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or High-Risk Human Papillomavirus (HPV) Status Determine Management of Atypical Squamous Cells Cannot Exclude High-Grade Squamous Intraepithelial Lesion (ASC-H)?
Abstracts Table 1
S39 Histologic and PT Follow-up for LSIL-H PT n
Demographics
Follow-up Type
Histologic Follow-ups
Pap Test Follow-ups
Table 2 1 2 3 4 5 6 7 8 9 10
Median Age Mean Age SD Days to F/U Median F/U Biopsy +/- PT Pap Test Only None Negative CIN1 CIN2 CIN3 Neg. Bx/PAP+ Misc. HSIL ASCH LSILH LSIL ASCUS
1553 1553 857 546 150 199 294 226 43 76 19 54 27 73 139 84
In %
In %
p
In %
< 30
30 and >
All Data
23 23 3.24 187.64 104 49.69 39.00 11.30 21.31 35.86 28.28 4.71 9.22 0.61 9.40 5.74 13.05 24.54 13.84
40 43 11.36 147.33 73.5 64.62 28.55 6.83 25.75 32.25 23.85 5.42 8.40 4.34 11.04 3.07 14.11 27.61 19.02
26 30 12.00 173.35 94 55.18 35.16 9.66 23.22 34.31 26.37 5.02 8.87 2.22 9.89 4.95 13.37 25.46 15.38
.0000 .0000 .0029 .1981 .3616 .4534 .3564 .8844 .8652 .4681 .7907 .6428 .8625 .6167 .4080
55.18 44.82
p < 0.05
34.31 31.39
p 0.295
HPV+ @ LSIL-H Diagnosis Age
F/U Time (days)
F/U Type
F/U Result
33 41 26 34 53 30 46 59 54 34
57 69 123 231 15 46 93 119 259 446
Biopsy Biopsy PT Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy
Negative Negative LSIL CIN1 / NILM CIN1 / LSIL CIN1 CIN1 / ASCUS e HPV+ CIN2-3 / ASCUS e QNS CIN2 / LSILH CIN2 / HSIL
/ PT / PT / / / /
PT PT PT PT
Conclusions: The findings show that a majority of patients who have LSILH by PT do have CIN1 or above on biopsy compared to a negative biopsy (65% vs. 32%, p<0.05); however, we did not find a statistically significant difference between those with CIN2 or above and CIN1 (31.4% vs. 34.3%, pZ0.295). We also found that a majority of patients did receive a biopsy as follow-up compared to either a repeat PT or no follow-up (55% vs. 45%, p<0.05). It also appeared that patients age 30 and over had shorter followup times compared to those under 30. We believe that this is likely due to a higher number of pregnant patients in the cohort under 30 who did not seek follow-up until after their pregnancies. All ten of the cases that had HPV testing done concurrent with the LSIL-H PT were positive. Three of the nine cases with biopsy follow-up showed CIN2 or above. While we still use LSIL-H as a diagnostic category, our data at this time does not demonstrate a statistically significant chance that patients with LSIL-H on PT will have CIN2 or greater lesions found by histologic follow-up for this diagnosis. HPV testing does not appear to be a useful predictor for finding CIN2 or above either and therefore should not be done in cases of LSIL-H. 55 Long Term Cytologic and Histologic Follow-up Result of Adenocarcinoma-In-Situ of Uterine Cervix: Results from a Large Academic Women’s Hospital Zaibo Li, Chengquan Zhao. Pathology, University of Pittsburgh Medical Center, Magee-Women’s Hospital, Pittsburgh, Pennsylvania Introduction: In order to evaluate the occurrence of residual or recurrent disease after conservative conization for adenocarcinoma in situ (AIS) of the uterine cervix, the long term cytologic and histologic follow-up results from patients with cervical AIS were analyzed. Materials and Methods: Pathology records of 136 patients with a biopsy diagnosis of cervical AIS between 2000 and 2010 treated by conization and with cytologic/histologic follow-up were reviewed retrospectively. Results: 100 patients (73.5%) had negative and 36 (26.5%) had positive resection margins of the conization specimen Of the 100 patients with negative margins, 36 underwent subsequent hysterectomy and no residual AIS/invasive carcinoma was identified. 36 patients with positive margins received subsequent hysterectomy and 17 patients (47.2%) had residual AIS. Then these 136 patients were stratified by conization only (64 patients) and hysterectomy (72 patients) to analyze the histologic and cytologic follow up results.
