Unsatisfactory ThinPrep Pap Tests: An Educational Approach to Quality.

Citología en medio líquido (Thin Prep Pap Test). Un año de experiencia

A 2016 survey from Deloitte found that half of physicians were unaware of important changes to the Medicare reimbursement policy that were set to begin on January 1, 2017, and thus questioned the readiness of hundreds of thousands of physicians expected to participate and meet certain performance criteria.1 For pathology, the Medicare reforms could have a $2 billion impact on the specialty during the next several years. All physicians will ease into the new requirements. For instance, with quality measures developed by the College of American Pathologists (CAP), pathologists can prevent a 2019 Medicare financial penalty by reporting on 1 quality measure in 2017. In future years, Medicare will require greater reporting and performance activity from all physicians and group practices in order to avoid decreases in reimbursement.With the expansion of health care fringe benefits during World War II, the advent of Medicare in 1965 under Title XVIII of the Social Security Act, and subsequent health care coverage programs under the control of the Centers of Medicare & Medicaid Services (CMS), the United States has seen a steep rise in health care expenditures. Currently, the CMS provides health care coverage for roughly 105 million beneficiaries at a cost of more than $1.1 trillion annually.2,3 In an effort to hold health care providers accountable for a portion of this increased cost, Congress created the Sustainable Growth Rate (SGR) formula in the Balanced Budget Act of 1997.4 Simplistically, the SGR was an adjustment factor applied to physician fee schedule (PFS) payments that was designed to ensure that the yearly expense per Medicare beneficiary did not exceed the growth in the Gross Domestic Product. However, implementation of this SGR-related PFS update was repeatedly delayed by Congress over the years (the "doc fix"), which eventually led to a potential 27.5–percentage point negative adjustment in PFS payment rates if an alternative to the SGR was not identified. These "doc fixes" also were a factor in the creation of quality pay for performance programs, the first being the Physician Quality Reporting System (PQRS). The PQRS, initially known as the Physician Quality Reporting Initiative, was created within the Tax Relief and Health Care Act of 2006 and made permanent within the Medicare Improvements for Patients and Providers Act of 2008.5,6 Subsequently, the Patient Protection and Affordable Care Act of 2010, commonly referred to as "Obamacare," established the Value-Based Payment Modifier (VBPM) program and the concept of Accountable Care Organizations (ACOs) through the Medicare Shared Savings Programs (MSSPs).7All of these programs had the intent of establishing accountability on the part of the health care provider for the quality and cost of care by linking these to payment. However, despite having these payment adjustment programs in place, the constant threat of a large SGR payment cut remained and made financial planning difficult for physician practices. Congress responded to this concern by passing the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA).8 This legislation was game-changing in that it terminated the never functionally implemented SGR formula, establishing a new framework for rewarding health care providers for better care, not merely more care, and made participation mandatory for all CMS-eligible clinicians (ECs) who wanted to avoid a negative adjustment to their Medicare Part B payments. Under MACRA, the last payment adjustment year related to the PQRS, VBPM, and Electronic Health Record Incentive program (Meaningful Use) will be in 2018, based on January 1, 2016, to December 31, 2016, reporting. In essence, this legislation has bundled all of the prior physician quality reporting programs into one, which the CMS has designated as its Quality Payment Program (QPP). More than 600 000 clinicians will now be reimbursed under the QPP. Initial reporting of metrics for this new program began January 1, 2017, and will close December 31, 2017, with payment adjustments related to this performance period starting in 2019.Within the QPP, there are 2 payment pathways—the Merit-Based Incentive Payment System (MIPS) and the Alternative Payment Model (APM). An EC during the first 2 years is defined by law as any physician, physician assistant, nurse practitioner, clinical nurse specialist, certified registered nurse anesthetist, or any group that includes such professionals and bills CMS for those professional services. In future years, CMS has indicated it anticipates expanding this EC definition. Pathologists at independent laboratories are also considered ECs. This latter point is an important change from the previous quality reporting programs from which they had been excluded, because they were considered Medicare suppliers. Here, we will further describe the details of these 2 payment pathways, based