. B., Smith, K. M., Gage, J. C., Gold, M. A., Conageski, C., Einstein, M. H., Mayeaux, E. J., Waxman, A. G., Huh, W. K., Massad, L. S. 2017; 21 (4): 230-234

  Abstract

  The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of and approach to colposcopy for cervical cancer prevention in the United States.The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. This article describes the rationale, evidence, and recommendations related to risk-based colposcopy practice.Women referred to colposcopy have a wide range of underlying precancer risk, which can be estimated by referral screening tests including cytology and human papillomavirus testing, in conjunction with the colposcopic impression. Multiple targeted biopsies, at least 2 and up to 4, are recommended to improve detection of prevalent precancers. At the lowest end of the risk spectrum, untargeted biopsies are not recommended, and women with a completely normal colposcopic impression can be observed. At the highest end of the risk spectrum, immediate treatment is an alternative to biopsy confirmation.Assessing the risk of cervical precancer at the colposcopy visit allows for modification of colposcopy procedures consistent with a woman's risk. Implementation of these recommendations is expected to lead to improved detection of cervical precancers at colposcopy, while providing more reassurance of negative colposcopy results.

  View details for DOI 10.1097/LGT.0000000000000334

  View details for PubMedID 28953111

• ASCCP Colposcopy Standards: Role of Colposcopy, Benefits, Potential Harms, and Terminology for Colposcopic Practice. Journal of lower genital tract disease Khan, M. J., Werner, C. L., Darragh, T. M., Guido, R. S., Mathews, C., Moscicki, A. B., Mitchell, M. M., Schiffman, M., Wentzensen, N., Massad, L. S., Mayeaux, E. J., Waxman, A. G., Conageski, C., Einstein, M. H., Huh, W. K. 2017; 21 (4): 223-229

  Abstract

  The American Society for Colposcopy and Cervical Pathology Colposcopy Standards address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. Working Group 1 was tasked with defining the role of colposcopy, describing benefits and potential harms, and developing an official terminology.A systematic literature review was performed. A national survey of American Society for Colposcopy and Cervical Pathology members provided input on current terminology use. The 2011 International Federation for Cervical Pathology and Colposcopy terminology was used as a template and modified to fit colposcopic practice in the United States. For areas without data, expert consensus guided the recommendation. Draft recommendations were posted online for public comment and presented at an open session of the 2017 International Federation for Cervical Pathology and Colposcopy World Congress for further comment. All comments were considered for the final version.Colposcopy is used in the evaluation of abnormal or inconclusive cervical cancer screening tests. Colposcopy aids the identification of cervical precancers that can be treated, and it allows for conservative management of abnormalities unlikely to progress. The potential harms of colposcopy include pain, psychological distress, and adverse effects of the procedure. A comprehensive colposcopy examination should include documentation of cervix visibility, squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), lesion(s) visibility, size and location of lesions, vascular changes, other features of lesion(s), and colposcopic impression. Minimum criteria for reporting include squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), and colposcopic impression.A recommended terminology for use in US colposcopic practice was developed, with comprehensive and minimal criteria for reporting.

  View details for DOI 10.1097/LGT.0000000000000338

  View details for PubMedID 28953110

• Preparing for the Next Round of ASCCP-Sponsored Cervical Screening and Management Guidelines. Journal of lower genital tract disease Schiffman, M., Wentzensen, N., Khan, M. J., Castle, P. E., Chelmow, D., Huh, W. K., Moscicki, A. B., Stockdale, C. K., Darragh, T. M., Silver, M., Guido, R. S. 2017; 21 (2): 87-90

  View details for DOI 10.1097/LGT.0000000000000300

  View details for PubMedID 28244885

  View details for PubMedCentralID PMC5365374

• Genotyping for Human Papillomavirus Types 16 and 18 in Women With Minor Cervical Lesions: A Systematic Review and Meta-analysis. Annals of internal medicine Arbyn, M., Xu, L., Verdoodt, F., Cuzick, J., Szarewski, A., Belinson, J. L., Wentzensen, N., Gage, J. C., Khan, M. J. 2017; 166 (2): 118-127

