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Patients with Positive HPV Genotypes 16 and 18 Have Higher Risk to Develop High-grade Squamous Intraepithelial Lesions
S40
Abstracts
Table 1 Cytology/ HPV results
Negative/ Hr HPV+ ASCUS/ HrHPV+ ASCUS/ HrHPVTotal
Histology Results Benign
Low grade (Koilocytosis, CIN1)
High grade (CIN2 and above)
Total
Age <30
Age 30
Age <30
Age 30
Age <30
Age 30
9 (6.0%) 204 (22.74%) 44 (18.18%) 257 (19.95%)
81 (54.36%) 234 (26.08%) 123 (50.83%) 438 (34%)
11 (7.38%) 210 (23.41%) 23 (9.50%) 244 (18.94%)
39 (26.17%) 150 (16.72%) 47 (19.42%) 236 (18.32%)
3 (2.01%) 54 (602%) 2 (0.83%) 59 (4.58%)
6 (4.02%) 45 (5.01%) 3 (1.24%) 54 (4.19%)
149 (100%) 897 (100%) 242 (100%) 1,288 (100%)
71 Cervical Biopsy and Endocervical Currettage Results in Women with Negative Cytology and Positive hrHPV Screen and DNA Genotyping HPV16/18 Marguerite Pinto, MD, Deborah Albert, CT(ASCP), Jean Selleck, CT(ASCP). Bridgeport Hospital, Bridgeport, Connecticut Introduction: The results of the ATHENA trial support the American Society of Colposcopy and Cervical Pathology(ASCCP) guidelines for cotesting women with negative cytology (WNL) for High Risk Human Papilloma Virus (hrHPV) and reflexing to DNA genotyping HPV16/18 if the hrHPV screen is positive. HPV16/18 positive may be referred for immediate colposcopic evaluation as Cervical Intraepithelial Neoplasia (CIN) 2 or higher was detected in 1.2 % of women examined.The overall prevalence rates for hrHPV by cobas was 6.7%, HPV16: 1.0%, HPV18: 0.5%, other hrHPV 5.2%, with HPV16 having the highest absolute risk of CIN2 or CIN3. The aims of this study were 1) to correlate the results of colposcopic directed cervical biopsy (CB) and endocervical currettage (ECC)in WNL with positive HPV16/18 genotyping 2) Re -review WNL in cases of positive HPV16/18 genotyping Materials and Methods: From Dec 2012 to March 2014, 2790 consecutive SurePath (SP) obtained by spatula/cytobrush were examined. WNL 2219 (80%), 1137 of which were sent for hrHPV screen and reflexing to DNA genotyping HPV16/18 (Roche cobas 4800) if positive. The validation for use of SP for HPV screen and genotyping HPV16/18 using Roche cobas 4800 was done by the reference laboratory. 21/26 (80%) with positive HPV16/18 had a colposcopic CB and/or ECC within 4-6 weeks of diagnosis by a gynecologist. All WNL positive HPV16/18 SP were reviewed twice for quality assurance purposes, by the initial sign-out pathologist and retrospectively for the study by the cytopathologist. Results: 82 of 1137 were positive for hrHPV (7.2%), HPV16/18: 26 (2.2%) {HPV16 12/26 (46%), HPV18 13/26(50%) Both 1(3.8%) Other 56(68%)}. All HPV16/18+ SP on review were WNL except for a single ASCUS. CB/ ECC: CIN 2: 2(7.6%) , each HPV 16 or 18; CIN 1: 3(11.5%), 1 HPV16 and 2 HPV18. Conclusions: DNA HPV16/18 genotyping with colposcopic CB/ECC in WNL SP is superior to cytology for the detection of CIN 2. 72 Significance of Cytopathologist Review of Pap Tests Screened as Negative for Intraepithelial Lesion or Malignancy that are HrHPV Positive Vighnesh Walavalkar, MD1, Andrew Fischer, MD2, Christopher L. Owens, MD2. 1University of Massachusetts, Boston, Massachusetts; 2University of Massachusetts Medical School, Boston, Massachusetts Introduction: Cytopathologist review of Pap Tests (PTs) screened by cytotechnologists as negative for intraepithelial lesion or malignancy
