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Update on Human Papilloma Virus (HPV)-related Bias on Pap Tests: Follow-up Results
Abstracts
S41 cell of undetermined significance (ASCUS) or higher lesion. Patients’ ages, histopathologic, cytologic, and HPV follow-up results were reviewed. Results: A total of 784 patients were identified. 323 (41.2 %) had at least one follow-up cytology and/or histopathology until 12/31/2015, and no history of squamous intraepithelial lesion (SIL) in the previous 3 years. On follow-up, 2 (0.6%) had biopsy proven cervical adenocarcinoma in situ (AIS), 1 had concurrent high-grade squamous intraepithelial lesion (HSIL); 15 (4.6%) HSIL, 30 (9.3%) LSIL. No invasive cervical carcinoma was documented. Both cases of AIS were associated with HPV16 infection. In the HSIL group, 6 were HPV16+, 2 HPV18+ and 7 with other types of hrHPV infection. In summary, 19.0% (8/42) HPV16+, and 15.4% (2/13) of HPV18+ patients had follow-up HSIL/AIS, while only 2.7% (7/255) of patients with other hrHPV types developed HSIL. Conclusion: These data suggest that the risk for follow-up HSILs (including AIS) in this group is certainly more than minimal, supporting the current recommendations of repeat cotesting after 1 year. Alternatively HPV genotyping might be preferred, given the high rate of HSIL/AIS in HPV16/ 18+ patients.
PST89 Figure 3
HPV Diagnosis Profile: Digene Hybrid Capture 2
Update on Human Papilloma Virus (HPV)-related Bias on Pap Tests: Follow-up Results Erika Doxtader, MD, Dawn Underwood, MS, CT(ASCP), Jennifer Brainard, MD, Deborah Chute, MD. Cleveland Clinic/Cleveland Clinic Foundation, Cleveland, OH
Cytology and HPV co-testing results 2012-2015
PST88 Follow-up Studies of Patients with High Risk Human Papillomavirus (HPV)-Positive, Cytology-Negative Cervical Screening Co-testing Results Yingchun Wang, MD, PhD, Tomi Kuntzman, DO, Christopher Dalton, BS, CT(ASCP), Osama Alassi, MD. Beaumont Health System, Royal Oak, MI Introduction: The 2012 American Society for Colposcopy and Cervical Pathology (ASCCP) Updated Consensus Guidelines recommend that co-testing with high-risk HPV (hrHPV) type assays, and cervical cytology is the preferred screening strategy for women aged 30-64 years. For those women with hrHPV-positive but cytology-negative co-testing, repeat co-testing at 1 year or alternatively HPV genotyping is recommended. However, there is limited follow-up data available on this group of patients from routine US clinical practice settings. Materials and Methods: From 03/12/2014 to12/31/2014, co-testing with Cobas HPV Test (Roche Molecular Systems, Inc.) and Pap cytology with ThinPrep (Hologic, Marlborough, MA) was performed on 11,966 cervical brushing specimens at Beaumont Hospital, Royal Oak, MI. Positive cytology was defined as an interpretation of atypical squamous
Introduction: We have previously shown that knowledge of HPV status influences cytotechnologist (CT) interpretation of Pap tests originally diagnosed as negative for intraepithelial lesion or malignancy (NILM). It remains unclear whether this bias results in increased detection of squamous abnormalities, or is merely over-interpretation of truly negative Pap tests. We now review the follow-up for all patients in the original study. Materials and Methods: Please see our original abstract (JASC 2015: 4(6); S4-S5) for full details. Briefly, 8 cytotechnologists each reviewed 250 Pap test slides twice, only varying knowledge of HPV status. Test cases of NILM Pap tests in the original study were reviewed for follow-up (nZ160), including repeat cytology, biopsies, or HPV testing. The worst pathology was used in the calculation of abnormality rates. Results: Follow-up was available in 64 patients (40%). As expected, more abnormal follow-up was seen in HPV+ patients (see Table 1). In aggregate, CTs were less likely interpret NILM when HPV+ status was known, regardless of follow-up (see Table 2). A detailed review of biopsy proven CIN1+ patients (Table 3) shows similar detection of abnormalities when the HPV status was known and unknown. Conclusion: Although knowledge of HPV+ status significantly biases CTs when evaluating NILM cases, this does not appear to detect cases with abnormalities on follow-up more often than cases with benign follow-up, suggesting that the bias to upgrade known HPV+ cases may lead to increased interventions without significantly improved sensitivity. However, a second review of HPV+ NILM cases at our institution did identify a small number of missed abnormal Pap tests, occurring as often when the HPV status was unknown as when known. This supports the idea of using HPV+ status to select NILM cases for quality control to detect rare cases in which significant lesions were missed.
