Adjunct p16INK4a Immunohistochemistry Aids the Detection of High-Grade Squamous Intraepithelial Lesions in Endocervical Curettage Specimens

Shah, Akeesha A.; Jeffus, Susanne K.; Zhao, Zimin; Stoler, Mark H.; Stelow, Edward B.

doi:10.1309/ajcpdxd41ylvazzn

Cited by 7 publications

(4 citation statements)

References 25 publications

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“…From a practical perspective, this suggests that the most important thing clinicians and pathologists can do to appropriately triage patients is to sample robustly (ie, take multiple biopsies) and, when ambiguity exists on H&E, cut level sections liberally and only when necessary selectively use biomarkers to help adjudicate the diagnosis. 23 …”

Section: Discussionmentioning

confidence: 99%

Risk Stratification By p16 Immunostaining of CIN1 Biopsies

Mills

Paquette

Castle

et al. 2015

American Journal of Surgical Pathology

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Previous studies of p16 immunohistochemistry (IHC) on CIN1 have suggested the likely utility of p16 in stratification of women at risk for subsequent CIN2/3. But those studies had limitations in statistical power, histologic diagnosis, and disease ascertainment. We conducted a retrospective study of p16 IHC on adjudicated CIN1 tissue diagnosed in young women participating in the placebo arm of the quadrivalent human papillomavirus (HPV) vaccine trials. Tissue sections were stained with p16 IHC and hematoxylin and eosin. p16 IHC was scored using LAST criteria, and hematoxylin and eosin-stained sections were reviewed for concordance with the adjudicated diagnosis. p16 IHC, antecedent high-grade cytology, review diagnosis, and HPV16 detection were assessed as independent risk factors for subsequent CIN2/3. Five hundred twenty-four patients with CIN1 biopsies and complete data were identified, 63 (12.0%) of whom developed CIN2/3 in follow-up. p16 positivity (P=0.06), review diagnosis of CIN2/3 (P=0.04), HPV16 positivity (P=0.01), and antecedent high-grade cytology (P=0.02) were (marginally) associated with CIN2/3. In a logistic regression model, the associations with CIN2/3 (vs. other), expressed as odds ratios (95% confidence intervals), were 1.6 (0.91-2.8) for p16, 2.0 (1.0-3.7) for HPV16, and 2.2 (1.1-2.4) for antecedent high-grade cytology. The mean risks for CIN2/3 estimated from the model ranged from 7.6% for negative for all markers to 36.3% for positive for all 3 markers. p16 IHC does not risk stratify CIN1 patients in a manner that would alter recommended management for CIN1. This reinforces the LAST recommendations that p16 should only be used selectively for problematic scenarios, such as CIN2 because of its inherent lack of reproducibility, cases in which one is struggling between CIN1 and CIN2, and benign mimics of CIN3.

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Section: Discussionmentioning

confidence: 99%

Risk Stratification By p16 Immunostaining of CIN1 Biopsies

Mills

Paquette

Castle

et al. 2015

American Journal of Surgical Pathology

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“…Moreover, ECC is hard to perform in patients with a stenotic cervix or in menopausal women [ 7 ]. The inter-observer agreement of the interpretation of ECC specimens is poor [ 8 , 9 ]. ECC is an uncomfortable procedure and has been rated as a 5.8 (0 to 10) on a visual analog scale by patients in prior studies [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a clinical prediction model for endocervical curettage decision-making in cervical lesions