64 patients with conization only, had an average age of 30 years (range: 18-75), the period between diagnosis and conization of 2 months (range: 0.5-8), and total follow-up time of 43 (range: 0.5-117) months after conization. 72 patients with conization followed by hysterectomy had an average age of 39 years (range: 26-63), the period between diagnosis and hysterectomy of 4.3 months (range: 0.5-7), and total follow-up time of 46 months after hysterectomy (range: 0.5-129). Among 64 patients with conization only, 47 had histologic follow-up showing 38 with negative findings and 9 with CIN1.17 patients had cytologic follow up only, showing 9 with negative findings, 6 with ASCUS, and 2 with LSIL. 29 of 64 patients with conization only, had HPV testing results during the follow-up period. HPV positive rate was 10.3% (3/29), No cervical AIS or invasive carcinoma or HSIL were identified during the follow-up period. Among the 72 patients with conization and hysterectomy, 11 had histologic follow-up showing 8 with negative findings and 3 with VAIN1. 61 patients had cytologic follow up only showing 48 with negative findings, 11 with ASCUS, and 2 with LSIL. 27 patients with hysterectomy had HPV testing results. HPV positive rate was 7.4% (2/27). Conclusions: Patients with positive resection margins after conization for AIS of the uterine cervix are significantly more likely to have residual disease. However, negative resection margin carries a very lower risk for residual AIS; therefore conservative management with careful surveillance seems to be feasible in younger women who wish to preserve their fertility. Among 136 women with AIS and with either cervical conization or hysterectomy, no patient showed cervical high grade squamous or glandular dysplasia within the follow-up period. Table 1 Follow-up
Histology Cytology Total Cases
Cytologic and Histologic Follow-up Results of AIS after Treatment Cone only
Hysterectomy
Negative
ASCUS (cytology)
CIN1/LSIL
Total
Negative
ASCUS (cytology)
VAIN1/LSIL
Total
38 9 47
N/A 6 6
9 2 11
47 17 64
8 48 56
N/A 11 11
3 2 5
11 61 72
56 Should Age and/or High-Risk Human Papillomavirus (HPV) Status Determine Management of Atypical Squamous Cells Cannot Exclude High-Grade Squamous Intraepithelial Lesion (ASC-H)? Mohiedean Ghofrani, MD, MBA. Department of Pathology and Cytopathology, PeaceHealth Laboratories, Vancouver, Washington Introduction: According to the 2006 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests, women with a cytology diagnosis of ASC-H should be referred to colposcopy regardless of other clinico-pathologic factors such as age or HPV status. However, given the prevalence of benign postmenopausal atrophy in women above age 50 (which may be diagnosed as ASC-H) and the lower prevalence of HPV in older women, in this study the age and HPV status of women with ASC-H was correlated with subsequent biopsy findings to determine whether one or both of these factors may predict the chance of identifying cervical intraepithelial neoplasia 2 or higher (CIN 2+) on histologic follow-up. Materials and Methods: All cases of ASC-H processed and reported at Peace Health Laboratories in Vancouver, Washington, from July 2008 through the end of April 2012 were tabulated and the following three additional data elements were recorded: patient age at time of diagnosis, results of HPV testing by Hybrid Capture 2 (if performed on the same specimen or an immediately subsequent stand-alone specimen), and whether or not CIN 2+ was detected on an immediately subsequent incisional or excisional biopsy. Results: During the study period, 506 cases of ASC-H were reported, 182 (36.0%) of which had subsequent histologic follow-up. Among the cases with histologic follow-up, 76 cases (41.8%) were subsequently found to have CIN 2+, in line with the reported literature. When subcategorized by age, this proportion was slightly higher (43.5%) in the 147 women age 50 and younger and lower (34.3%) in the 35 women above age 50. However,
