Is p16INK4A expression more useful than human papillomavirus test to determine the outcome of atypical squamous cells of undetermined significance-categorized Pap smear? A comparative analysis using abnormal cervical smears with follow-up biopsies

Shin Nieh, Su Feng Chen, Tang Yuan Chu, Hung Cheng Lai, Yaoh Shiang Lin, Earl Fu, Ching H. Gau

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Abstract

Objective. To correlate high-risk human papillomavirus (HR-HPV) viral load to p16INK4A expression in atypical squamous cells of undetermined significance (ASCUS)-categorized Pap smears with follow-up biopsies in order to elucidate their relationships in gynecological pathology. Methods. We studied 66 ASCUS-categorized Pap smears with subsequent follow-up biopsies. HR-HPV viral load was determined by Hybrid Capture II assay from the cervical swab in each ASCUS-diagnosed Pap smear. Both smears and biopsies were immunostained with a primary anti-p16 antibody, clone E6H4, and we analyzed the correlations between HR-HPV viral load in each ASCUS-diagnosed Pap smear and p16 expression of smears with follow-up biopsies. Results. Correlation analyses of the corresponding histological diagnoses from 66 ASCUS-diagnosed Pap smears revealed that 21 (32%) cases had only reactive changes and 45 cases showed cervical intraepithelial neoplasia including LSIL (24 cases, 36%) and HSIL or higher (21 cases, 32%). Tests for HR-HPV viral load revealed 17 (26%) negative cases and 49 (74%) positive cases. Immunostaining showed that 26 cases (39%) were negative and 40 (61%) were positive for p16 expression. Comparative analysis of these two tests indicated consistencies as well as discrepancies. They showed significant differences (P <0.001) between negative p16 expressions of Pap smears with the presence of reactive lesions in follow-up biopsies and HR-HPV viral load. However, no significant difference (P = 0.739 and 0.606) between p16 expression of Pap smears with the presence of LSIL, HSIL or higher in follow-up biopsies and high HR-HPV viral load was found. In addition, there were significant differences (P <0.001) in specificity and positive predictive value, but no significant differences were found in sensitivity (P = 0.606) and negative predictive value (P = 0.062) between p16 immunostaining and HR-HPV viral load. Conclusion. The results indicate that there is a close association between weak or strong p16 expressions in ASCUS-categorized smears with the presence of SILs in follow-up biopsies and positive HR-HPV viral loads. Conversely, there is also a clear association between the lack of p16 expression and the absence of significant lesions in follow-up biopsies, but this is not consistent with a negative HR-HPV viral load. It is concluded that p16 expression is an indicator of pathogenic activity of HR-HPV, which is an objective biomarker for clarification of ASCUS-categorized Pap smears in gynecological cytopathology. Furthermore, through comparative analysis, directly visualized p16 immunostaining on smears appears to be a more effective method than HR-HPV viral load for the detection of reactive changes and LSILs from ASCUS-categorized Pap smears.

Original languageEnglish
Pages (from-to)35-40
Number of pages6
JournalGynecologic Oncology
Volume97
Issue number1
DOIs
Publication statusPublished - Apr 2005
Externally publishedYes

Fingerprint

Papanicolaou Test
Vaginal Smears
Viral Load
Biopsy
Atypical Squamous Cells of the Cervix
Cervical Intraepithelial Neoplasia
Anti-Idiotypic Antibodies
Clone Cells
Biomarkers

Keywords

  • Atypical squamous cells of undetermined significance
  • Immunocytochemical detection
  • p16
  • Papanicolaou smear
  • Viral load, high-risk human papillomavirus