(NILM) that are positive for high-risk human papillomavirus (hrHPV+) may be a useful part of a laboratory’s quality control (QC) program. Materials and Methods: During 2012, consecutive PTs interpreted by a cytotechnologist as NILM that were hrHPV+ were referred to a cytopathologist for review before report issuance as part of routine QC. HrHPV status was known at the time of both screening and final review. Results: Cytopathologist review upgraded 250/1282 (19.5%) PTs by one step to atypical squamous cells of undetermined significance and 13 (1%) were upgraded by two steps or more to low-grade squamous intraepithelial lesion or higher (Table 1). During the same period of time, significantly fewer NILM PTs (of unknown hrHPV status) were upgraded by two steps or more as a result of random re-screening by cytotechnologists (0.2%, P Conclusions: Cytopathologist review of PTs screened by cytotechnologists as NILM that are hrHPV+ identified more two-step discrepancies than random re-screening of NILM PTs. Significantly more patients in the upgraded group were found to harbor CIN2+; however this could be related to the higher rate of referral to colposcopy in this group. Table 1
Case Case Case Case Case Case Case Case Case Case Case Case Case
1 2 3 4 5 6 7 8 9 10 11 12 13
Summary of Two-Step Discrepant Cases Final PT diagnosis
Follow-up
ASC-H ASC-H ASC-H ASC-H LSIL LSIL LSIL LSIL LSIL LSIL LSIL LSIL LSIL
CIN2 on immediate biopsy. CIN2 on immediate biopsy, confirmed by LEEP. Follow-up PT ASCUS. Follow-up PT LSIL, subsequent biopsy CIN2. CIN1 on immediate biopsy. Follow-up PT LSIL, subsequent biopsy CIN1. No follow-up. No follow-up. Immediate biopsy negative and follow-up pap NILM. No follow-up. CIN1 on immediate biopsy. CIN1 on immediate biopsy. Follow-up PT NILM.
PT Z Pap Test, ASC-H Z atypical squamous cells-cannot rule out high-grade intraepithelial lesion, LSIL Z low-grade squamous intraepithelial lesion, CIN Z cervical intraepithelial neoplasia, NILM Z Negative for intraepithelial lesion or malignancy
Table 2
Follow-up Data, NZ740
Referral to colposcopy, n(%) CIN2+, n Percentage of total patients with CIN2+ Percentage of biopsied patients with CIN2+
Cases upgraded from NILM (nZ202)
Cases that remained NILM (nZ538)
P Value
138(68.3%)
164(30.5%)
<.001
18 8.9
16 3.0
– <.01
13.1
9.8
.47
NILMZ Negative for intraepithelial lesion or malignancy, CINZ cervical intraepithelial neoplasia
73 Patients with Positive HPV Genotypes 16 and 18 Have Higher Risk to Develop High-grade Squamous Intraepithelial Lesions Joshua Jeanty, MD, David Chhieng, MD, Ozlen Saglam, MD. Yale University, New Haven, Connecticut Introduction: Positive human papillomavirus (HPV) test influences management of patients with an Atypical Squamous Cells of Undetermined Significance (ASCUS) diagnosis. Persistent infection with high-risk HPV genotypes is the cause of squamous intraepithelial lesions that can lead to cervical cancer. The objective is to compare outcomes of high-risk HPV genotypes 16 and 18 versus all other high-risk HPV genotypes tested by the Roche cobas 4800-HPV test system on BD SurePathTM and ThinPrep specimens.