S40 this difference was not statistically significant and the risk of detecting CIN 2+ after a diagnosis of ASC-H in women older than 50 was sufficiently high to clinically warrant referral to colposcopy. HPV testing was performed at the request of the clinician in 127 (25.1%) of all ASC-H cases, with 83 cases (65.4%) testing positive for HPV. When subcategorized by age, 70.4% of 98 women age 50 and younger were HPV-positive, while this proportion in the 29 women above 50 years of age was 48.3%. Although this percentage was significantly lower as confirmed by chi-square testing (p<0.05), the prevalence of HPV in women over 50 was not negligible. Finally, there were only 38 patients for whom both HPV testing results and histologic follow-up were available. Of these, 24 were HPV-positive and 14 were HPV-negative. In the HPV-positive group, approximately half (54.2%) were found to have CIN 2+ on subsequent biopsy, and this proportion was roughly maintained when subcategorized by age. However, in the HPV-negative group, only one 35-year-old woman had CIN 2 on histologic follow-up, and none of the 7 women above age 50 were found to have CIN 2+. Conclusions: This study reaffirms previous reports that both prevalence of HPV and risk of CIN 2+ decrease with age. Furthermore, among patients for whom both HPV results and histologic follow-up were available, none of the women over age 50 who tested negative for HPV had CIN 2+ on biopsy. This finding suggests that by reflex HPV testing in older patients with a cytology diagnosis of ASC-H, colposcopy may be avoided in those who are HPV-negative. Similar studies on a larger scale may support modifying the 2006 Management Guidelines to include reflex HPV testing on all cases of ASC-H and possibly avoiding colposcopy in HPV-negative women. 57 Three-Year Follow-up for Women 30 Years and Older with Negative Pap and Negative Hybrid Capture 2 HPV DNA Testing Results Marilyn Dawlett, CT(ASCP)1, Teresa Kologinczak, CT(IAC)1, Jian-Ping Wang, CT(ASCP)1, Nour Sneige, MD1, Therese Bevers, MD2, Ming Guo, MD1. 1Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas; 2Cancer Prevention Center, The University of Texas MD Anderson Cancer Center, Houston, Texas Introduction: For cervical cancer screening, The American Society for Colposcopy and Cervical Pathology (ASCCP) recommended high-risk human papillomavirus (HPV) DNA testing in conjunction with Pap cytology testing for women 30 years and older at a 3-year screening interval, if both Pap and HPV tests are negative. Recent guidelines (American Cancer Society, American Society for Clinical Pathology, ASCCP) further recommended a 5-year screening interval for women with negative Pap and negative HPV DNA test results. To evaluate the risk of high-grade cervical intraepithelial neoplasm (CIN2/3) in women with negative Pap and negative HPV DNA test results during follow-up, we conducted a 3-year follow-up study of women who visited our center in 2007 and 2008. Materials and Methods: From the institutional database at MD Anderson Cancer Center, we retrieved 10,302 Pap/HPV tests in 8,206 women who visited the Cancer Prevention Center from 2007 to 2011. Among these tests, we identified 2,259 Pap/HPV follow-up tests in 1,787 women who had initially negative Pap and negative Hybrid Capture 2 (HC2) HPV screening results in 2007 and 2008. The follow-up data also included 95 biopsies. We stratified the follow-up data into first-, second-, and third-year intervals after the initial screening with both Pap and HPV negative testing results. The ages of women ranged from 30 to 81 years with a mean of 53 years. Results: Of 1,787 women, 1,317 (73.7%) had 3-year follow-up results. One-year follow-up data for 435 patients and 2-year follow-up data for 308 patients were also reviewed. The distribution of Pap/HPV follow-up results are listed in Table 1. During the follow-up period, 5 women had biopsies of CIN2+ (2 at 2nd year, 2 at 3rd year, and 1 at 4th year from baseline screening). The 5 biopsies were performed because of either abnormal Pap, positive HPV testing results, or both. Of these 5 patients, only one
