Cervical Screening for Cervical Glandular Neoplasia
Cervical Screening for Cervical Glandular Neoplasia
A retrospective study was designed and initiated after obtaining approval from the Institutional Review Board at the University of Pittsburgh Medical Center (UPMC). A computer-based search was carried out on our CoPath Laboratory Information System (LIS) (Cerner Corporation, Kansas City, MO) to retrieve cases with histopathologic diagnoses of cervical AIS, invasive cervical AdCa, or invasive cervical AdsqCa rendered over a study period of almost 10 years between January 1, 2000, and September 30, 2009. The results of surgical pathology reports, preceding Pap test reports, and preceding HPV DNA screening test results were also collected. The UPMC is a large, integrated private health system in which Pap tests are collected by a highly diverse group of clinical providers that includes gynecologists, family physicians, internists, nurse practitioners, physician assistants, and house-staff trainees. Other clinical information, including age and clinical history available in the LIS, was also recorded. Clinical findings such as bleeding or observations of visible cervical lesions were recorded as triggers for diagnostic procedures and histopathologic diagnoses of cervical carcinoma when clinical observations were specifically mentioned but no preceding abnormal screening test results were documented.
All cytologic test results in this study were performed in the cytology laboratory at Magee-Womens Hospital (MWH) of the UPMC and reported using current Bethesda System (TBS) 2001 terminology. Since 2000, conventional Pap smears have been progressively replaced in the laboratory by ThinPrep Pap tests (TPPTs) prepared according to the manufacturer's specifications from PreservCyt samples using an automated processor (ThinPrep 3000; Hologic, Marlborough, MA). Staining of slides was performed on a Sakura Tissue-Tek Automated Slide Stainer (Sakura Finteck USA, Torrance, CA). Since December 2004, location-guided computer-assisted screening of TPPT slides has been used with the ThinPrep Imaging System (TIS) (Hologic). The TIS performs analyses on batches of up to 250 TPPT slides with specialized imaging software. The MWH cytopathology laboratory is a large subspecialized academic hospital laboratory that usually reports more than 100,000 Pap tests per year from a large, integrated hospital health system that serves a metropolitan area with a significantly older population profile than the national average. The reporting profile of the laboratory has been documented in numerous recent publications.
hrHPV DNA testing was ordered by clinicians according to several ordering options as follows: reflex testing triggered by atypical squamous cell (ASC) Pap test results, cotesting with Pap tests in women 30 years and older, and cotesting regardless of either age or Pap test results. hrHPV DNA detection in TPPT PreservCyt (Hologic) vial fluid was performed using the US Food and Drug Administration (FDA)–approved Hybrid Capture 2 assay method (Qiagen, Hinden, Germany), which tests for high-risk and intermediate-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. The results of hrHPV DNA testing were either positive or negative. Women who had equivocal results or residual samples with residual vial fluid volume insufficient for hrHPV DNA testing were excluded from this analysis. When hrHPV DNA was detected in patients with negative Pap cotest results, the Pap test slides were routinely manually rescreened by the screening cytotechnologist, referred for further manual rescreening by a second quality assurance cytotechnologist, and finally also reviewed by a pathologist.
All diagnoses of CGN in this study were established by histopathologic examinations, including endocervical curettage, cervical biopsy, and/or diagnostic excisional procedures by loop electrosurgical excision procedures (LEEP) or cold knife cervical conization. The diagnoses were rendered by subspecialized staff pathologists at MWH whose practices are largely limited to examination of gynecologic and breast pathology specimens. At MWH, all new histopathologic diagnoses of cervical intraepithelial neoplasia (CIN) 2/3, AIS, and cervical carcinoma are confirmed by a second reviewing subspecialized pathologist. Immunohistochemical stains for p16 and Ki-67 are used electively and liberally by staff pathologists to increase the reliability of a CIN2/3 diagnosis. In this report, CIN terminology is used to refer solely to histopathologic results, whereas TBS terminology, such as atypical glandular cells (AGCs), high-grade squamous intraepithelial lesion (HSIL), and low-grade squamous intraepithelial lesion (LSIL), is used to refer solely to Pap test results.
Cytology reports prior to the initial histopathologic diagnosis of cervical neoplasia were recorded. Prior negative Pap tests were routinely rescreened after histopathologic diagnoses of CIN2+ and evaluated as part of departmental quality improvement procedures. Prior abnormal Pap tests were also routinely reviewed and correlated with follow-up histopathology. If an abnormal cytology result occurred within 4 months before the surgical procedure leading to the initial histopathologic diagnosis of CGN, the immediately preceding abnormal Pap test result was regarded as the trigger for surgical intervention leading to histopathologic diagnosis of CGN.
The Pearson χ test was used for statistical analysis (Fisher exact test for small sample sizes), conducted on an SAS 9.1 software (SAS Institute, Cary, NC). A P value less than .05 was considered statically significant.