S42
Abstracts of women undergoing colposcopic evaluations and over-treatment. As a result, ASCCP/ACOG guidelines recommend HPV/Pap co-testing in order to achieve the highest levels of sensitivity and specificity in cervical cancer screening. We sought to determine if upfront knowledge of the HPV status prior to final pathology sign-out results in bias in the interpretation of cervical cytology specimens. Materials and Methods: We retrospectively reviewed cervical cytology reports issued at our institution from 1/1/2014 to 12/10/2015, a period encompassing before (1/1/2014-2/28/2015) and after (4/1/2015-12/10/ 2015) the results of HPV testing were available prior to Pap slides being screened. Each individual pathologist’s difference in Bethesda categorization before and after HPV status was known was computed using Fisher’s exact test. Results: Individually, 8 of 9 pathologists had a statistically significant increase in HPV-positive NILM cases, 3 of 9 pathologists had a significant increase in HPV-positive ASCUS cases (p Z 0.024, 0.016 and 0.0034 respectively) and 1 pathologist’s ASC:SIL ratio decreased significantly (p Z 0.005). No individual had a statistically significant difference in LSIL, ASC-H or HSIL categories. All cases combined, there was a significant increase in the number of HPV-positive NILM and ASCUS cases (p<0.001 and p<0.001 respectively), and a slight increase in the HPV-positive LSIL cases (p Z 0.049), but no significant difference in the ASC-H or HSIL categories, or ASC:SIL ratios. Conclusion: Knowledge of HPV status biased individual pathologists towards ASCUS but not other Bethesda categories. The statistically significant increase in the HPV-positive NILM category was a result of an internal quality assurance measure in which HPV-positive NILM cases were subject to re-screening.
Figure 1
Increase in HR-HPV-positive NILM
PST90 Knowledge of High-Risk HPV Status Prior to Final Pathology Sign-out Biases Cervical Cytology Interpretation Omonigho Aisagbonhi, MD, PhD, Ivan Chebib, MD. Massachusetts General Hospital, Boston, MA Introduction: DNA-based testing for human papillomavirus (HPV) infection is more sensitive than cytology screening by Pap test. However, the prevalence of HPV infection is high and most HPV infections are transient. Therefore, HPV testing alone would likely result in a high number
Figure 2
Increase in HR-HPV-positive ASCUS
S41 cell of undetermined significance (ASCUS) or higher lesion. Patients’ ages, histopathologic, cytologic, and HPV follow-up results were reviewed. Results: A total of 784 patients were identified. 323 (41.2 %) had at least one follow-up cytology and/or histopathology until 12/31/2015, and no history of squamous intraepithelial lesion (SIL) in the previous 3 years. On follow-up, 2 (0.6%) had biopsy proven cervical adenocarcinoma in situ (AIS), 1 had concurrent high-grade squamous intraepithelial lesion (HSIL); 15 (4.6%) HSIL, 30 (9.3%) LSIL. No invasive cervical carcinoma was documented. Both cases of AIS were associated with HPV16 infection. In the HSIL group, 6 were HPV16+, 2 HPV18+ and 7 with other types of hrHPV infection. In summary, 19.0% (8/42) HPV16+, and 15.4% (2/13) of HPV18+ patients had follow-up HSIL/AIS, while only 2.7% (7/255) of patients with other hrHPV types developed HSIL. Conclusion: These data suggest that the risk for follow-up HSILs (including AIS) in this group is certainly more than minimal, supporting the current recommendations of repeat cotesting after 1 year. Alternatively HPV genotyping might be preferred, given the high rate of HSIL/AIS in HPV16/ 18+ patients.
