The Diagnostic Utility of p16 Immunostaining in Differentiating Cancer and HSIL from LSIL and Benign in Cervical Cells

Cervical liquid-based cytology plays an important role in the diagnosis of cervical squamous intraepithelial lesion (SIL). However, cytological evaluation alone has a relatively low sensitive. To overcome this problem, HPV DNA testing or HPV DNA combined with cytology has been applied. HPV DNA testing significantly improved the sensitivity, but the specificity is low, especially in cancer and high-grade SIL (HSIL) cases. The aim of this study was to evaluate the diagnostic utility of p16 overexpression in cervical cells of patients with HSIL and cancer. The expression of p16 was detected by immunostaining in liquid-based cells from cervical brushing in 278 patients which including: Cancer ( n = 13), HSIL ( n = 112), low-grade SIL (LSIL) ( n = 45), and Benign ( n = 108). The expression levels of p16 were significantly higher in the cancer and HSIL groups when compared with the LSIL and Benign groups ( P < 0.01). The accurate diagnostic rates of cancer and HSIL were significantly increased by p16 immunostaining plus cytology than that by cytology alone ( P < 0.01). The false negative or false positive of p16 immunostaining occurred with a unicellular pattern. With sensitivity of 96.0% and accuracy of 91.7%, the diagnostic performance of p16 immunostaining was much better than that of cytology alone with sensitivity of 36.0% and accuracy of 70.9% ( P < 0.01). p16 immunostaining in cervical brushing cells may not only be used as an ancillary tool to cytological diagnosis of cervical neoplasia but also help to distinguish HSIL from LSIL and the triage of transient infection.

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Findings to Date From the ASCUS-LSIL Triage Study (ALTS)

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-946-ftdfta ◽

2003 ◽

Vol 127 (8) ◽

pp. 946-949 ◽

Cited By ~ 12

Author(s):

Mark Schiffman ◽

Diane Solomon

Keyword(s):

Intraepithelial Neoplasia ◽

The United States ◽

Alternative Methods ◽

Low Grade ◽

High Grade ◽

Dna Testing ◽

Squamous Intraepithelial Lesion ◽

Hpv Dna ◽

Hpv Dna Testing ◽

Intraepithelial Lesion

Abstract Controversy exists in the United States regarding the proper evaluation and management of low-grade squamous intraepithelial lesion (LSIL) and equivocal (atypical squamous cells of undetermined significance [ASCUS, now ASC-US]) cervical cytologic interpretations. To address this issue, the National Cancer Institute initiated the ASCUS-LSIL Triage Study (ALTS). ALTS is a multicenter, randomized clinical trial designed to evaluate 3 alternative methods of management, namely, immediate colposcopy, cytologic follow-up, and triage by human papillomavirus (HPV) DNA testing. This article summarizes the major findings of ALTS that have been published to date. Patients with ASCUS (n = 3488) or LSIL (n = 1572) were randomly assigned to research arms between November 1996 and December 1998, and were monitored for 2 years. The disease outcome was histologic cervical intraepithelial neoplasia (CIN) 3/cancer. The prevalence of oncogenic HPV was too high to permit effective triage of LSIL using HPV DNA testing by Hybrid Capture 2. However, for the women referred with a cytologic interpretation of ASCUS, HPV triage proved useful, with sensitivity equivalent to immediate colposcopy and a halving of colposcopic referrals. Among older women with ASCUS, HPV testing remained sensitive for detecting CIN 3 and cancer, but the referral percentage was dramatically lower compared to younger women. ALTS yielded insight into the performance of cytology and histopathology; experienced pathologists differed significantly in their interpretations of cervical abnormalities, especially histologic CIN 1 and cytologic ASCUS. Nonetheless, it was possible to distinguish a relatively uncommon type of ASCUS, equivocal for high-grade squamous intraepithelial lesion, that has a high positive predictive value for identifying women with underlying high-grade CIN. Many additional analyses are underway.