  Abstract

  High-risk human papillomavirus (hrHPV) testing to triage women with minor cervical lesions generates many referrals.To evaluate the accuracy of genotyping for HPV types 16 and 18 and its utility as a second triage step after hrHPV testing in women with minor cervical lesions.Searches of 4 bibliographic databases, without language restrictions, from 1 January 1999 to 1 February 2016.Studies involving women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL) who were triaged with tests for hrHPV and HPV 16/18 to find cervical intraepithelial neoplasia (grade ≥2 [CIN2+] or grade ≥3 [CIN3+]).Independent study selection, extraction of data, and quality assessment by 2 reviewers.Twenty-four moderate- to good-quality studies involving 8587 women with ASC-US and 5284 with LSIL were found. The pooled sensitivity of HPV 16/18 genotyping for CIN3+ was about 70% for women with either ASC-US or LSIL. The pooled specificity (with a threshold of grade <2 CIN) was 83% (95% CI, 80% to 86%) for women with ASC-US and 76% (CI, 74% to 79%) for those with LSIL. The average risk for CIN3+ was 17% and 19% in HPV 16/18-positive women with ASC-US and LSIL, respectively, and was 5% in hrHPV-positive but HPV 16/18-negative women with either ASC-US or LSIL.Methodological and technical heterogeneity among studies; insufficient data to assess accuracy of separate assays.Testing for HPV 16/18 to triage women with minor abnormal cytology is poorly sensitive but may be useful as a second triage test after hrHPV testing, with direct referral if the woman is positive for HPV 16/18. Whether colposcopy or repeated testing is recommended for hrHPV-positive but HPV 16/18-negative women depends on local decision thresholds that can be derived from pretest-posttest probability plots.7th Framework Programme of the European Commission.

  View details for DOI 10.7326/M15-2735

  View details for PubMedID 27842420

• A common clinical dilemma: Management of abnormal vaginal cytology and human papillomavirus test results. Gynecologic oncology Khan, M. J., Massad, L. S., Kinney, W., Gold, M. A., Mayeaux, E. J., Darragh, T. M., Castle, P. E., Chelmow, D., Lawson, H. W., Huh, W. K. 2016; 141 (2): 364-370

  Abstract

  Vaginal cancer is an uncommon cancer of the lower genital tract, and standardized screening is not recommended. Risk factors for vaginal cancer include a history of other lower genital tract neoplasia or cancer, smoking, immunosuppression, and exposure to diethylstilbestrol in utero. Although cervical cancer screening after total hysterectomy for benign disease is not recommended, many women inappropriately undergo vaginal cytology and/or human papillomavirus (hrHPV) tests, and clinicians are faced with managing their abnormal results. Our objective is to review the literature on vaginal cytology and hrHPV testing and to develop guidance for the management of abnormal vaginal screening tests.An electronic search of the PubMed database through 2015 was performed. Articles describing vaginal cytology or vaginal hrHPV testing were reviewed, and diagnostic accuracy of these tests when available was noted.The available literature was too limited to develop evidence-based recommendations for managing abnormal vaginal cytology and hrHPV screening tests. However, the data did show that 1) the risk of vaginal cancer in women after hysterectomy is extremely low, justifying the recommendation against routine screening, and 2) in women for whom surveillance is recommended, e.g. women post-treatment for cervical precancer or cancer, hrHPV testing may be useful in identification of vaginal cancer precursors.Vaginal cancer is rare, and asymptomatic low-risk women should not be screened. An algorithm based on expert opinion is proposed for managing women with abnormal vaginal test results.

  View details for DOI 10.1016/j.ygyno.2015.11.023

  View details for PubMedID 26915529

  View details for PubMedCentralID PMC4977828

• Evaluation of Human Papillomavirus as a Risk Factor for Preterm Birth or Pregnancy-Related Hypertension. Obstetrics and gynecology Subramaniam, A., Lees, B. F., Becker, D. A., Tang, Y., Khan, M. J., Edwards, R. K. 2016; 127 (2): 233-40

