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Biopsy Practice



Regardless of skill, performing more biopsies increases the sensitivity of colposcopy.                                                                       Pretorius RG, Belinson JL, Burchette RJ, Hu S, Zhang X, Qiao YL. J Low Genit Tract Dis. 2011 Jul;15(3):180-8.

Performing more cervical biopsies and endocervical curettage routinely, even if the biopsies are randomly chosen (normal appearing tissue on colposcopy improves the detection of CIN 3+.


Number of cervical biopsies and sensitivity of colposcopy                                                                                                                           Gage JC, Hanson VW, Abbey K, Dippery S, Gardner S, Kubota J, Schiffman M, Solomon D, Jeronimo J; ASCUS LSIL Triage Study (ALTS) Group. Obstet Gynecol. 2006 Aug;108(2):264-72.

Regardless of medical training or background, conventional colposcopic biopsy practice only detects 66.7% of high grade (CIN 3+) dysplasia. The sensitivity improves when 2 or more biopsies are performed during colposcopy.


Utility of Random Cervical Biopsy and Endocervical Curettage in a Low-Risk Population.                                                                                      Pretorius RG, Belinson JL, Azizi F, Peterson PC, Belinson S. J Low Genit Tract Dis. 2012 May 22.
Approximately 21% of CIN 3+ was detected when random biopsies were performed in addition to customary directed biopsy during colposcopy.


Colposcopy to evaluate abnormal cervical cytology in 2008.                                                                                                                                                                        Chase DM, Kalouyan M, DiSaia PJ.Am J Obstet Gynecol. 2009 May;200(5):472-80. Review.
Liberal use of biopsy in colposcopy and optical technologies that enhance the visualization of lesions during colposcopy will improve the detection of cervical cancer precursors. 

Validity of sampling error as a cause of noncorrelation.                                                                                                                                                                          Hearp ML, Locante AM, Ben-Rubin M, Dietrich R, David O. Cancer. 2007 Oct 25;111(5):275-9.

Approximately half of all biopsy proven high grade CIN is missed during colposcopy biopsy, when excisional LEEP or cone biopsy specimens are used for comparison. The authors conclude biopsy sampling error, due to mis-targeting or other factors are responsible.

 Relevance of random biopsy of the transformation zone when colposcopy is negative.                                                                                                                               Huh WK, Sideri M, Stoler M, Zhang G, Feldman R, Behrens CM.  Obset Gynecol 2014 Oct;124(4):670-8.

A single random biopsy in the ATHENA tiral in patients with negative colposocpy (no lesions visualized), especially when the patient was HPV 16 or HPV 18 positive significantly increased the detection of CIN 2 or higher grade abnormalities.  This post-hoc analysis of a population of 47,000 women undergoing cytology and HPV genotyping recommends the random biopsy practice  in women who had no lesions visualized at colposcopy.

Excellent review on this article and also Wentsensen N, Walker JL, Gold MA, et al. Multiple biopsies and detection of cervical cancer precursors at colposcopy [published online ahead of print November 24, 2014]. J Clin Oncol. pii:JCO.2014.55.9948. at

 2015 Jan 1;33(1):83-9. doi: 10.1200/JCO.2014.55.9948. Epub 2014 Nov 24.

Multiple biopsies and detection of cervical cancer precursors at colposcopy.

The sensitivity of colposcopy in 680 cases study for the detection of high grade precursors increased when biopsies were obtained from all
visible lesions, regardless of the patient characteristics.  The yield from biopsy of normal appearing cervical epithelium was less impressive, with only 2%  of the high grade precursors being discovered by this practice.  The authors recommend this practice of liberal colposcopic directed lesional biopsy.
 2010 Oct;203(4):321.e1-6. doi: 10.1016/j.ajog.2010.05.033. Epub 2010 Jul 14.

Diagnostic accuracy of guided cervical biopsies: a prospective multicenter study comparing the histopathology of simultaneous biopsy and cone specimen.

In a large prospective multicenter trail, usual cervical biopsy practice under-estimated the severity of neoplastic grade of lesions on the cervix in patients who subsequently underwent cone/excisional biopsy procedures.  There were 4888 biopsies performed in 244 cases where the colposcopic punch biopsy-evidence  workup underestrimate the highest grade dypslasia in 46.7% of cases.

 2016 Nov;95(11):1258-1263. doi: 10.1111/aogs.13009.

Colposcopy and additive diagnostic value of biopsies from colposcopy-negative areas to detect cervical dysplasia.

Nearly 40% more CIN 2+ was detected when random biopsy via 4 quadrant biopsy approach was utilized over biopsy of colposcopically visibly abnormal areas. 
 2014 Nov;135(2):201-7. doi: 10.1016/j.ygyno.2014.08.040. Epub 2014 Sep 7.

The increased detection of cervical intraepithelial neoplasia when using a second biopsy at colposcopy.

Taking a second lesional biopsy from an acetowhitened area of the cervix improves the detection of CIN 2+ during colposcopy.
 2017 Apr;96(17):e6689. doi: 10.1097/MD.0000000000006689                                                                                                                                   Pooled analysis on the necessity of random 4-quadrant cervical biopsies and endocervical curettage in women with positive screening but negative colposcopy.                                                                                                          Hu SY1Zhang WHLi SMLi NHuang MNPan QJZhang XHan YZhao FHChen WQiao YL.
 Our paper aims to determine the indications for random biopsies and ECC among these screened positive women.Three thousand two hundred thirteen women with any positive screening test result but negative colposcopy, who received random 4-quadrantbiopsies, were pooled from 17 population-based cervical cancer screening studies done in China from 1999 to 2008. The detection rates of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN grade 3 or worse (CIN3+) stratified by cytology and high-risk human papillomavirus (HR-HPV) status were assessed, as well as the false negative rates for CIN2+ and CIN3+ by random biopsies without ECC.Compared with women with negative cytology and positive HR-HPV, those with atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (ASC-US/LSIL) and negative HR-HPV had the equivalent lower risks of CIN2+ and CIN3+, but ascending risks were observed in the groups of ASC-US/LSIL and positive HR-HPV, and atypical glandular cells/atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion or worse (AGC/ASC-H/HSIL+)If random biopsies were only taken without ECC, 9.3% of CIN2+ and 18.5% of CIN3+ would have been missed.For women with any positive screening but negative colposcopy, in areas with good cytological infrastructure, it was necessary to perform random biopsies plus ECC on those with cytological ASC-US/LSIL and positive HR-HPV, AGC, ASC-H, or HSIL+. In contrast, those with other results should be followed up.
Clin Oncol. 2015 Jan 1;33(1):83-9. doi: 10.1200/JCO.2014.55.9948. Epub 2014 Nov 24.
Multiple biospes and detection of cervical cancer precursors at colposcopy.
Wentzensen N, Walker JL, Gold MA, Smith KM, Zuna RE, Mathews C, Dunn ST, Zhang R, Moxley K, Bishop E, Tenney M, Nugent E, Graubard BI, Wacholder S, Schiffman M.