on the CMS's final rule (81 FR 77008), and what you and/or your practice need to do to avoid a potential penalty in 2019.9According to CMS calculations, most ECs will fall into the MIPS pathway. The ECs can be excluded from MIPS by participating in a qualified APM, by not exceeding the low-volume threshold of seeing fewer than 100 Medicare patients or billing CMS less than $30 000 in a year in part B payments on the physician fee schedule, or by being a first-time enrollee in CMS. Based on an EC's or a group's performance within 4 categories, an overall composite performance score (CPS) will be calculated. This CPS is what will be used to compare the EC or the group to the rest of those within the MIPS and determine the potential bonus or penalty they will receive. The potential impact on CMS payments in 2019 from MIPS performance in 2017 is ±4%: this increases to ±5% in 2020, ±7% in 2021, and then ±9% in 2022 and beyond. The performance adjustments are budget neutral, such that the total amount of penalties and bonuses will equal zero.The 4 categories within MIPS are—Quality, Clinical Practice Improvement Activities (CPIAs), Advancing Care Information (ACI), and Resource Use. The requirements within each category can change depending on whether or not an EC is considered "patient facing" or "non–patient facing." This distinction is critical because performance requirements can differ between the 2 groups. According to the 2016 final rule, a non–patient facing EC must bill 100 or fewer patient-facing encounters in a calendar year. For those in a group, 75% of the ECs must fall within the above definition in order for the group to be considered non–patient facing. According to CMS, ECs and groups will be notified of their classification at the start of each performance year. A final list of what qualifies as a patient-facing encounter is available at the CMS Web site (Quality Measure Encounter Codes; accessed January 24, 2017), but the ones most likely to affect pathologists include apheresis, bone marrow biopsy procedure, and evaluation and management CPT codes. Based on a preliminary analysis by CMS, most pathologists will be classified as non–patient facing.In order to ease transition into the new program, CMS has made several options available for reporting in 2017. In order to avoid a penalty in 2019, an EC or group simply must report something within one of the performance categories—for example, one quality measure, regardless of the number of cases—or attest to one CPIA, such as providing timely communication of test results. By simply reporting on one measure or activity, the EC and/or group will avoid the 4% downward payment adjustment in 2019. Other potential participation options include a partial year of reporting—meaning at least 90 days' worth of patient data—or a full year of reporting. Those that chose 1 of these 2 latter options would be eligible for a partial or a full bonus, respectively. The CMS has acknowledged that most small practices would be at a disadvantage and would likely have received a penalty in 2019 without these transition year rules.Within the Quality performance category, an EC or group must report on 6 applicable measures, or all that apply to them if they do not qualify for reporting 6 measures. Depending on the reporting mechanism, the reported data must be on at least 50% of their Medicare patients if done via claims reporting, or 50% of all their patients (regardless of payer) if using another reporting mechanism. For 2017, the CMS has maintained all 8 current CAP–developed quality measures (Table 1). There are other measures available that may apply to a limited number of pathologists and are only reported via a registry. If an EC is unsure if he or she qualifies for additional measures, the EC may contact CMS at the Quality Payment Program Service Center at 1-866-288-8292 or use the online measure tool on the CMS Web site (https://qpp.cms.gov/measures/quality; accessed January 4, 2017). Each applicable measure will receive a score ranging from 0 to 10 points depending on the EC's performance compared with others who reported on the same measure. If 6 measures were applicable to the EC, then a total of 60 points would therefore be available in this performance category. The CMS has classified the 2 lung cancer and the melanoma pathology reporting measures as "high-value" and outcome measures. There are potential bonus points available for reporting on the high-value measures.Of all of these performance categories, only the CPIA category represents a new pay-for-performance concept for CMS, where an EC is rewarded for activities such as care coordination, patient engagement, and safety. Within the final rule, there are 6 subcategories with a total of 92 medium- or high-weighted activities that could count toward obtaining the 40 points available in this performance category. As a non–patient facing EC, the EC or his or her group would need to attest to performing 2 medium-weighted or 1 high-weighted CPIA for a minimum of 90 