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Is p16(INK4A) 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.
Gynecol Oncol 2005; 97(1):35-40GO

Abstract

OBJECTIVE

To correlate high-risk human papillomavirus (HR-HPV) viral load to p16(INK4A) 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.

Authors+Show Affiliations

Department of Pathology, School of Medicine, National Defense Medical Center and Tri-Service General Hospital, No. 325, Cheng-Kung Road, Sec. 2, Neihu 114, Taipei, Taiwan, Republic of China. niehshin1014@yahoo.com.twNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15790434

Citation

Nieh, Shin, et al. "Is p16(INK4A) 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." Gynecologic Oncology, vol. 97, no. 1, 2005, pp. 35-40.
Nieh S, Chen SF, Chu TY, et al. Is p16(INK4A) 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. Gynecol Oncol. 2005;97(1):35-40.
Nieh, S., Chen, S. F., Chu, T. Y., Lai, H. C., Lin, Y. S., Fu, E., & Gau, C. H. (2005). Is p16(INK4A) 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. Gynecologic Oncology, 97(1), pp. 35-40.
Nieh S, et al. Is p16(INK4A) 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. Gynecol Oncol. 2005;97(1):35-40. PubMed PMID: 15790434.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Is p16(INK4A) 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-Hwa, PY - 2004/08/24/received PY - 2005/3/26/pubmed PY - 2005/6/23/medline PY - 2005/3/26/entrez SP - 35 EP - 40 JF - Gynecologic oncology JO - Gynecol. Oncol. VL - 97 IS - 1 N2 - OBJECTIVE: To correlate high-risk human papillomavirus (HR-HPV) viral load to p16(INK4A) 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. SN - 0090-8258 UR - https://www.unboundmedicine.com/medline/citation/15790434/Is_p16_INK4A__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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0090-8258(04)00968-0 DB - PRIME DP - Unbound Medicine ER -