  Abstract

  To compare rates of preterm birth and pregnancy-related hypertension in women with and without human papillomavirus (HPV) infection.We performed a retrospective cohort study of all women delivered at our institution in 2013 who had cervical cancer screening test results within 3 years before delivery. Patients were excluded if they had prior procedure(s) for cervical dysplasia other than biopsy. There were two primary outcomes: preterm birth (less than 37 weeks of gestation) and pregnancy-related hypertension (gestational hypertension, preeclampsia, or eclampsia). Multivariable logistic regression was performed to adjust for confounders including demographic variables, diabetes, prior preterm birth, chronic hypertension, and other genital infections. Assuming a 10% prevalence of HPV, a rate of 12% in the HPV-negative group for both preterm birth and pregnancy-related hypertension, α of 0.05, and β of 0.2, we needed 2,207 patients to detect a 60% increase in the rate of either outcome in the HPV-positive group.A total of 3,958 patients delivered in 2013, of whom 2,321 met eligibility criteria, 242 (10.4%) of whom were HPV-positive and 2,079 (89.2%) of whom were HPV-negative. In multivariate analyses, the rate of preterm birth was not significantly different between HPV-positive and HPV-negative women (16.5% compared with 12.2%, adjusted odds ratio [OR] 1.3, 95% confidence interval [CI] 0.9-1.9); rates of pregnancy-related hypertension also were not significantly different between HPV-positive and HPV-negative women (17.0% compared with 16.4%, adjusted OR 1.0, 95% CI 0.7-1.5).Maternal HPV infection is not an independent risk factor for preterm birth or pregnancy-related hypertension.

  View details for DOI 10.1097/AOG.0000000000001247

  View details for PubMedID 26942348

• Screening for Anal Cancer in Women. Journal of lower genital tract disease Moscicki, A., Darragh, T. M., Berry-Lawhorn, J. M., Roberts, J. M., Khan, M. J., Boardman, L. A., Chiao, E., Einstein, M. H., Goldstone, S. E., Jay, N., Likes, W. M., Stier, E. A., Welton, M. L., Wiley, D. J., Palefsky, J. M. 2015; 19 (3): S26-41

  Abstract

  The incidence of anal cancer is higher in women than men in the general population and has been increasing for several decades. Similar to cervical cancer, most anal cancers are associated with human papillomavirus (HPV), and it is believed that anal cancers are preceded by anal high-grade squamous intraepithelial lesions (HSIL). Our goals were to summarize the literature on anal cancer, HSIL, and HPV infection in women and to provide screening recommendations in women.A group of experts convened by the American Society for Colposcopy and Cervical Pathology and the International Anal Neoplasia Society reviewed the literature on anal HPV infection, anal SIL, and anal cancer in women.Anal HPV infection is common in women but is relatively transient in most. The risk of anal HSIL and cancer varies considerably by risk group, with human immunodeficiency virus-infected women and those with a history of lower genital tract neoplasia at highest risk compared with the general population.While there are no data yet to demonstrate that identification and treatment of anal HSIL leads to reduced risk of anal cancer, women in groups at the highest risk should be queried for anal cancer symptoms and required to have digital anorectal examinations to detect anal cancers. Human immunodeficiency virus-infected women and women with lower genital tract neoplasia may be considered for screening with anal cytology with triage to treatment if HSIL is diagnosed. Healthy women with no known risk factors or anal cancer symptoms do not need to be routinely screened for anal cancer or anal HSIL.

  View details for DOI 10.1097/LGT.0000000000000117

  View details for PubMedID 26103446

  View details for PubMedCentralID PMC4479419

• Does treatment for cervical and vulvar dysplasia impact women's sexual health? American journal of obstetrics and gynecology Cendejas, B. R., Smith-McCune, K. K., Khan, M. J. 2015; 212 (3): 291-7

  Abstract

  Human papillomavirus-associated disease represents an immense public health burden worldwide. Persistent human papillomavirus infection can lead to the development of cervical dysplasia and vulvar dysplasia, both of which have been increasing in incidence in women in recent years. Numerous studies have focused on methods for screening and diagnosis of cervical dysplasia, but few have looked at the effects of treatment on women's psychological and sexual health. Even fewer studies have addressed these issues in women with vulvar dysplasia. The aim of this article was to provide a comprehensive review of the existing evidence concerning the impact of therapy for cervical and vulvar precancers on women's sexual function and sexual relationships. We performed a search of the medical literature for the time period up to and including August 2013 on PubMed. The findings from a limited number of studies to date indicate that psychosexual vulnerability increases after diagnosis and treatment of both cervical and vulvar dysplasia. More in-depth research is needed to better understand the effects of different treatment modalities on women's sexual health and relationships during and following treatment.