Abstracts
S41
Materials and Methods: From August 2011 to December 2012, 762 patients with ASCUS diagnosis and reflex or co-testing were selected for the study. The high-risk HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 were tested in liquid-based specimens. Follow-up data was obtained from hysterectomy and cone biopsy specimens, loop electrosurgical excision procedures, cervical and vaginal biopsies, endocervical curettings and Pap smears. Final diagnosis was categorized into high-grade, low-grade lesions or negative result. All high-grade lesions were diagnosed by histology within 6 months following cytologic diagnosis. Results: HPV genotypes 16 and 18 were evaluated on 320 specimens with 282 having recorded follow-up surgical diagnosis. High-grade lesions were found in 25% (3/12 cases) of HPV 18 positive, 13% (6/46 cases) in patients with HPV 16 positive, and 4% (10/224 cases) in patients with high-risk HPV genotype that is neither 16 nor 18. Patients with HPV genotypes 16 or 18 positive have a 3.5 fold increased risk of high-grade lesions [OR (95% CI): 3.48 (1.35-8.95)] when compared to other high-risk HPV genotypes. An adenocarcinoma in-situ case was diagnosed in a patient with HPV 18 genotype. Conclusions: Patients with HPV genotypes 16 or 18 have a 3.5 -fold increased risk of developing high-grade lesions when compared to patients with other high-risk HPV genotypes. These genotypes can detect a subgroup of patients who are more likely to develop high-grade lesions. 74 A Five Year Follow Up of Atypical Squamous Cells of Undetermined Significance and ASCUS-H on Sureprep Liquid Based Pap Tests and High Risk Human Papilloma Virus Testing in the Post Partum Patient Diane Kuebler, BS, CT(ASCP), Drucilla Roberts, MD. Massachusetts General Hospital, Boston, Massachusetts Introduction: An ASCUS or ASCUS-H diagnosis in the postpartum patient can lead to additional medical care, expense and present a diagnostic challenge to the cytopathologist due to the presentation of the cellular pattern of a postpartum sample. A review of the Pap tests and HR HPV results and long term follow-up can lead to a more accurate evaluation and clinical presentation of the sample. Materials and Methods: A computerized search of in-house deliveries was performed for 2008. Preliminary analysis of the first two months revealed 569 patients; of these, 520 had a postpartum Pap test. Of these Pap tests, 16 (3.07%) were diagnosed as ASCUS or ASCUS-H. All had HR HPV testing performed. Results: See Table 1 Of these 16 cases, follow-up of one or more years (up until 5) was available on 11 patients. These 11 patients who were diagnosed as ASCUS or ASCUS-H on liquid based pap tests, did not progress to dysplasia. Conclusions: The prevalence of ASCUS or ASCUS-H is low in the postpartum patient Pap test and the clinical follow-up is benign. Table 1 Diagnosis
HR HPV negative
HR HPV positive
ASC ASC-H
6 1
9 0
75 Non 16/18 High-risk HPV Predicts Persistence and Progression of Cervical Lesions in Women with Low Grade Intraepithelial Lesion (LSIL) Yasmin Lyons, DO, Aparna Kamat, MD, Haijun (Steve) Zhou, MD, PhD, Christopher Hobday, MD, Mary Schwartz, MD, Dina Mody, MD, Yimin Ge, MD. Houston Methodist Hospital, Houston, Texas Introduction: Persistent high-risk (HR) HPV infection is essential for the development of cervical dysplasia and cervical cancer. Genotyping for HPV
16 and 18 is increasingly used for risk assessment and management. However, 12 other genotypes of non-16/18 HR-HPV have received little attention. The current study was designed to assess the association of HRHPV genotypes with persistence and progression of cervical lesions after an initial cytologic diagnosis of LSIL. Materials and Methods: A cohort of 167 women with LSIL Pap tests between December 1, 2009 and March 30, 2011 were studied. HPV DNA was extracted from residual SurePath specimens and genotypes were determined by DNA microarray representing 40 HPV genotypes. DNA sequencing was used to confirm the microarray data. Follow-up Pap tests and/or biopsies performed within a period of 20 to 46 months after