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

@article{62d2027c4071401eb9def3a22a13703f,
title = "Is p16INK4A expression more useful than human papillomavirus test to determine the outcome of atypical squamous cells of undetermined significance-categorized Pap smear? A comparative analysis using abnormal cervical smears with follow-up biopsies",
abstract = "Objective. To correlate high-risk human papillomavirus (HR-HPV) viral load to p16INK4A expression in atypical squamous cells of undetermined significance (ASCUS)-categorized Pap smears with follow-up biopsies in order to elucidate their relationships in gynecological pathology. Methods. We studied 66 ASCUS-categorized Pap smears with subsequent follow-up biopsies. HR-HPV viral load was determined by Hybrid Capture II assay from the cervical swab in each ASCUS-diagnosed Pap smear. Both smears and biopsies were immunostained with a primary anti-p16 antibody, clone E6H4, and we analyzed the correlations between HR-HPV viral load in each ASCUS-diagnosed Pap smear and p16 expression of smears with follow-up biopsies. Results. Correlation analyses of the corresponding histological diagnoses from 66 ASCUS-diagnosed Pap smears revealed that 21 (32{\%}) cases had only reactive changes and 45 cases showed cervical intraepithelial neoplasia including LSIL (24 cases, 36{\%}) and HSIL or higher (21 cases, 32{\%}). Tests for HR-HPV viral load revealed 17 (26{\%}) negative cases and 49 (74{\%}) positive cases. Immunostaining showed that 26 cases (39{\%}) were negative and 40 (61{\%}) were positive for p16 expression. Comparative analysis of these two tests indicated consistencies as well as discrepancies. They showed significant differences (P <0.001) between negative p16 expressions of Pap smears with the presence of reactive lesions in follow-up biopsies and HR-HPV viral load. However, no significant difference (P = 0.739 and 0.606) between p16 expression of Pap smears with the presence of LSIL, HSIL or higher in follow-up biopsies and high HR-HPV viral load was found. In addition, there were significant differences (P <0.001) in specificity and positive predictive value, but no significant differences were found in sensitivity (P = 0.606) and negative predictive value (P = 0.062) between p16 immunostaining and HR-HPV viral load. Conclusion. The results indicate that there is a close association between weak or strong p16 expressions in ASCUS-categorized smears with the presence of SILs in follow-up biopsies and positive HR-HPV viral loads. Conversely, there is also a clear association between the lack of p16 expression and the absence of significant lesions in follow-up biopsies, but this is not consistent with a negative HR-HPV viral load. It is concluded that p16 expression is an indicator of pathogenic activity of HR-HPV, which is an objective biomarker for clarification of ASCUS-categorized Pap smears in gynecological cytopathology. Furthermore, through comparative analysis, directly visualized p16 immunostaining on smears appears to be a more effective method than HR-HPV viral load for the detection of reactive changes and LSILs from ASCUS-categorized Pap smears.",
keywords = "Atypical squamous cells of undetermined significance, Immunocytochemical detection, p16, Papanicolaou smear, Viral load, high-risk human papillomavirus",
author = "Shin Nieh and Chen, {Su Feng} and Chu, {Tang Yuan} and Lai, {Hung Cheng} and Lin, {Yaoh Shiang} and Earl Fu and Gau, {Ching H.}",
year = "2005",
month = "4",
doi = "10.1016/j.ygyno.2004.11.034",
language = "English",
volume = "97",
pages = "35--40",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Is p16INK4A expression more useful than human papillomavirus test to determine the outcome of atypical squamous cells of undetermined significance-categorized Pap smear? A comparative analysis using abnormal cervical smears with follow-up biopsies

AU - Nieh, Shin

AU - Chen, Su Feng

AU - Chu, Tang Yuan

AU - Lai, Hung Cheng

AU - Lin, Yaoh Shiang

AU - Fu, Earl

AU - Gau, Ching H.