  View details for DOI 10.1016/j.ajog.2014.05.039

  View details for PubMedID 24881827

  View details for PubMedCentralID PMC4247814

• Treatment of cervical precancers: back to basics. Obstetrics and gynecology Khan, M. J., Smith-McCune, K. K. 2014; 123 (6): 1339-43

  Abstract

  Both ablative (cervical cryotherapy, laser ablation) and excisional methods (loop electrosurgical excision procedure, cold knife conization) can be effective at treating cervical precancer. Excisional procedures are associated with adverse obstetric outcomes including preterm delivery and perinatal mortality with the depth of excision potentially contributing to the adverse outcomes. Ablative therapies are now used much less commonly than loop electrosurgical excision procedure but have less of an effect on adverse obstetric outcomes and hence are effective alternatives for treating cervical precancer in reproductive-aged women. Morphometric data indicate that the vast majority of precancerous lesions are less than 5 mm deep, suggesting that treatments that reach 6-7 mm below the epithelium are adequate in women with satisfactory colposcopy. Cone biopsies, "top-hat" loop electrosurgical excision procedures, or the use of loop electrodes greater than 10 mm are therefore unnecessary for the majority of reproductive-aged women and increase risk of adverse obstetric outcomes. New consensus guidelines allow observation instead of treatment in appropriately selected young women. Until the association of excisional methods with adverse obstetric outcomes is clarified with more data, ablative methods should be revitalized and used by health care providers in appropriately selected patients. Treatment should be individualized based on patient's age, fertility desires, and colpopathologic findings.

  View details for DOI 10.1097/AOG.0000000000000287

  View details for PubMedID 24807323

  View details for PubMedCentralID PMC4077778

• Nongenital human papillomavirus disease. Obstetrics and gynecology clinics of North America Mayeaux, E. J., Khan, M. J. 2013; 40 (2): 317-37

  Abstract

  Human papillomavirus (HPV) is the most common viral cause of cancer, and is responsible for 5% of cancers worldwide. Following demonstration of the causative link between HPV and cervical cancer, HPV has been shown to be associated with several anogenital malignancies and with oral pharyngeal cancers. HPV-related anal and oral pharyngeal disease is rising in incidence and includes anal warts and neoplasia, recurrent respiratory papillomatosis, and oral pharyngeal neoplasia. This article presents an overview of the epidemiology, clinical manifestations, diagnosis, and treatment of nongenital HPV-related disease.

  View details for DOI 10.1016/j.ogc.2013.02.006

  View details for PubMedID 23732034

• Diagnostic utility of endocervical curettage in women undergoing colposcopy for equivocal or low-grade cytologic abnormalities. Obstetrics and gynecology Solomon, D., Stoler, M., Jeronimo, J., Khan, M., Castle, P., Schiffman, M. 2007; 110 (2 Pt 1): 288-95

  Abstract

  To estimate the diagnostic yield of endocervical curettage (ECC) when performed as part of a colposcopic procedure in the multicenter ASCUS-LSIL Triage Study (ALTS), a randomized trial of management strategies for women with equivocal or mildly abnormal cytology.A total of 1,119 women in ALTS had colposcopic examinations that included an ECC performed at the discretion of the colposcopist. We compared the results of ECC and concurrent cervical colposcopic evaluation, with or without biopsy, in prediction of final histopathologic diagnosis. This was defined as the worst histopathologic result from that colposcopy or any subsequent procedure during 2 years of follow-up.Overall, 3.7% of ECCs yielded a diagnostic abnormality of cervical intraepithelial neoplasia (CIN) 2+ compared with 21.7% of colposcopically directed biopsies. In women ultimately found to have CIN 2+ in the trial, the overall sensitivity of colposcopically directed biopsy was 72.5%, compared with 12.2% for ECC. In women under 40, the marginal contribution of ECC, independently of biopsy, was only 2.2%. By contrast, among women 40 and older, the sensitivity of biopsy dropped while the sensitivity of ECC improved, resulting in 13.0% increased detection with ECC, independently of biopsy. However, in women 40 and older, the combined sensitivity of ECC and biopsy was only 47.8% for a single colposcopy procedure.As an ancillary diagnostic technique to colposcopically directed biopsy, ECC is of questionable value in younger women. However, in women aged 40 and older, the sensitivity of colposcopic biopsy decreased and the sensitivity of ECC increased. Thus, ECC may be useful in older women undergoing colposcopy for equivocal or mildly abnormal cytology.