Materials and Methods
Patient Accrual
A retrospective study was designed and initiated after obtaining approval from the Institutional Review Board at the University of Pittsburgh Medical Center (UPMC). A computer-based search was carried out on our CoPath Laboratory Information System (LIS) (Cerner Corporation, Kansas City, MO) to retrieve cases with histopathologic diagnoses of cervical AIS, invasive cervical AdCa, or invasive cervical AdsqCa rendered over a study period of almost 10 years between January 1, 2000, and September 30, 2009. The results of surgical pathology reports, preceding Pap test reports, and preceding HPV DNA screening test results were also collected. The UPMC is a large, integrated private health system in which Pap tests are collected by a highly diverse group of clinical providers that includes gynecologists, family physicians, internists, nurse practitioners, physician assistants, and house-staff trainees. Other clinical information, including age and clinical history available in the LIS, was also recorded. Clinical findings such as bleeding or observations of visible cervical lesions were recorded as triggers for diagnostic procedures and histopathologic diagnoses of cervical carcinoma when clinical observations were specifically mentioned but no preceding abnormal screening test results were documented.
Cytology Screening Testing
All cytologic test results in this study were performed in the cytology laboratory at Magee-Womens Hospital (MWH) of the UPMC and reported using current Bethesda System (TBS) 2001 terminology. Since 2000, conventional Pap smears have been progressively replaced in the laboratory by ThinPrep Pap tests (TPPTs) prepared according to the manufacturer's specifications from PreservCyt samples using an automated processor (ThinPrep 3000; Hologic, Marlborough, MA). Staining of slides was performed on a Sakura Tissue-Tek Automated Slide Stainer (Sakura Finteck USA, Torrance, CA). Since December 2004, location-guided computer-assisted screening of TPPT slides has been used with the ThinPrep Imaging System (TIS) (Hologic). The TIS performs analyses on batches of up to 250 TPPT slides with specialized imaging software. The MWH cytopathology laboratory is a large subspecialized academic hospital laboratory that usually reports more than 100,000 Pap tests per year from a large, integrated hospital health system that serves a metropolitan area with a significantly older population profile than the national average. The reporting profile of the laboratory has been documented in numerous recent publications.
High-risk HPV DNA Screening Testing
hrHPV DNA testing was ordered by clinicians according to several ordering options as follows: reflex testing triggered by atypical squamous cell (ASC) Pap test results, cotesting with Pap tests in women 30 years and older, and cotesting regardless of either age or Pap test results. hrHPV DNA detection in TPPT PreservCyt (Hologic) vial fluid was performed using the US Food and Drug Administration (FDA)–approved Hybrid Capture 2 assay method (Qiagen, Hinden, Germany), which tests for high-risk and intermediate-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. The results of hrHPV DNA testing were either positive or negative. Women who had equivocal results or residual samples with residual vial fluid volume insufficient for hrHPV DNA testing were excluded from this analysis. When hrHPV DNA was detected in patients with negative Pap cotest results, the Pap test slides were routinely manually rescreened by the screening cytotechnologist, referred for further manual rescreening by a second quality assurance cytotechnologist, and finally also reviewed by a pathologist.
Histopathologic Diagnosis
All diagnoses of CGN in this study were established by histopathologic examinations, including endocervical curettage, cervical biopsy, and/or diagnostic excisional procedures by loop electrosurgical excision procedures (LEEP) or cold knife cervical conization. The diagnoses were rendered by subspecialized staff pathologists at MWH whose practices are largely limited to examination of gynecologic and breast pathology specimens. At MWH, all new histopathologic diagnoses of cervical intraepithelial neoplasia (CIN) 2/3, AIS, and cervical carcinoma are confirmed by a second reviewing subspecialized pathologist. Immunohistochemical stains for p16 and Ki-67 are used electively and liberally by staff pathologists to increase the reliability of a CIN2/3 diagnosis. In this report, CIN terminology is used to refer solely to histopathologic results, whereas TBS terminology, such as atypical glandular cells (AGCs), high-grade squamous intraepithelial lesion (HSIL), and low-grade squamous intraepithelial lesion (LSIL), is used to refer solely to Pap test results.
Cytology reports prior to the initial histopathologic diagnosis of cervical neoplasia were recorded. Prior negative Pap tests were routinely rescreened after histopathologic diagnoses of CIN2+ and evaluated as part of departmental quality improvement procedures. Prior abnormal Pap tests were also routinely reviewed and correlated with follow-up histopathology. If an abnormal cytology result occurred within 4 months before the surgical procedure leading to the initial histopathologic diagnosis of CGN, the immediately preceding abnormal Pap test result was regarded as the trigger for surgical intervention leading to histopathologic diagnosis of CGN.
Statistical Analysis
The Pearson χ test was used for statistical analysis (Fisher exact test for small sample sizes), conducted on an SAS 9.1 software (SAS Institute, Cary, NC). A P value less than .05 was considered statically significant.
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