Abstracts had a remote history of cervical dysplasia. The cumulative risk of CIN2+ during the 3-year follow-up period was 0.28%. Table 1 Distribution of 3-year follow-up results in women with Pap-/HPVscreening results Follow-up Results (Case numbers/%) Pap-/HPV-
Pap-/HPV+ Pap+/HPV- Pap+/HPV+ Pap+
1,714 (76) 55 (2.5)
113 (5)
25 (1)
Pap-
Total
10 (0.5) 342 (15) 2,259 (100)
Pap+: ASC-US and higher
Conclusions: We observed a cumulative risk of CIN2+ (0.28%) with the use of 3-year screening intervals in women who had negative Pap and negative HPV DNA test results. Further study is needed to determine the risk of CIN2+ with 5-year screening intervals in women with negative Pap and negative HPV DNA test results. 58 The Influence of Abnormal Pap Test History Prior to Reflex HPV Test on the Subsequent Risk of CIN2+ Isam Eltoum, MD, MBA, Janie Roberson, SCT(ASCP), Allison Wrenn III, CT(ASCP). Pathology, University of Alabama at Birmingham, Birmingham, Alabama Introduction: The objective of this study is to assess the impact of history of abnormal pap tests on subsequent risks of cervical cancer precursors following a reflex HPV test (R-HPV-T) for ASC cytology. Materials and Methods: This is a retrospective study in which the results of reflex HPV test were correlated to the past cytologic results and subsequent outcomes. All women with a diagnosis of ASC and a reflex HPV test in the period Jan 2000 to Nov 2011 were included in the study. Previous history, cytology, histology and Hybrid Capture 2 (HC2) R-HPV-T results were retrieved from the Cerner System and re-entered into SPSS and XLSTAT for statistical analysis. Cumulative risk for HSIL or CIN2+ was calculated from the time of reflex HPV test. Unsatisfactory HPV results were excluded from analysis. Cumulative risk was stratified by age, HPV result and history of abnormal Pap test at various diagnostic categories. The Cox Regression was used to determine the hazard ratio (HR) of CIN2+ using age, history and HPV test results as covariates. Results were considered significant at p < .05. Results: 103,254 women (age 13-95 yr) were screened with 4775 R-HPVT performed. The mean (SD) numbers of pre- and post- R-HPV-T Pap tests were 2.1 (2.3) and 2.9 (2.0) tests, respectively. The ASC-HPV+ rate was 37% (Confidence Interval (CI) 36-38%), higher in those with (46%, CI 4249%) as compared to those without (27% CI, 25-29%) prior history of ASC+. These rates differed also when stratified by history of LSIL+ or HSIL+. The cumulative risk (CR) (CI) for HSIL+ at 3 and 5 years after a positive R-HPV-T were higher 13.3% (11.4, 15.5), 20.7 (18.0, 23.8), compared to that of a negative R-HPV-T, 4.1% (3.3, 5.1), 8.6 % (7.2, 10.2) respectively (p<.05%). The CR (CI) for CIN2+ at 3 and 5 years after a positive R-HPV-T were higher, 10.6% (8.9, 12.6) and 14.2% (11.7, 17.1), compared to that of a negative R-HPV-T, 1.0% (0.7, 1.6) and 1.6% (1.1, 2.5), respectively. These risks were modified by history of abnormal Pap test: the CR (CI) for HSIL+ at 3 and 5 years after a positive R-HPV-T and positive history of ASC+ test were 18.7% (14.8, 23.6) and 26.2% (21.2, 32.5) compared to 3.5% (2.6, 4.8) and 7.1% (5.5, 9.1) after a negative RHPV-T and no history (p<.05%). The CR (SD) for CIN2+ at 3 and 5 years after a positive R-HPV-T and positive history of ASC+ test were 12.2% (8.6, 17.2) and 16.5% (11.6, 23.6) compared to 0.8% (0.4%, 1.5) and 1.1% (0.6, 2.2) after a negative R-HPV-T and no history of ASC+ (p<.05%). The HR, CI, for HSIL or CIN2 after a positive R-HPV-T were 2.6% (2.0, 3.3) and 8.0% (5.1, 12.2), respectively. After controlling for R-HPV-T results, the HR, CI, for HSIL+ and a history ASC+ was 2.2% (1.7, 2.9) while the HR, CI, for CIN2+ after a history HSIL+ was 3.0 %(1.8, 4.9). A history of ASC+ or LSIL+ significantly modified the HR for CIN2 following negative but not positive HPV test. Conclusions: A history of abnormal Pap tests significantly modifies the HPV result positive rate and subsequent risk of high grade cervical cancer precursors.