days. In contrast, patient-facing ECs need to report 4 medium-weighted or 2 high-weighted CPIAs for full credit in this category. Some potential activities that pathologists may participate in are listed in Table 2. Reporting will be done via attestation, and future guidance is expected from the CMS regarding this process. Of importance is that those who report individually via claims will also have to attest individually for CPIA. This is in contrast to those reporting as a group, in which they would attest on 1 to 2 items as a group.The ACI performance category is, in essence, the Electronic Health Record Incentive Program (Meaningful Use). Historically, pathologists have been given an exemption from this program because the interoperability and information exchange measures within the program were not applicable to laboratory information systems (LISs). At least at the start of MIPS, it appears this exemption will continue, because non–patient facing clinicians will not be scored in this category. The CMS will reweight this category to zero for non–patient facing clinicians, and will reallocate the percentage value in this category to the Quality performance category in determining the CPS.Similarly, the Resource Use performance category will not be scored in 2017. Therefore, this category will be reweighted to zero for all ECs, with its percentage of the CPS also being reallocated to the Quality performance category. In the future, this performance category will be similar to the VBPM program but focused solely on claims-based cost calculation. The CMS will base the resource use score on the patients attributed to an EC. At least initially, it is anticipated that pathologists will not be eligible for patient attribution, and therefore would be ineligible for participation in this category.As previously mentioned, an overall CPS will be calculated based on the performance within each evaluable category and will range from 0 to 100. In 2019, those with a CPS higher than 70 will be eligible for a high-performance bonus. The initial proposed weighting of each category will be 60% of the CPS based on the Quality performance score, 15% based on the CPIA score, and 25% based on the ACI performance score. Resource use for the 2017 reporting year will be 0%. However, for non–patient facing ECs, the ACI category will not apply. Therefore, for most pathologists the CPS will be based solely on Quality (85%) and CPIA (15%).As a case example, a non–patient facing EC has 4 quality measures that apply to him or her, equating to 40 possible points within the Quality performance category. The EC reports on the 2 lung measures, the Barrett esophagus measure, and the colorectal cancer measure, and he or she receives a score of 36 out of 40 points. Plus, the EC receives 2 bonus points for the 2 high-value measures, for a final total of 38 out of 40 points. The Quality performance category would then contribute 81 points toward the CPS (38/40 × 85% = 81). Within the CPIA the EC reports on 1 high-weighted CPIA and receives the full 40 points within that performance category. This would lead to an additional 15 points (40/40 × 15%) toward the CPS, and a final CPS of 96 out of 100 points. In addition to likely doing well compared with other ECs, given a final CPS higher than 70, this EC would be eligible for a high-performance bonus as well.For the purpose of MIPS, there are several reporting options, which are the same as what was available for PQRS. These include claims-based, traditional registry, group practice reporting option, Electronic Health Record, measure groups, and the Qualified Clinical Data Registry (QCDR). Historically, pathologists have primarily used claims-based reporting, with a smaller percentage using a traditional registry, a group practice reporting option, or the Electronic Health Record. Measure groups do not apply to pathology, and until recently a QCDR was not available. The group practice reporting option is available to multispecialty group practices and uses a Web interface for transmitting data for prepopulated quality measures.Other new payment pathways within the QPP are designated as APMs. These are advanced APMs and physician-focused payment models (PFPMs). The APMs are systems that are meant to promote accountability for a patient population, improving care coordination and encouraging the delivery of high-quality care in a cost-conscious manner. Currently, there are no pathology-specific advanced APMs or PFPMs; however, several pathology practices, especially those in some academic and large multi-institutional groups, are participating in this pathway through their involvement in a specific type of ACO. A potential advantage of participating through an advanced APM pathway is that you are excluded from MIPS, and from 2019 to 2024 your entity will receive an automatic 5% bonus. Additionally, starting in 2026, the physician fee schedule update will be 0.75%, as opposed to only 0.25% from those ECs in the MIPS pathway.Advanced APM encompasses MSSP