the initial diagnosis were reviewed. Results: Compared to the group of patients whose cervical lesions regressed, those with persistent or progressed lesions were significantly associated with infections of HR-HPV (p<0.008), non-16/18 HR-HPV (p<0.05), and average number of HR-HPV or non-16/18 HPV genotypes per specimen (p<0.007). However, infection with HPV 16 and/or 18 was not significantly associated with persistence or progression of cervical lesions. Conclusions: The majority of abnormal Pap tests in the United States are comprised of ASCUS and LSIL, which currently consumes significant resources due to the inability to determine the high-risk patients who will progress to high-grade cervical lesions. In this study, we demonstrated that infection with non-16/18 HR-HPV, not 16/18 genotypes, was a strong predictor of persistent cervical disease or progression to HSIL in follow-up. Thus, genotyping solely for HPV 16/18 would miss the majority of patients with LSIL who eventually progress to HSIL. Pooled HR-HPV tests have a better predictive value than HPV 16/18 tests in guiding the management of patients with LSIL. 76 Can High-risk HPV Test Be Used for Primary Cervical Cancer Screening for ASC-H Cases Nail Alouch, MD, Jing Liu, PhD MD. University of Texas Medical School, Houston, Texas Introduction: The current management guideline for ASC-H is to perform colposcopy. Recently, FDA has approved HPV DNA testing for primary cervical cancer screening. Can the HPV test be used for primary cervical cancer screening for ASC-H cases? We have reviewed ASC-H cases in our computer file for a period of 4 years and will present the results here. Methods and Material: We searched our computer file between 2010 and 2014 and found 143 (0.5%) cases with a diagnosis of ASC-H from 28,328 Pap tests. High-risk (HR) HPV testing using FDA-approved Cervista HPVHR System was performed on 137 out of 143 cases. Among the 137 cases, 84 cases had adequate histology follow-up including cervical/vaginal biopsy, endocervical curettage, cervical LEEP, endometrial biopsy and hysterectomy within one year after Pap test. Results: Of 84 ASC-H cases with both HR-HPV test and adequate histology follow-up, 50 (59%) were positive and 34 (41%) were negative for HR-HPV. The histology diagnoses in the HR-HPV positive group are 1 (2%) CIN 3 with microinvasion, 20 (40%) high grade squamous intraepithelial lesion (HSIL: CIN 2 and CIN 3), 18 (36%) low grade squamous intraepithelial lesion (LSIL) and 11 (22%) negative results. The histology diagnoses in the HR-HPV negative group are 2 (5.9%) HSIL (1 CIN2 and 1 CIN 1-2), 11 (32.3%) LSIL, 17 (50%) negative and 4 (11.8%) adenocarcinoma (3 endometrial and 1 endocervcial origin). Conclusions: The results of this study indicate that the HR-HPV test appears to be a reliable tool for screening premalignant squamous lesions (CIN 3) and squamous carcinoma in the ASC-H group while the HR-HPV test, as known, should not be used for screening glandular malignancies especially for those of non-cervical origin. The findings of this limited study suggest that HR-HPV testing can be used for primary cervical cancer screening for ASC-H cases. Large series of studies are warranted.
Abstracts
Table 1 Cytology/ HPV results
Negative/ Hr HPV+ ASCUS/ HrHPV+ ASCUS/ HrHPVTotal
Histology Results Benign
Low grade (Koilocytosis, CIN1)
High grade (CIN2 and above)
Total
Age <30
Age 30
Age <30
Age 30
Age <30
Age 30
9 (6.0%) 204 (22.74%) 44 (18.18%) 257 (19.95%)
81 (54.36%) 234 (26.08%) 123 (50.83%) 438 (34%)
11 (7.38%) 210 (23.41%) 23 (9.50%) 244 (18.94%)
39 (26.17%) 150 (16.72%) 47 (19.42%) 236 (18.32%)
3 (2.01%) 54 (602%) 2 (0.83%) 59 (4.58%)
6 (4.02%) 45 (5.01%) 3 (1.24%) 54 (4.19%)
149 (100%) 897 (100%) 242 (100%) 1,288 (100%)