S39 Histologic and PT Follow-up for LSIL-H PT n
Demographics
Follow-up Type
Histologic Follow-ups
Pap Test Follow-ups
Table 2 1 2 3 4 5 6 7 8 9 10
Median Age Mean Age SD Days to F/U Median F/U Biopsy +/- PT Pap Test Only None Negative CIN1 CIN2 CIN3 Neg. Bx/PAP+ Misc. HSIL ASCH LSILH LSIL ASCUS
1553 1553 857 546 150 199 294 226 43 76 19 54 27 73 139 84
In %
In %
p
In %
< 30
30 and >
All Data
23 23 3.24 187.64 104 49.69 39.00 11.30 21.31 35.86 28.28 4.71 9.22 0.61 9.40 5.74 13.05 24.54 13.84
40 43 11.36 147.33 73.5 64.62 28.55 6.83 25.75 32.25 23.85 5.42 8.40 4.34 11.04 3.07 14.11 27.61 19.02
26 30 12.00 173.35 94 55.18 35.16 9.66 23.22 34.31 26.37 5.02 8.87 2.22 9.89 4.95 13.37 25.46 15.38
.0000 .0000 .0029 .1981 .3616 .4534 .3564 .8844 .8652 .4681 .7907 .6428 .8625 .6167 .4080
55.18 44.82
p < 0.05
34.31 31.39
p 0.295
HPV+ @ LSIL-H Diagnosis Age
F/U Time (days)
F/U Type
F/U Result
33 41 26 34 53 30 46 59 54 34
57 69 123 231 15 46 93 119 259 446
Biopsy Biopsy PT Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy
Negative Negative LSIL CIN1 / NILM CIN1 / LSIL CIN1 CIN1 / ASCUS e HPV+ CIN2-3 / ASCUS e QNS CIN2 / LSILH CIN2 / HSIL
/ PT / PT / / / /
PT PT PT PT
Conclusions: The findings show that a majority of patients who have LSILH by PT do have CIN1 or above on biopsy compared to a negative biopsy (65% vs. 32%, p<0.05); however, we did not find a statistically significant difference between those with CIN2 or above and CIN1 (31.4% vs. 34.3%, pZ0.295). We also found that a majority of patients did receive a biopsy as follow-up compared to either a repeat PT or no follow-up (55% vs. 45%, p<0.05). It also appeared that patients age 30 and over had shorter followup times compared to those under 30. We believe that this is likely due to a higher number of pregnant patients in the cohort under 30 who did not seek follow-up until after their pregnancies. All ten of the cases that had HPV testing done concurrent with the LSIL-H PT were positive. Three of the nine cases with biopsy follow-up showed CIN2 or above. While we still use LSIL-H as a diagnostic category, our data at this time does not demonstrate a statistically significant chance that patients with LSIL-H on PT will have CIN2 or greater lesions found by histologic follow-up for this diagnosis. HPV testing does not appear to be a useful predictor for finding CIN2 or above either and therefore should not be done in cases of LSIL-H. 55 Long Term Cytologic and Histologic Follow-up Result of Adenocarcinoma-In-Situ of Uterine Cervix: Results from a Large Academic Women’s Hospital Zaibo Li, Chengquan Zhao. Pathology, University of Pittsburgh Medical Center, Magee-Women’s Hospital, Pittsburgh, Pennsylvania Introduction: In order to evaluate the occurrence of residual or recurrent disease after conservative conization for adenocarcinoma in situ (AIS) of the uterine cervix, the long term cytologic and histologic follow-up results from patients with cervical AIS were analyzed. Materials and Methods: Pathology records of 136 patients with a biopsy diagnosis of cervical AIS between 2000 and 2010 treated by conization and with cytologic/histologic follow-up were reviewed retrospectively. Results: 100 patients (73.5%) had negative and 36 (26.5%) had positive resection margins of the conization specimen Of the 100 patients with negative margins, 36 underwent subsequent hysterectomy and no residual AIS/invasive carcinoma was identified. 36 patients with positive margins received subsequent hysterectomy and 17 patients (47.2%) had residual AIS. Then these 136 patients were stratified by conization only (64 patients) and hysterectomy (72 patients) to analyze the histologic and cytologic follow up results.