tracks 2 and 3, Next Generation ACO model, Oncology Care model, Comprehensive End Stage Renal Disease model, and Comprehensive Primary Care+ in 2017. These models differ from some other traditional ACOs and MSSP track 1 in that there is substantial financial risk to the entity. These entities must report on measures that are comparable to MIPS, use certified Electronic Health Record technology, and carry substantial financial risk (8% or more of total Medicare revenue or 3% or more of expected Medicare expenditures). Additionally, these entities must meet a percent of revenue or patient threshold that increases each year (Table 3) in order to qualify as an advanced APM and therefore be exempt from MIPS. In 2018, the CMS may expand the program to include MSSP track 1+, a new voluntary bundled payment model, and the Comprehensive Care for Joint Replacement Payment model.The concept of PFPM was created within the MACRA legislation to foster the development of additional APMs for providers who might not be able to participate in existing pathways; however, no definition was provided. The CMS final rule first revealed the definition and fulfillment criteria. In a broad sense, a PFPM is an APM that must include Medicare beneficiaries, is anticipated to reduce cost and/or improve patient care, and closes an existing payment policy gap. The CMS did expand the definition to include nonphysician health care providers. Any group or entity may propose a PFPM by submitting a proposal to CMS with a projection of the anticipated size and scope of the PFPM; description of the burden of disease, illness, or disability on the target population; and an assessment of the financial opportunity. These proposals will be reviewed by the PFPM Technical Advisory Committee, which makes a recommendation to the Health and Human Services Secretary. The models accepted by the CMS will then undergo a process similar to that of other APMs, including public announcement, comment period, and request for applications.Additional information regarding the QPP can be found at https://qpp.cms.gov/ (accessed January 14, 2017). The history of such programs suggests that the MIPS requirements within each performance category will become more complex and demanding in future years. The thresholds have intentionally been set low at the start of the program to ease EC transition into the program and to minimize disruption to the delivery of health care. As ECs become more familiar with the program, reporting requirements will likely increase. Another potential threat to pathology is the retirement of our high-performing measures by the CMS. As a whole, pathology has done well within the PQRS program. The quality gaps initially seen at the time of creation of the measure have diminished, and therefore the need for those measures from the perspective of the CMS is less pronounced. However, CAP is striving to maintain these measures because they ensure that the quality of care that best serves Medicare beneficiaries will be promoted within the pathology community. However, additional measures need to be created to facilitate all pathologists' compliance with the MIPS program. The creation of a pathology-specific QCDR with a broader menu of measures is one potential way to help the pathology community succeed within MIPS. The CAP is currently in the process of introducing such a registry to the medical community.Participation in an APM by a large number of pathologists is not likely at this time. Similarly, pathology practice will not readily lend itself to the development of PFPM, given the broad range of services provided and specialties with which we interact. Although pathologists' services influence a large percentage of spending, we do not directly control a large portion of the total cost of care; therefore, the risk may seem too great for pathologists to participate in these models. However, pathologists must continuously reassess how to best position ourselves for the future.In the short term, it is essential for ECs and/or their groups to be aware that by simply reporting anything in 2017 they will avoid a 4% penalty to the PFS in 2019. For the Quality performance category, this can most easily be done via claims-based reporting, traditional registry, or, if the EC is part of a multispecialty group, the group reporting option Web interface. Information about the pathology-specific quality measures can be found on the CAP Web site within the advocacy pages (http://www.cap.org/web/home/involved/advocacy/physician-quality-reporting-system; accessed January 14, 2017), or on the CMS Web site (https://qpp.cms.gov/measures/quality; accessed January 14, 2017). An alternative way to participate in 2017 to avoid the MIPS negative payment adjustment is to attest to performing a CPIA. A full list of improvement activities can be found at https://qpp.cms.gov/measures/ia (accessed January 14, 2017).The authors would like to acknowledge and express our gratitude to Charles Fiegl, BA, for his expert review of the manuscript.