71 Cervical Biopsy and Endocervical Currettage Results in Women with Negative Cytology and Positive hrHPV Screen and DNA Genotyping HPV16/18 Marguerite Pinto, MD, Deborah Albert, CT(ASCP), Jean Selleck, CT(ASCP). Bridgeport Hospital, Bridgeport, Connecticut Introduction: The results of the ATHENA trial support the American Society of Colposcopy and Cervical Pathology(ASCCP) guidelines for cotesting women with negative cytology (WNL) for High Risk Human Papilloma Virus (hrHPV) and reflexing to DNA genotyping HPV16/18 if the hrHPV screen is positive. HPV16/18 positive may be referred for immediate colposcopic evaluation as Cervical Intraepithelial Neoplasia (CIN) 2 or higher was detected in 1.2 % of women examined.The overall prevalence rates for hrHPV by cobas was 6.7%, HPV16: 1.0%, HPV18: 0.5%, other hrHPV 5.2%, with HPV16 having the highest absolute risk of CIN2 or CIN3. The aims of this study were 1) to correlate the results of colposcopic directed cervical biopsy (CB) and endocervical currettage (ECC)in WNL with positive HPV16/18 genotyping 2) Re -review WNL in cases of positive HPV16/18 genotyping Materials and Methods: From Dec 2012 to March 2014, 2790 consecutive SurePath (SP) obtained by spatula/cytobrush were examined. WNL 2219 (80%), 1137 of which were sent for hrHPV screen and reflexing to DNA genotyping HPV16/18 (Roche cobas 4800) if positive. The validation for use of SP for HPV screen and genotyping HPV16/18 using Roche cobas 4800 was done by the reference laboratory. 21/26 (80%) with positive HPV16/18 had a colposcopic CB and/or ECC within 4-6 weeks of diagnosis by a gynecologist. All WNL positive HPV16/18 SP were reviewed twice for quality assurance purposes, by the initial sign-out pathologist and retrospectively for the study by the cytopathologist. Results: 82 of 1137 were positive for hrHPV (7.2%), HPV16/18: 26 (2.2%) {HPV16 12/26 (46%), HPV18 13/26(50%) Both 1(3.8%) Other 56(68%)}. All HPV16/18+ SP on review were WNL except for a single ASCUS. CB/ ECC: CIN 2: 2(7.6%) , each HPV 16 or 18; CIN 1: 3(11.5%), 1 HPV16 and 2 HPV18. Conclusions: DNA HPV16/18 genotyping with colposcopic CB/ECC in WNL SP is superior to cytology for the detection of CIN 2. 72 Significance of Cytopathologist Review of Pap Tests Screened as Negative for Intraepithelial Lesion or Malignancy that are HrHPV Positive Vighnesh Walavalkar, MD1, Andrew Fischer, MD2, Christopher L. Owens, MD2. 1University of Massachusetts, Boston, Massachusetts; 2University of Massachusetts Medical School, Boston, Massachusetts Introduction: Cytopathologist review of Pap Tests (PTs) screened by cytotechnologists as negative for intraepithelial lesion or malignancy
(NILM) that are positive for high-risk human papillomavirus (hrHPV+) may be a useful part of a laboratory’s quality control (QC) program. Materials and Methods: During 2012, consecutive PTs interpreted by a cytotechnologist as NILM that were hrHPV+ were referred to a cytopathologist for review before report issuance as part of routine QC. HrHPV status was known at the time of both screening and final review. Results: Cytopathologist review upgraded 250/1282 (19.5%) PTs by one step to atypical squamous cells of undetermined significance and 13 (1%) were upgraded by two steps or more to low-grade squamous intraepithelial lesion or higher (Table 1). During the same period of time, significantly fewer NILM PTs (of unknown hrHPV status) were upgraded by two steps or more as a result of random re-screening by cytotechnologists (0.2%, P Conclusions: Cytopathologist review of PTs screened by cytotechnologists as NILM that are hrHPV+ identified more two-step discrepancies than random re-screening of NILM PTs. Significantly more patients in the upgraded group were found to harbor CIN2+; however this could be related to the higher rate of referral to colposcopy in this group. Table 1
Case Case Case Case Case Case Case Case Case Case Case Case Case
1 2 3 4 5 6 7 8 9 10 11 12 13
Summary of Two-Step Discrepant Cases Final PT diagnosis
Follow-up
ASC-H ASC-H ASC-H ASC-H LSIL LSIL LSIL LSIL LSIL LSIL LSIL LSIL LSIL
CIN2 on immediate biopsy. CIN2 on immediate biopsy, confirmed by LEEP. Follow-up PT ASCUS. Follow-up PT LSIL, subsequent biopsy CIN2. CIN1 on immediate biopsy. Follow-up PT LSIL, subsequent biopsy CIN1. No follow-up. No follow-up. Immediate biopsy negative and follow-up pap NILM. No follow-up. CIN1 on immediate biopsy. CIN1 on immediate biopsy. Follow-up PT NILM.