  View details for DOI 10.1097/01.AOG.0000270154.69879.09

  View details for PubMedID 17666602

• Accuracy of human papillomavirus testing in primary screening of cervical neoplasia: results from a multicenter study in India. International journal of cancer Khan, M. J., Schiffman, M., Jeronimo, J. 2005; 116 (5): 830-1

  View details for DOI 10.1002/ijc.21084

  View details for PubMedID 15849748

• The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. Journal of the National Cancer Institute Khan, M. J., Castle, P. E., Lorincz, A. T., Wacholder, S., Sherman, M., Scott, D. R., Rush, B. B., Glass, A. G., Schiffman, M. 2005; 97 (14): 1072-9

  Abstract

  Human papillomavirus (HPV) types 16 and 18 cause 60%-70% of cervical cancer worldwide, and other HPV types cause virtually all remaining cases. Pooled HPV testing for 13 oncogenic types, including HPV16 and 18, is currently used in clinical practice for triage of equivocal cytology and, in conjunction with Pap tests, is an option for general screening among women 30 years of age and older. It is not clear to what extent individual identification of HPV16 or HPV18 as an adjunct to pooled oncogenic HPV testing might effectively identify women at particularly high risk of cervical cancer or its immediate precursor, cervical intraepithelial neoplasia 3 (CIN3).From April 1, 1989, to November 2, 1990, a total of 20 810 women in the Kaiser Permanente health plan in Portland, OR, enrolled in a cohort study of HPV and cervical neoplasia. Women were tested for 13 oncogenic HPV types by Hybrid Capture 2 (HC2), and those women with a positive HC2 test were tested for HPV16 and 18. Enrollment Pap smear interpretation and HPV test results were linked to histologically confirmed CIN3 and cervical cancer (> or = CIN3) occurring during 10 years of cytologic follow-up. We calculated cumulative incidence rates with 95% confidence intervals for each interval up to 122 months using Kaplan-Meier methods.The 10-year cumulative incidence rates of > or = CIN3 were 17.2% (95% confidence interval [CI] = 11.5% to 22.9%) among HPV16+ women and 13.6% (95% CI = 3.6% to 23.7%) among HPV18+ (HPV16-) women, but only 3.0% (95% CI = 1.9% to 4.2%) among HC2+ women negative for HPV16 or HPV18. The 10-year cumulative incidence among HC2- women was 0.8% (95% CI = 0.6% to 1.1%). A subanalysis among women 30 years of age and older with normal cytology at enrollment strengthened the observed risk differences.HPV screening that distinguishes HPV16 and HPV18 from other oncogenic HPV types may identify women at the greatest risk of > or = CIN3 and may permit less aggressive management of other women with oncogenic HPV infections.

  View details for DOI 10.1093/jnci/dji187

  View details for PubMedID 16030305

• Socioeconomic status and the risk of cervical intraepithelial neoplasia grade 3 among oncogenic human papillomavirus DNA-positive women with equivocal or mildly abnormal cytology. Cancer Khan, M. J., Partridge, E. E., Wang, S. S., Schiffman, M. 2005; 104 (1): 61-70

  Abstract

  Low socioeconomic status (SES) is a reported risk factor for cervical carcinoma, but few studies have taken into account adequately the possibly confounding effects of oncogenic human papillomavirus (HPV) infection as well as access to screening and subsequent treatment.Women (n = 5060 women) with a mean age of 27.5 years and with equivocal or mild cytologic cervical abnormalities were enrolled in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion (ASCUS-LSIL) Triage Study (ALTS), a clinical trial that evaluated management strategies. The women were seen every 6 months for 2 years. The enrollment questionnaire assessed three indicators of SES: race/ethnicity, education, and source of payment for medical care. Multivariate logistic regression models were used to identify predictors of oncogenic HPV DNA positivity at enrollment and to assess associations between the SES indicators and risk of cervical intraepithelial neoplasia grade 3 (precancer) and carcinoma (> or = CIN3) identified throughout the study (n = 506 women) among oncogenic HPV-positive women (n = 3133 women).SES indicators were not associated significantly with oncogenic HPV infection after adjustment for age at enrollment, recent and lifetime number of sexual partners, study center, and smoking history. Among women with oncogenic HPV, the risk of > or = CIN3 increased with decreasing education (less than high school education: odds ratio [OR], 2.4; 95% confidence interval [95%CI], 1.5-3.7 vs. completed college). Black women (OR, 0.5; 95%CI, 0.4-0.7) and white/Hispanic women (OR, 0.4; 95%CI, 0.2-0.8) were at decreased risk for > or = CIN3 compared with white/non-Hispanic women. The source of payment for medical care was not associated with risk.Factors associated with lower SES, such as low education, may serve as a surrogate for unknown factors that influence progression to > or = CIN3 among women with oncogenic HPV infection. In this controlled setting with equalized follow-up and treatment, the decreased risk of > or = CIN3 associated with black and white/Hispanic race/ethnicity could be further examined. Ongoing efforts should emphasize methods for equalizing screening and follow-up among women of varying SES, regardless of race or ethnicity.