64 patients with conization only, had an average age of 30 years (range: 18-75), the period between diagnosis and conization of 2 months (range: 0.5-8), and total follow-up time of 43 (range: 0.5-117) months after conization. 72 patients with conization followed by hysterectomy had an average age of 39 years (range: 26-63), the period between diagnosis and hysterectomy of 4.3 months (range: 0.5-7), and total follow-up time of 46 months after hysterectomy (range: 0.5-129). Among 64 patients with conization only, 47 had histologic follow-up showing 38 with negative findings and 9 with CIN1.17 patients had cytologic follow up only, showing 9 with negative findings, 6 with ASCUS, and 2 with LSIL. 29 of 64 patients with conization only, had HPV testing results during the follow-up period. HPV positive rate was 10.3% (3/29), No cervical AIS or invasive carcinoma or HSIL were identified during the follow-up period. Among the 72 patients with conization and hysterectomy, 11 had histologic follow-up showing 8 with negative findings and 3 with VAIN1. 61 patients had cytologic follow up only showing 48 with negative findings, 11 with ASCUS, and 2 with LSIL. 27 patients with hysterectomy had HPV testing results. HPV positive rate was 7.4% (2/27). Conclusions: Patients with positive resection margins after conization for AIS of the uterine cervix are significantly more likely to have residual disease. However, negative resection margin carries a very lower risk for residual AIS; therefore conservative management with careful surveillance seems to be feasible in younger women who wish to preserve their fertility. Among 136 women with AIS and with either cervical conization or hysterectomy, no patient showed cervical high grade squamous or glandular dysplasia within the follow-up period. Table 1 Follow-up
Histology Cytology Total Cases
Cytologic and Histologic Follow-up Results of AIS after Treatment Cone only
Hysterectomy
Negative
ASCUS (cytology)
CIN1/LSIL
Total
Negative
ASCUS (cytology)
VAIN1/LSIL
Total
38 9 47
N/A 6 6
9 2 11
47 17 64
8 48 56
N/A 11 11
3 2 5
11 61 72
56 Should Age and/or High-Risk Human Papillomavirus (HPV) Status Determine Management of Atypical Squamous Cells Cannot Exclude High-Grade Squamous Intraepithelial Lesion (ASC-H)? Mohiedean Ghofrani, MD, MBA. Department of Pathology and Cytopathology, PeaceHealth Laboratories, Vancouver, Washington Introduction: According to the 2006 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests, women with a cytology diagnosis of ASC-H should be referred to colposcopy regardless of other clinico-pathologic factors such as age or HPV status. However, given the prevalence of benign postmenopausal atrophy in women above age 50 (which may be diagnosed as ASC-H) and the lower prevalence of HPV in older women, in this study the age and HPV status of women with ASC-H was correlated with subsequent biopsy findings to determine whether one or both of these factors may predict the chance of identifying cervical intraepithelial neoplasia 2 or higher (CIN 2+) on histologic follow-up. Materials and Methods: All cases of ASC-H processed and reported at Peace Health Laboratories in Vancouver, Washington, from July 2008 through the end of April 2012 were tabulated and the following three additional data elements were recorded: patient age at time of diagnosis, results of HPV testing by Hybrid Capture 2 (if performed on the same specimen or an immediately subsequent stand-alone specimen), and whether or not CIN 2+ was detected on an immediately subsequent incisional or excisional biopsy. Results: During the study period, 506 cases of ASC-H were reported, 182 (36.0%) of which had subsequent histologic follow-up. Among the cases with histologic follow-up, 76 cases (41.8%) were subsequently found to have CIN 2+, in line with the reported literature. When subcategorized by age, this proportion was slightly higher (43.5%) in the 147 women age 50 and younger and lower (34.3%) in the 35 women above age 50. However,