PST89 Figure 3
HPV Diagnosis Profile: Digene Hybrid Capture 2
Update on Human Papilloma Virus (HPV)-related Bias on Pap Tests: Follow-up Results Erika Doxtader, MD, Dawn Underwood, MS, CT(ASCP), Jennifer Brainard, MD, Deborah Chute, MD. Cleveland Clinic/Cleveland Clinic Foundation, Cleveland, OH
Cytology and HPV co-testing results 2012-2015
PST88 Follow-up Studies of Patients with High Risk Human Papillomavirus (HPV)-Positive, Cytology-Negative Cervical Screening Co-testing Results Yingchun Wang, MD, PhD, Tomi Kuntzman, DO, Christopher Dalton, BS, CT(ASCP), Osama Alassi, MD. Beaumont Health System, Royal Oak, MI Introduction: The 2012 American Society for Colposcopy and Cervical Pathology (ASCCP) Updated Consensus Guidelines recommend that co-testing with high-risk HPV (hrHPV) type assays, and cervical cytology is the preferred screening strategy for women aged 30-64 years. For those women with hrHPV-positive but cytology-negative co-testing, repeat co-testing at 1 year or alternatively HPV genotyping is recommended. However, there is limited follow-up data available on this group of patients from routine US clinical practice settings. Materials and Methods: From 03/12/2014 to12/31/2014, co-testing with Cobas HPV Test (Roche Molecular Systems, Inc.) and Pap cytology with ThinPrep (Hologic, Marlborough, MA) was performed on 11,966 cervical brushing specimens at Beaumont Hospital, Royal Oak, MI. Positive cytology was defined as an interpretation of atypical squamous
Introduction: We have previously shown that knowledge of HPV status influences cytotechnologist (CT) interpretation of Pap tests originally diagnosed as negative for intraepithelial lesion or malignancy (NILM). It remains unclear whether this bias results in increased detection of squamous abnormalities, or is merely over-interpretation of truly negative Pap tests. We now review the follow-up for all patients in the original study. Materials and Methods: Please see our original abstract (JASC 2015: 4(6); S4-S5) for full details. Briefly, 8 cytotechnologists each reviewed 250 Pap test slides twice, only varying knowledge of HPV status. Test cases of NILM Pap tests in the original study were reviewed for follow-up (nZ160), including repeat cytology, biopsies, or HPV testing. The worst pathology was used in the calculation of abnormality rates. Results: Follow-up was available in 64 patients (40%). As expected, more abnormal follow-up was seen in HPV+ patients (see Table 1). In aggregate, CTs were less likely interpret NILM when HPV+ status was known, regardless of follow-up (see Table 2). A detailed review of biopsy proven CIN1+ patients (Table 3) shows similar detection of abnormalities when the HPV status was known and unknown. Conclusion: Although knowledge of HPV+ status significantly biases CTs when evaluating NILM cases, this does not appear to detect cases with abnormalities on follow-up more often than cases with benign follow-up, suggesting that the bias to upgrade known HPV+ cases may lead to increased interventions without significantly improved sensitivity. However, a second review of HPV+ NILM cases at our institution did identify a small number of missed abnormal Pap tests, occurring as often when the HPV status was unknown as when known. This supports the idea of using HPV+ status to select NILM cases for quality control to detect rare cases in which significant lesions were missed.
S42
Abstracts of women undergoing colposcopic evaluations and over-treatment. As a result, ASCCP/ACOG guidelines recommend HPV/Pap co-testing in order to achieve the highest levels of sensitivity and specificity in cervical cancer screening. We sought to determine if upfront knowledge of the HPV status prior to final pathology sign-out results in bias in the interpretation of cervical cytology specimens. Materials and Methods: We retrospectively reviewed cervical cytology reports issued at our institution from 1/1/2014 to 12/10/2015, a period encompassing before (1/1/2014-2/28/2015) and after (4/1/2015-12/10/ 2015) the results of HPV testing were available prior to Pap slides being screened. Each individual pathologist’s difference in Bethesda categorization before and after HPV status was known was computed using Fisher’s exact test. Results: Individually, 8 of 9 pathologists had a statistically significant increase in HPV-positive NILM cases, 3 of 9 pathologists had a significant increase in HPV-positive ASCUS cases (p Z 0.024, 0.016 and 0.0034 respectively) and 1 pathologist’s ASC:SIL ratio decreased significantly (p Z 0.005). No individual had a statistically significant difference in LSIL, ASC-H or HSIL categories. All cases combined, there was a significant increase in the number of HPV-positive NILM and ASCUS cases (p<0.001 and p<0.001 respectively), and a slight increase in the HPV-positive LSIL cases (p Z 0.049), but no significant difference in the ASC-H or HSIL categories, or ASC:SIL ratios. Conclusion: Knowledge of HPV status biased individual pathologists towards ASCUS but not other Bethesda categories. The statistically significant increase in the HPV-positive NILM category was a result of an internal quality assurance measure in which HPV-positive NILM cases were subject to re-screening.
Figure 1
Increase in HR-HPV-positive NILM
PST90 Knowledge of High-Risk HPV Status Prior to Final Pathology Sign-out Biases Cervical Cytology Interpretation Omonigho Aisagbonhi, MD, PhD, Ivan Chebib, MD. Massachusetts General Hospital, Boston, MA Introduction: DNA-based testing for human papillomavirus (HPV) infection is more sensitive than cytology screening by Pap test. However, the prevalence of HPV infection is high and most HPV infections are transient. Therefore, HPV testing alone would likely result in a high number
Figure 2
Increase in HR-HPV-positive ASCUS