  View details for DOI 10.1002/cncr.21129

  View details for PubMedID 15889450

• Re: Munoz et al., "Against which human papillomavirus types shall we vaccinate and screen? The international perspective." Int J Cancer 2004;111:278-85. International journal of cancer Khan, M. J., Herrero, R., Schiffman, M. 2005; 115 (4): 670

  View details for DOI 10.1002/ijc.20947

  View details for PubMedID 15704103

• Does the interval between papanicolaou tests influence the quality of cytology? Cancer Jeronimo, J., Khan, M. J., Schiffman, M., Solomon, D. 2005; 105 (3): 133-8

  Abstract

  It is commonly believed that the sensitivity of Papanicolaou (Pap) tests decreases with a short interval between cytology samplings. To the authors' knowledge, there is only limited evidence to support this belief.For 5055 women in the Atypical Squamous Cells of Undetermined Significance (ASCUS)-Low Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS), the Pap interval was defined as the number of days between the referral Pap smear demonstrating ASCUS or LSIL ("first cytology") and the enrollment liquid-based ("repeat") cytology. The authors investigated the influence of the interval between Pap smears on repeat cytology by examining percentages of abnormal findings, cellularity, and test sensitivity among women diagnosed with histologic grade 3 cervical intraepithelial neoplasia (CIN3) during the 2-year course of the ALTS. In addition, because human papillomavirus (HPV) DNA adjunct testing is now performed, the authors evaluated HPV viral load, which was assayed using residual liquid cytology specimens, in women with CIN3.The Pap interval ranged from 8-30 days in 763 women, 31-60 days in 2317 women, 61-90 days in 1090 women, 91-120 days in 491 women, and 121-184 days in 394 women (mean of 61.3 days; standard deviation of 34 days). Repeat cytologic interpretations of unsatisfactory findings, ASCUS, and high-grade squamous intraepithelial lesion (HSIL) did not appear to vary among the Pap interval groups. However, low-grade cytologic regression occurred with an increasing Pap interval; negative cytology increased from 28.3% (8-30 days) to 41.6% (121-184 days) (P < 0.0001) whereas LSIL cytology decreased (P trend = 0.002). The approximate cellularity of the samples was slightly better in the interval group of 8-30 days (P trend = 0.04). Among women with CIN3, the repeat test sensitivity at a threshold of ASCUS or greater and the HPV DNA viral load was not found to vary by Pap interval (P trend = 0.80 and P trend = 0.36, respectively).The authors concluded that a short Pap interval (range, 15-120 days) does not significantly affect the quality of liquid-based repeat cytology, nor the viral load tested from a residual liquid-based specimen.

  View details for DOI 10.1002/cncr.21065

  View details for PubMedID 15822121

• A study of the impact of adding HPV types to cervical cancer screening and triage tests. Journal of the National Cancer Institute Schiffman, M., Khan, M. J., Solomon, D., Herrero, R., Wacholder, S., Hildesheim, A., Rodriguez, A. C., Bratti, M. C., Wheeler, C. M., Burk, R. D. 2005; 97 (2): 147-50

  Abstract

  Use of human papillomavirus (HPV) testing in cervical cancer prevention is increasing rapidly. A DNA test for 13 HPV types that can cause cervical cancer is approved in the United States for co-screening with cytology of women >or=30 years old and for triage of women of all ages with equivocal cytology. However, most infections with HPV are benign. We evaluated trade-offs between specificity and sensitivity for approximately 40 HPV types in predicting cervical intraepithelial neoplasia 3 and cancer in two prospective studies: a population-based screening study that followed 6196 women aged 30-94 years from Costa Rica for 7 years and a triage study that followed 3363 women aged 18-90 years with equivocal cytology in four U.S. centers for 2 years. For both screening and triage, testing for more than about 10 HPV types decreased specificity more than it increased sensitivity. The minimal increases in sensitivity and in negative predictive value achieved by adding HPV types to DNA tests must be weighed against the projected burden to thousands of women falsely labeled as being at high risk of cervical cancer.

  View details for DOI 10.1093/jnci/dji014

  View details for PubMedID 15657345