S40 this difference was not statistically significant and the risk of detecting CIN 2+ after a diagnosis of ASC-H in women older than 50 was sufficiently high to clinically warrant referral to colposcopy. HPV testing was performed at the request of the clinician in 127 (25.1%) of all ASC-H cases, with 83 cases (65.4%) testing positive for HPV. When subcategorized by age, 70.4% of 98 women age 50 and younger were HPV-positive, while this proportion in the 29 women above 50 years of age was 48.3%. Although this percentage was significantly lower as confirmed by chi-square testing (p<0.05), the prevalence of HPV in women over 50 was not negligible. Finally, there were only 38 patients for whom both HPV testing results and histologic follow-up were available. Of these, 24 were HPV-positive and 14 were HPV-negative. In the HPV-positive group, approximately half (54.2%) were found to have CIN 2+ on subsequent biopsy, and this proportion was roughly maintained when subcategorized by age. However, in the HPV-negative group, only one 35-year-old woman had CIN 2 on histologic follow-up, and none of the 7 women above age 50 were found to have CIN 2+. Conclusions: This study reaffirms previous reports that both prevalence of HPV and risk of CIN 2+ decrease with age. Furthermore, among patients for whom both HPV results and histologic follow-up were available, none of the women over age 50 who tested negative for HPV had CIN 2+ on biopsy. This finding suggests that by reflex HPV testing in older patients with a cytology diagnosis of ASC-H, colposcopy may be avoided in those who are HPV-negative. Similar studies on a larger scale may support modifying the 2006 Management Guidelines to include reflex HPV testing on all cases of ASC-H and possibly avoiding colposcopy in HPV-negative women. 57 Three-Year Follow-up for Women 30 Years and Older with Negative Pap and Negative Hybrid Capture 2 HPV DNA Testing Results Marilyn Dawlett, CT(ASCP)1, Teresa Kologinczak, CT(IAC)1, Jian-Ping Wang, CT(ASCP)1, Nour Sneige, MD1, Therese Bevers, MD2, Ming Guo, MD1. 1Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas; 2Cancer Prevention Center, The University of Texas MD Anderson Cancer Center, Houston, Texas Introduction: For cervical cancer screening, The American Society for Colposcopy and Cervical Pathology (ASCCP) recommended high-risk human papillomavirus (HPV) DNA testing in conjunction with Pap cytology testing for women 30 years and older at a 3-year screening interval, if both Pap and HPV tests are negative. Recent guidelines (American Cancer Society, American Society for Clinical Pathology, ASCCP) further recommended a 5-year screening interval for women with negative Pap and negative HPV DNA test results. To evaluate the risk of high-grade cervical intraepithelial neoplasm (CIN2/3) in women with negative Pap and negative HPV DNA test results during follow-up, we conducted a 3-year follow-up study of women who visited our center in 2007 and 2008. Materials and Methods: From the institutional database at MD Anderson Cancer Center, we retrieved 10,302 Pap/HPV tests in 8,206 women who visited the Cancer Prevention Center from 2007 to 2011. Among these tests, we identified 2,259 Pap/HPV follow-up tests in 1,787 women who had initially negative Pap and negative Hybrid Capture 2 (HC2) HPV screening results in 2007 and 2008. The follow-up data also included 95 biopsies. We stratified the follow-up data into first-, second-, and third-year intervals after the initial screening with both Pap and HPV negative testing results. The ages of women ranged from 30 to 81 years with a mean of 53 years. Results: Of 1,787 women, 1,317 (73.7%) had 3-year follow-up results. One-year follow-up data for 435 patients and 2-year follow-up data for 308 patients were also reviewed. The distribution of Pap/HPV follow-up results are listed in Table 1. During the follow-up period, 5 women had biopsies of CIN2+ (2 at 2nd year, 2 at 3rd year, and 1 at 4th year from baseline screening). The 5 biopsies were performed because of either abnormal Pap, positive HPV testing results, or both. Of these 5 patients, only one