PT Z Pap Test, ASC-H Z atypical squamous cells-cannot rule out high-grade intraepithelial lesion, LSIL Z low-grade squamous intraepithelial lesion, CIN Z cervical intraepithelial neoplasia, NILM Z Negative for intraepithelial lesion or malignancy
Table 2
Follow-up Data, NZ740
Referral to colposcopy, n(%) CIN2+, n Percentage of total patients with CIN2+ Percentage of biopsied patients with CIN2+
Cases upgraded from NILM (nZ202)
Cases that remained NILM (nZ538)
P Value
138(68.3%)
164(30.5%)
<.001
18 8.9
16 3.0
– <.01
13.1
9.8
.47
NILMZ Negative for intraepithelial lesion or malignancy, CINZ cervical intraepithelial neoplasia
73 Patients with Positive HPV Genotypes 16 and 18 Have Higher Risk to Develop High-grade Squamous Intraepithelial Lesions Joshua Jeanty, MD, David Chhieng, MD, Ozlen Saglam, MD. Yale University, New Haven, Connecticut Introduction: Positive human papillomavirus (HPV) test influences management of patients with an Atypical Squamous Cells of Undetermined Significance (ASCUS) diagnosis. Persistent infection with high-risk HPV genotypes is the cause of squamous intraepithelial lesions that can lead to cervical cancer. The objective is to compare outcomes of high-risk HPV genotypes 16 and 18 versus all other high-risk HPV genotypes tested by the Roche cobas 4800-HPV test system on BD SurePathTM and ThinPrep specimens.
Abstracts
S41
Materials and Methods: From August 2011 to December 2012, 762 patients with ASCUS diagnosis and reflex or co-testing were selected for the study. The high-risk HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 were tested in liquid-based specimens. Follow-up data was obtained from hysterectomy and cone biopsy specimens, loop electrosurgical excision procedures, cervical and vaginal biopsies, endocervical curettings and Pap smears. Final diagnosis was categorized into high-grade, low-grade lesions or negative result. All high-grade lesions were diagnosed by histology within 6 months following cytologic diagnosis. Results: HPV genotypes 16 and 18 were evaluated on 320 specimens with 282 having recorded follow-up surgical diagnosis. High-grade lesions were found in 25% (3/12 cases) of HPV 18 positive, 13% (6/46 cases) in patients with HPV 16 positive, and 4% (10/224 cases) in patients with high-risk HPV genotype that is neither 16 nor 18. Patients with HPV genotypes 16 or 18 positive have a 3.5 fold increased risk of high-grade lesions [OR (95% CI): 3.48 (1.35-8.95)] when compared to other high-risk HPV genotypes. An adenocarcinoma in-situ case was diagnosed in a patient with HPV 18 genotype. Conclusions: Patients with HPV genotypes 16 or 18 have a 3.5 -fold increased risk of developing high-grade lesions when compared to patients with other high-risk HPV genotypes. These genotypes can detect a subgroup of patients who are more likely to develop high-grade lesions. 74 A Five Year Follow Up of Atypical Squamous Cells of Undetermined Significance and ASCUS-H on Sureprep Liquid Based Pap Tests and High Risk Human Papilloma Virus Testing in the Post Partum Patient Diane Kuebler, BS, CT(ASCP), Drucilla Roberts, MD. Massachusetts General Hospital, Boston, Massachusetts Introduction: An ASCUS or ASCUS-H diagnosis in the postpartum patient can lead to additional medical care, expense and present a diagnostic challenge to the cytopathologist due to the presentation of the cellular pattern of a postpartum sample. A review of the Pap tests and HR HPV results and long term follow-up can lead to a more accurate evaluation and clinical presentation of the sample. Materials and Methods: A computerized search of in-house deliveries was performed for 2008. Preliminary analysis of the first two months revealed 569 patients; of these, 520 had a postpartum Pap test. Of these Pap tests, 16 (3.07%) were diagnosed as ASCUS or ASCUS-H. All had HR HPV testing performed. Results: See Table 1 Of these 16 cases, follow-up of one or more years (up until 5) was available on 11 patients. These 11 patients who were diagnosed as ASCUS or ASCUS-H on liquid based pap tests, did not progress to dysplasia. Conclusions: The prevalence of ASCUS or ASCUS-H is low in the postpartum patient Pap test and the clinical follow-up is benign. Table 1 Diagnosis
HR HPV negative
HR HPV positive
ASC ASC-H
6 1
9 0
