Approximately one-third of cervical intraepithelial neoplasia 2 and above can be missed by only biopsying quadrants of the cervix with visible lesions by digital cervicography

Bateman, A.C.

Chibwesha, C.J.

Parham, G.P.

PubMed

Carolina Digital Repository

Minimizing verification bias in cervical cancer screening of HIV-infected womenAllen C. Batemana,b,*, Carla J. Chibweshaa,c, and Groesbeck P. Parhama,c,da Centre for Infectious Disease Research in Zambia, Lusaka, Zambiab Department of Medicine, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAc Department of Obstetrics and Gynecology, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAd University Teaching Hospital, Lusaka, ZambiaSynopsisApproximately one-third of cervical intraepithelial neoplasia 2 and above can be missed by only biopsying quadrants of the cervix with visible lesions by digital cervicography.KeywordsBiopsy; Cervical cancer; HIV; Screening; Verification bias; ZambiaHIV infection is associated with a higher incidence rate of cervical lesions and increased risk of cervical cancer [1]. New cervical cancer screening tests are available or in development, and many biomarkers hold promise for screening. It is important to evaluate the clinical performance characteristics of new screening tests in HIV-infected women, to inform possible introduction in this population. Histopathology is commonly used as the gold standard diagnosis in cervical cancer screening studies; however, verification bias can occur if none or only a subset of screen negatives receives histopathology. Verification bias results in an overestimation of sensitivity and underestimation of specificity of the screening test.After receiving ethical approval from appropriate institutional bodies, 268 HIV-infected women accessing cervical cancer screening in Zambia were enrolled in the study [2]. Each woman provided written informed consent and was screened using cytology and visual © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.*Corresponding author: Allen C. Bateman Plot 5032 Great North Road (P.O. Box 34681), Lusaka, Zambia 10101. Tel: +260 976 492 306; fax: +260 211 242 263. bateman.allen@gmail.com. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Conflict of interestThe authors have no conflicts of interest.NIH Public AccessAuthor ManuscriptInt J Gynaecol Obstet. Author manuscript; available in PMC 2016 March 01.Published in final edited form as:Int J Gynaecol Obstet. 2015 March ; 128(3): 269–270. doi:10.1016/j.ijgo.2014.09.007.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptinspection with acetic acid coupled with digital cervicography (DC) [3]. Women with a lesion identified by DC received a biopsy from an area within the lesion most likely representing the most advanced degree of neoplasia, as well as a random biopsy from a quadrant without a lesion (if such a quadrant was present). Women with no visible lesions by DC received a random biopsy. Cervical disease was more advanced in biopsies from quadrants with visible lesions (Table 1), but approximately one-third of cervical intraepithelial neoplasia 2 and above (CIN2+) were from quadrants without lesions (17/55; 31%), demonstrating that not all lesions are visible by DC. The results were stratified based on if one versus multiple cervical sites were sampled (Table 1). There was more disease in quadrants with visible lesions, but a substantial proportion of disease was identified in quadrants without visible lesions.By obtaining a punch biopsy from cervical quadrants with and without visible lesions we estimated the amount of disease typically missed when biopsies are restricted to visible lesions. Approximately one-third of all CIN2+ were from quadrants without visible lesions, analogous to results by Pretorius et al. [4] who reported that 37% of all CIN2+ lesions in HIV-negative women were from colposcopically normal-appearing areas on the cervix. We recommend that screening studies include systematic sampling for histopathology regardless of the screening result, to minimize verification bias in cervical cancer screening trials.AcknowledgementsThe study was funded by US National Cancer Institute Award 3P30AI027767-19. Investigator support was provided through Fogarty International Center Award R25TW009340 to the UNC Hopkins Morehouse Tulane Fogarty Global Health Fellows Program through a National Cancer Institute supplement, as well as National Cancer Institute Award 1D43CA153784. We acknowledge the support of the UNC Lineberger Cancer Center and the UNC Center for AIDS Research.References1. Denslow SA, Rositch AF, Firnhaber C, Ting J, Smith JS. Incidence and progression of cervical lesions in women with HIV: a systematic global review. Int J STD AIDS. 2014; 25(3):163–77. [PubMed: 24216030] 2. Bateman AC, Parham GP, Sahasrabuddhe VV, Mwanahamuntu MH, Kapambwe S, Katundu K, et al. Clinical performance of digital cervicography and cytology for cervical cancer screening in HIV-infected women in Lusaka, Zambia. J Acquir Immune Defic Syndr. 2014; 67(2):212–5. [PubMed: 24977474] 3. Parham GP, Mwanahamuntu MH, Pfaendler KS, Sahasrabuddhe VV, Myung D, Mkumba G, et al. eC3--a modern telecommunications matrix for cervical cancer prevention in Zambia. J Low Genit Tract Dis. 2010; 14(3):167–73. [PubMed: 20592550] 4. Pretorius RG, Zhang WH, Belinson JL, Huang MN, Wu LY, Zhang X, et al. Colposcopically directed biopsy, random cervical biopsy, and endocervical curettage in the diagnosis of cervical intraepithelial neoplasia II or worse. Am J Obstet Gynecol. 2004; 191(2):430–4. [PubMed: 15343217] Bateman et al. Page 2Int J Gynaecol Obstet. Author manuscript; available in PMC 2016 March 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptBateman et al. Page 3Table 1Histopathology diagnosis from cervical quadrants with or without visible lesions.aHistopathology diagnosisRandom biopsy from cervical quadrants without visible lesionsTargeted biopsy from cervical quadrants with visible lesionsTotal bWomen with no cervical quadrants with visible lesionsWomen with one or more cervical quadrants with visible lesionTotal bWomen with all cervical quadrants occupied by visible lesionsWomen with one or more cervical quadrants without visible lesionBenign113 (52.8)77 (58.3)36 (43.9)41 (30.2)11 (20.4)30 (36.6)CIN184 (39.3)47 (35.6)37 (45.1)57 (41.9)23 (42.6)34 (41.5)CIN210 (4.7)4 (3.0)6 (7.3)17 (12.5)9 (16.7)8 (9.8)CIN34 (1.9)2 (1.5)2 (2.4)19 (14.0)10 (18.5)9 (11.0)Cancer3 (1.4)2 (1.5)1 (1.2)2 (1.5)1 (1.9)1 (1.2)Abbreviation: CIN, cervical intraepithelial neoplasia.a Values are given as number (percentage).b Distribution of biopsy results from cervical quadrants with visible lesions is significantly more advanced than biopsy results from quadrants without visible lesions (P<0.001 by χ2  test).Int J Gynaecol Obstet. Author manuscript; available in PMC 2016 March 01.

Minimizing verification bias in cervical cancer screening of HIV-infected women

http://dx.doi.org/10.1016/j.ijgo.2014.09.007

Minimizing verification bias in cervical cancer screening of HIV-infected women

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