Abstracts had a remote history of cervical dysplasia. The cumulative risk of CIN2+ during the 3-year follow-up period was 0.28%. Table 1 Distribution of 3-year follow-up results in women with Pap-/HPVscreening results Follow-up Results (Case numbers/%) Pap-/HPV-
Pap-/HPV+ Pap+/HPV- Pap+/HPV+ Pap+
1,714 (76) 55 (2.5)
113 (5)
25 (1)
Pap-
Total
10 (0.5) 342 (15) 2,259 (100)
Pap+: ASC-US and higher
Conclusions: We observed a cumulative risk of CIN2+ (0.28%) with the use of 3-year screening intervals in women who had negative Pap and negative HPV DNA test results. Further study is needed to determine the risk of CIN2+ with 5-year screening intervals in women with negative Pap and negative HPV DNA test results. 58 The Influence of Abnormal Pap Test History Prior to Reflex HPV Test on the Subsequent Risk of CIN2+ Isam Eltoum, MD, MBA, Janie Roberson, SCT(ASCP), Allison Wrenn III, CT(ASCP). Pathology, University of Alabama at Birmingham, Birmingham, Alabama Introduction: The objective of this study is to assess the impact of history of abnormal pap tests on subsequent risks of cervical cancer precursors following a reflex HPV test (R-HPV-T) for ASC cytology. Materials and Methods: This is a retrospective study in which the results of reflex HPV test were correlated to the past cytologic results and subsequent outcomes. All women with a diagnosis of ASC and a reflex HPV test in the period Jan 2000 to Nov 2011 were included in the study. Previous history, cytology, histology and Hybrid Capture 2 (HC2) R-HPV-T results were retrieved from the Cerner System and re-entered into SPSS and XLSTAT for statistical analysis. Cumulative risk for HSIL or CIN2+ was calculated from the time of reflex HPV test. Unsatisfactory HPV results were excluded from analysis. Cumulative risk was stratified by age, HPV result and history of abnormal Pap test at various diagnostic categories. The Cox Regression was used to determine the hazard ratio (HR) of CIN2+ using age, history and HPV test results as covariates. Results were considered significant at p < .05. Results: 103,254 women (age 13-95 yr) were screened with 4775 R-HPVT performed. The mean (SD) numbers of pre- and post- R-HPV-T Pap tests were 2.1 (2.3) and 2.9 (2.0) tests, respectively. The ASC-HPV+ rate was 37% (Confidence Interval (CI) 36-38%), higher in those with (46%, CI 4249%) as compared to those without (27% CI, 25-29%) prior history of ASC+. These rates differed also when stratified by history of LSIL+ or HSIL+. The cumulative risk (CR) (CI) for HSIL+ at 3 and 5 years after a positive R-HPV-T were higher 13.3% (11.4, 15.5), 20.7 (18.0, 23.8), compared to that of a negative R-HPV-T, 4.1% (3.3, 5.1), 8.6 % (7.2, 10.2) respectively (p<.05%). The CR (CI) for CIN2+ at 3 and 5 years after a positive R-HPV-T were higher, 10.6% (8.9, 12.6) and 14.2% (11.7, 17.1), compared to that of a negative R-HPV-T, 1.0% (0.7, 1.6) and 1.6% (1.1, 2.5), respectively. These risks were modified by history of abnormal Pap test: the CR (CI) for HSIL+ at 3 and 5 years after a positive R-HPV-T and positive history of ASC+ test were 18.7% (14.8, 23.6) and 26.2% (21.2, 32.5) compared to 3.5% (2.6, 4.8) and 7.1% (5.5, 9.1) after a negative RHPV-T and no history (p<.05%). The CR (SD) for CIN2+ at 3 and 5 years after a positive R-HPV-T and positive history of ASC+ test were 12.2% (8.6, 17.2) and 16.5% (11.6, 23.6) compared to 0.8% (0.4%, 1.5) and 1.1% (0.6, 2.2) after a negative R-HPV-T and no history of ASC+ (p<.05%). The HR, CI, for HSIL or CIN2 after a positive R-HPV-T were 2.6% (2.0, 3.3) and 8.0% (5.1, 12.2), respectively. After controlling for R-HPV-T results, the HR, CI, for HSIL+ and a history ASC+ was 2.2% (1.7, 2.9) while the HR, CI, for CIN2+ after a history HSIL+ was 3.0 %(1.8, 4.9). A history of ASC+ or LSIL+ significantly modified the HR for CIN2 following negative but not positive HPV test. Conclusions: A history of abnormal Pap tests significantly modifies the HPV result positive rate and subsequent risk of high grade cervical cancer precursors.