75 Non 16/18 High-risk HPV Predicts Persistence and Progression of Cervical Lesions in Women with Low Grade Intraepithelial Lesion (LSIL) Yasmin Lyons, DO, Aparna Kamat, MD, Haijun (Steve) Zhou, MD, PhD, Christopher Hobday, MD, Mary Schwartz, MD, Dina Mody, MD, Yimin Ge, MD. Houston Methodist Hospital, Houston, Texas Introduction: Persistent high-risk (HR) HPV infection is essential for the development of cervical dysplasia and cervical cancer. Genotyping for HPV
16 and 18 is increasingly used for risk assessment and management. However, 12 other genotypes of non-16/18 HR-HPV have received little attention. The current study was designed to assess the association of HRHPV genotypes with persistence and progression of cervical lesions after an initial cytologic diagnosis of LSIL. Materials and Methods: A cohort of 167 women with LSIL Pap tests between December 1, 2009 and March 30, 2011 were studied. HPV DNA was extracted from residual SurePath specimens and genotypes were determined by DNA microarray representing 40 HPV genotypes. DNA sequencing was used to confirm the microarray data. Follow-up Pap tests and/or biopsies performed within a period of 20 to 46 months after the initial diagnosis were reviewed. Results: Compared to the group of patients whose cervical lesions regressed, those with persistent or progressed lesions were significantly associated with infections of HR-HPV (p<0.008), non-16/18 HR-HPV (p<0.05), and average number of HR-HPV or non-16/18 HPV genotypes per specimen (p<0.007). However, infection with HPV 16 and/or 18 was not significantly associated with persistence or progression of cervical lesions. Conclusions: The majority of abnormal Pap tests in the United States are comprised of ASCUS and LSIL, which currently consumes significant resources due to the inability to determine the high-risk patients who will progress to high-grade cervical lesions. In this study, we demonstrated that infection with non-16/18 HR-HPV, not 16/18 genotypes, was a strong predictor of persistent cervical disease or progression to HSIL in follow-up. Thus, genotyping solely for HPV 16/18 would miss the majority of patients with LSIL who eventually progress to HSIL. Pooled HR-HPV tests have a better predictive value than HPV 16/18 tests in guiding the management of patients with LSIL. 76 Can High-risk HPV Test Be Used for Primary Cervical Cancer Screening for ASC-H Cases Nail Alouch, MD, Jing Liu, PhD MD. University of Texas Medical School, Houston, Texas Introduction: The current management guideline for ASC-H is to perform colposcopy. Recently, FDA has approved HPV DNA testing for primary cervical cancer screening. Can the HPV test be used for primary cervical cancer screening for ASC-H cases? We have reviewed ASC-H cases in our computer file for a period of 4 years and will present the results here. Methods and Material: We searched our computer file between 2010 and 2014 and found 143 (0.5%) cases with a diagnosis of ASC-H from 28,328 Pap tests. High-risk (HR) HPV testing using FDA-approved Cervista HPVHR System was performed on 137 out of 143 cases. Among the 137 cases, 84 cases had adequate histology follow-up including cervical/vaginal biopsy, endocervical curettage, cervical LEEP, endometrial biopsy and hysterectomy within one year after Pap test. Results: Of 84 ASC-H cases with both HR-HPV test and adequate histology follow-up, 50 (59%) were positive and 34 (41%) were negative for HR-HPV. The histology diagnoses in the HR-HPV positive group are 1 (2%) CIN 3 with microinvasion, 20 (40%) high grade squamous intraepithelial lesion (HSIL: CIN 2 and CIN 3), 18 (36%) low grade squamous intraepithelial lesion (LSIL) and 11 (22%) negative results. The histology diagnoses in the HR-HPV negative group are 2 (5.9%) HSIL (1 CIN2 and 1 CIN 1-2), 11 (32.3%) LSIL, 17 (50%) negative and 4 (11.8%) adenocarcinoma (3 endometrial and 1 endocervcial origin). Conclusions: The results of this study indicate that the HR-HPV test appears to be a reliable tool for screening premalignant squamous lesions (CIN 3) and squamous carcinoma in the ASC-H group while the HR-HPV test, as known, should not be used for screening glandular malignancies especially for those of non-cervical origin. The findings of this limited study suggest that HR-HPV testing can be used for primary cervical cancer screening for ASC-H cases. Large series of studies are warranted.