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Human Papillomavirus Reporting: Minimizing Patient and Laboratory Risk

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-973-hprmpa ◽

2003 ◽

Vol 127 (8) ◽

pp. 973-977

Author(s):

R. Marshall Austin

Keyword(s):

Human Papillomavirus ◽

False Negative ◽

Pap Test ◽

Initial Assessment ◽

Low Grade ◽

Dna Testing ◽

Predictive Values ◽

Hpv Dna ◽

Hpv Dna Testing ◽

Papillomavirus Dna

Abstract Risk management efforts in the cytology laboratory must address the gap between what can be achieved with medical history's most effective cancer screening test, the Papanicolaou (Pap) test, and even higher entrenched public expectations. Data from the Atypical Squamous Cells of Undetermined Significance (ASCUS)/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS) now provide level I clinical evidence from a large, randomized, controlled, multicenter clinical trial that reflex human papillomavirus (HPV) DNA testing of ASCUS cases is generally the preferred method for initial assessment of the most prevalent category of abnormal Pap interpretation. The proposed combination of HPV DNA testing with cytologic Pap testing, the DNA Pap test, further shows the potential to nearly eliminate false-negative screening results, based on sensitivity and negative predictive values reported in available studies. Human papillomavirus DNA testing also appears to represent a significant enhancement for detection of endocervical adenocarcinomas, which are difficult to detect and prevent. Human papillomavirus DNA testing, when used in conjunction with cervical cytology, can significantly reduce risk to both the patient and the laboratory.

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Is HPV-DNA Testing a Useful Tool in Predicting Low-Grade Squamous Intraepithelial Lesion Outcome? A Retrospective Longitudinal Study

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463201002300130 ◽

2010 ◽

Vol 23 (1) ◽

pp. 317-326 ◽

Cited By ~ 4

Author(s):

R. Zappacosta ◽

D. Caraceni ◽

L. Ciccocioppo ◽

M. Ottaviantonio ◽

F. Conti ◽

...

Keyword(s):

Longitudinal Study ◽

Low Grade ◽

Dna Testing ◽

Squamous Intraepithelial Lesion ◽

Hpv Dna ◽

Hpv Dna Testing ◽

Intraepithelial Lesion

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Characteristics of Apparently False-Negative Digene Hybrid Capture 2 High-Risk HPV DNA Testing

American Journal of Clinical Pathology ◽

10.1309/qejbyt77ymtevj66 ◽

2006 ◽

Vol 125 (2) ◽

pp. 223-228 ◽

Cited By ~ 29

Author(s):

Raid Jastania ◽

William R. Geddie ◽

William Chapman ◽

Scott Boerner

Keyword(s):

High Risk ◽

False Negative ◽

Dna Testing ◽

Hybrid Capture ◽

Hpv Dna ◽

Hpv Dna Testing ◽

Hybrid Capture 2 ◽

High Risk Hpv

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Cervical cytology with a diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H): a follow-up study with corresponding histology and significance of predicting dysplasia by human papillomavirus (HPV) DNA testing

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-013-3015-5 ◽

2013 ◽

Vol 289 (3) ◽

pp. 645-648 ◽

Cited By ~ 9

Author(s):

Syed M. Gilani ◽

Randy Tashjian ◽

Lamia Fathallah

Keyword(s):

Human Papillomavirus ◽

High Grade ◽

Dna Testing ◽

Squamous Intraepithelial Lesion ◽

Hpv Dna ◽

Squamous Cells ◽

Follow Up Study ◽

Hpv Dna Testing ◽

Intraepithelial Lesion

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Colposcopic triage methods for detecting cervical intraepithelial neoplasia grade 3 after cytopathological diagnosis of low-grade squamous intraepithelial lesion: a systematic review on diagnostic tests

Sao Paulo Medical Journal ◽

10.1590/s1516-31802012000100008 ◽

2012 ◽

Vol 130 (1) ◽

pp. 44-52 ◽

Cited By ~ 6

Author(s):

Flávia de Miranda Corrêa ◽

Fábio Bastos Russomano ◽

Caroline Alves de Oliveira

Keyword(s):

Systematic Review ◽

Intraepithelial Neoplasia ◽

Low Grade ◽

Dna Testing ◽

Cervical Intraepithelial Neoplasia Grade ◽

Eligibility Criteria ◽

Hpv Dna ◽

Hpv Dna Testing ◽

Grade 3 ◽

Oncogenic Hpv

CONTEXT AND OBJECTIVE: The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL) requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years) of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3), in order to triage for LSIL. DESIGN AND SETTING: Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved. METHODS: The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) guidelines were used for quality assessment. Qualitative information synthesis was performed. RESULTS: Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6% to 12%. The HPV-DNA positivity rate ranged from 64% to 83%; sensitivity for CIN3 detection ranged from 95.2% to 100%; and specificity was available in two studies (27% and 52%). The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS), was available in two studies (33% and 90.8%); and specificity was available in one study (53%). CONCLUSIONS: Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.

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