Luo

Zhang

et al. 2021

BMC Cancer

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Background In the absence of practical and reliable predictors for whether the endocervical curettage (ECC) procedure should be performed, decisions regarding patient selection are usually based on the colposcopists’ clinical judgment instead of evidence. We aimed to develop and validate a practical prediction model that uses available information to reliably estimate the need to perform ECC in patients suspected of having cervical lesions. Methods In this retrospective study, 2088 patients who underwent colposcopy, colposcopically directed biopsy (CDB) and ECC procedures between September 2019 and September 2020 at the Second Hospital of Shanxi Medical University were included. The data were analyzed with univariate and multivariable logistic regression. Least absolute shrinkage and selection operator (LASSO) was used to select predictors for ECC positivity. The ECC prediction model was presented as a nomogram and evaluated in terms of discrimination and calibration. Furthermore, this model was validated internally with cross-validation and bootstrapping. Results Significant trends were found for ECC positivity with increasing age (P = 0.001), menopause (P = 0.003), Human papillomavirus (HPV) status (P < 0.001), severity of ThinPrep Cytological Test (TCT) (P < 0.001), original squamous epithelium ectopia (P = 0.037) and colposcopy impression (P < 0.001) by multivariable logistic regression analysis. The ECC prediction model was developed based on the following predictors: age, menopause, symptom of contact bleeding, severity of TCT, HPV status, cervix visibility, original squamous epithelium ectopia, acetowhite changes and colposcopic impression. This model had satisfactory calibration and good discrimination, with an area under the receiver operator characteristic curve (AUC) of 0.869 (95% confidence interval 0.849 to 0.889). Conclusions A readily applicable clinical prediction model was constructed to reliably estimate the probability of ECC positivity in patients suspicious of having cervical lesions, which may help clinicians make decisions regarding the ECC procedure and possibly prevent adverse effects.

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“…Given this low homogeneity restriction, integrating techniques into ECC may be a viable option to bring clarity to diagnostic classification. Shah et al applied p16/Ki67 dual stain to 58 ECC specimens and diagnosed 18 additional cases of HSIL [ 26 ]. Maximiliano et al attempted to overcome the drawbacks associated with the sparseness of ECC tissue using cell concentration methods, which may be a suitable strategy for qualitative improvement of the sensitivity of ECC and its diagnostic value [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Endocervical curettage for diagnosing high-grade squamous intraepithelial lesions or worse in women with type 3 transformation zone lesions: a retrospective, observational study

Wei

Seery

et al. 2023

BMC Women's Health

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Background This study aimed to assess the value of endocervical curettage (ECC) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+) in women with type 3 transformation zone (TZ3) lesions, and to identify the clinical characteristics of patients with TZ3 lesions who benefit most from ECC. Methods This retrospective, multicenter study included 1,905 women with TZ3 lesions who attended cervical screening in one of seven tertiary hospitals in China between January 2020 and November 2021. All participants had received abnormal results and had been referred to colposcopy. Risk factors were identified through univariate and multifactorial logistic analyses. Results In total, 20.5% (n = 391) of HSIL+ cases with TZ3 lesions had been diagnosed with biopsy and ECC. ECC detected 0.8% (n = 15) HSIL+ cases otherwise missed by biopsy alone. Multivariate analysis identified four factors which influenced detection performance. The probability of detecting HSIL+ with ECC is 2.653 (95% confidence interval [CI] 1.009–6.977) times greater in women aged 40–49 years and 2.545 (95% CI 0.965–6.716) times greater for those aged 50 years and older compared to those younger than 30 years. The probability of ASC-H (atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion) and HSIL cytologies were respectively 2.415 (95% CI 1.213–4.808) and 2.933 (95% CI 1.648–5.220) times higher than for NILM (negative for intraepithelial lesion or malignancy). Women with human papillomavirus 16/18 infections were 2.299 (95% CI 0.942–5.613) times more likely to be HSIL+. Precancerous lesions were 35.884 (95% CI 12.214–105.426) times more likely in women who had high-grade colposcopic impressions compared to those with normal impressions. Conclusions ECC should be performed for patients with ASC-H or HSIL cytologies, human papillomavirus 16/18 infections, and for those with high-grade colposcopic impressions. This will increase the number of HSIL+ cases identified using biopsy by reducing the number of false negatives.

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Adjunct p16INK4a Immunohistochemistry Aids the Detection of High-Grade Squamous Intraepithelial Lesions in Endocervical Curettage Specimens

Abstract: The use of recuts and adjunct p16(INK4a) should be considered when evaluating ECC specimens in high-risk patient populations.

Cited by 7 publications

References 25 publications

Risk Stratification By p16 Immunostaining of CIN1 Biopsies

Risk Stratification By p16 Immunostaining of CIN1 Biopsies

Development and validation of a clinical prediction model for endocervical curettage decision-making in cervical lesions

Endocervical curettage for diagnosing high-grade squamous intraepithelial lesions or worse in women with type 3 transformation zone lesions: a retrospective, observational study

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