PY - 2005/4

Y1 - 2005/4

N2 - Objective. To correlate high-risk human papillomavirus (HR-HPV) viral load to p16INK4A expression in atypical squamous cells of undetermined significance (ASCUS)-categorized Pap smears with follow-up biopsies in order to elucidate their relationships in gynecological pathology. Methods. We studied 66 ASCUS-categorized Pap smears with subsequent follow-up biopsies. HR-HPV viral load was determined by Hybrid Capture II assay from the cervical swab in each ASCUS-diagnosed Pap smear. Both smears and biopsies were immunostained with a primary anti-p16 antibody, clone E6H4, and we analyzed the correlations between HR-HPV viral load in each ASCUS-diagnosed Pap smear and p16 expression of smears with follow-up biopsies. Results. Correlation analyses of the corresponding histological diagnoses from 66 ASCUS-diagnosed Pap smears revealed that 21 (32%) cases had only reactive changes and 45 cases showed cervical intraepithelial neoplasia including LSIL (24 cases, 36%) and HSIL or higher (21 cases, 32%). Tests for HR-HPV viral load revealed 17 (26%) negative cases and 49 (74%) positive cases. Immunostaining showed that 26 cases (39%) were negative and 40 (61%) were positive for p16 expression. Comparative analysis of these two tests indicated consistencies as well as discrepancies. They showed significant differences (P <0.001) between negative p16 expressions of Pap smears with the presence of reactive lesions in follow-up biopsies and HR-HPV viral load. However, no significant difference (P = 0.739 and 0.606) between p16 expression of Pap smears with the presence of LSIL, HSIL or higher in follow-up biopsies and high HR-HPV viral load was found. In addition, there were significant differences (P <0.001) in specificity and positive predictive value, but no significant differences were found in sensitivity (P = 0.606) and negative predictive value (P = 0.062) between p16 immunostaining and HR-HPV viral load. Conclusion. The results indicate that there is a close association between weak or strong p16 expressions in ASCUS-categorized smears with the presence of SILs in follow-up biopsies and positive HR-HPV viral loads. Conversely, there is also a clear association between the lack of p16 expression and the absence of significant lesions in follow-up biopsies, but this is not consistent with a negative HR-HPV viral load. It is concluded that p16 expression is an indicator of pathogenic activity of HR-HPV, which is an objective biomarker for clarification of ASCUS-categorized Pap smears in gynecological cytopathology. Furthermore, through comparative analysis, directly visualized p16 immunostaining on smears appears to be a more effective method than HR-HPV viral load for the detection of reactive changes and LSILs from ASCUS-categorized Pap smears.

AB - Objective. To correlate high-risk human papillomavirus (HR-HPV) viral load to p16INK4A expression in atypical squamous cells of undetermined significance (ASCUS)-categorized Pap smears with follow-up biopsies in order to elucidate their relationships in gynecological pathology. Methods. We studied 66 ASCUS-categorized Pap smears with subsequent follow-up biopsies. HR-HPV viral load was determined by Hybrid Capture II assay from the cervical swab in each ASCUS-diagnosed Pap smear. Both smears and biopsies were immunostained with a primary anti-p16 antibody, clone E6H4, and we analyzed the correlations between HR-HPV viral load in each ASCUS-diagnosed Pap smear and p16 expression of smears with follow-up biopsies. Results. Correlation analyses of the corresponding histological diagnoses from 66 ASCUS-diagnosed Pap smears revealed that 21 (32%) cases had only reactive changes and 45 cases showed cervical intraepithelial neoplasia including LSIL (24 cases, 36%) and HSIL or higher (21 cases, 32%). Tests for HR-HPV viral load revealed 17 (26%) negative cases and 49 (74%) positive cases. Immunostaining showed that 26 cases (39%) were negative and 40 (61%) were positive for p16 expression. Comparative analysis of these two tests indicated consistencies as well as discrepancies. They showed significant differences (P <0.001) between negative p16 expressions of Pap smears with the presence of reactive lesions in follow-up biopsies and HR-HPV viral load. However, no significant difference (P = 0.739 and 0.606) between p16 expression of Pap smears with the presence of LSIL, HSIL or higher in follow-up biopsies and high HR-HPV viral load was found. In addition, there were significant differences (P <0.001) in specificity and positive predictive value, but no significant differences were found in sensitivity (P = 0.606) and negative predictive value (P = 0.062) between p16 immunostaining and HR-HPV viral load. Conclusion. The results indicate that there is a close association between weak or strong p16 expressions in ASCUS-categorized smears with the presence of SILs in follow-up biopsies and positive HR-HPV viral loads. Conversely, there is also a clear association between the lack of p16 expression and the absence of significant lesions in follow-up biopsies, but this is not consistent with a negative HR-HPV viral load. It is concluded that p16 expression is an indicator of pathogenic activity of HR-HPV, which is an objective biomarker for clarification of ASCUS-categorized Pap smears in gynecological cytopathology. Furthermore, through comparative analysis, directly visualized p16 immunostaining on smears appears to be a more effective method than HR-HPV viral load for the detection of reactive changes and LSILs from ASCUS-categorized Pap smears.

KW - Atypical squamous cells of undetermined significance

KW - Immunocytochemical detection

KW - p16

KW - Papanicolaou smear

KW - Viral load, high-risk human papillomavirus

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