The Thin Prep Pap Test (Cytyc Corp., Boxborough, MA) received approval by the Food and Drug Administration in May 1996 as an alternative to the traditional conventional smear. The present direct-to-vial study assessed the utility of thin-layer technology for cervicovaginal screening in clinical practice. From May 1997-February 1998 (10 mo), 15,006 cervical smears were processed and evaluated; of these, 5,423 (36.1%) were conventional smears (CS) and 9,583 (63.9%) were Thin Prep slides (TP). Both methods were analyzed to compare specimen adequacy and detection rates of cervical lesions. The TP method reduced the "satisfactory but limited by" rate by 97% and the unsatisfactory rate by 63%. For low-grade squamous intraepithelial lesions (LSILs), TP slides yielded 3.6% (348/9,583) as compared to 0.98% (53/5,423) for CS, an increase of 267%. The TP method detected a threefold increase in the number of high-grade squamous intraepithelial lesions (HSILs) of 1.0% (100/9,583), as compared to 0.3% (17/5,425) for the CS group. The atypical squamous cells of undetermined significance/squamous intraepithelial lesion (ASCUS SIL) ratio was reduced by 54% in the TP group. In routine usage in our laboratory, the Thin Prep Pap Test yielded a significant increase in the detection of LSILs and HSILs as compared to conventional smears. Specimen adequacy was significantly improved.

The ThinPrep Pap Test (Cytyc Corp., Boxborough, MA) was introduced in the Loyola University Medical Center (LUMC) Cytopathology Laboratory in March 1997. This study presents a 26-month retrospective review of the cervicovaginal specimens on all patients who had a cytologic diagnosis of adenocarcinoma either by conventional (CS) or ThinPrep (TP) methods. From March 1997 through May 1999, 16,139 conventional smears and 29,589 TP Pap tests were sent to the LUMC cytopathology laboratory. The three diagnostic glandular categories included: atypical glandular cells of undetermined significance (AGUS); suspicious for adenocarcinoma, endometrial adenocarcinoma, and adenocarcinoma; not otherwise specified (nos). Cytohistologic correlation was performed on all available cases. Since endometrial adenocarcinoma occurs most frequently in peri- and postmenopausal patients, the percentage of patients over the age of 50 was determined for each method; 4,669 (29%) of the women receiving a CS were age 50 or over and 6,839 (23%) of the women who received the TP Pap test were in this age group. Sixteen endometrial lesions were identified on cytology, one (adenocarcinoma) with the CS method and 15 (six AGUS; suspicious for adenocarcinoma, four endometrial adenocarcinomas, and five adenocarcinomas; nos) with the TP method. The one CS case had biopsy confirmation. Fourteen of the 15 TP cases (93%) were confirmed by biopsy; one (7%) case had no follow-up. The TP Pap test yielded a higher percentage of endometrial adenocarcinomas (0.05%) as compared to CS (0.01%). Traditionally, CS has not been a method for the early detection of endometrial glandular lesions. However, of the patients diagnosed as having an endometrial adenocarcinoma in this study, the TP Pap test contributed to an increase in the detection of these lesions as compared to CS. The age group for the two methods was comparable.

Background Point-of-care testing (POCT) at UW Health University Hospital is accredited by the Joint Commission (TJC) while the main laboratory is accredited by the College of American Pathologists (CAP). Consolidating to a single accrediting agency would eliminate the burden of maintaining two separate accreditation programs, and reduce related expenses. In consideration of consolidation, we compared the accreditation requirements between the two agencies for POCT. Methods CAP standards in the All Common (n = 84), POC (n = 62), and Lab General checklists (n = 98) were evaluated for non-waived testing requirements in accordance to the POC test menu. The POC test menu includes the following non-waived tests: activated clotting time, blood gases, urine specific gravity by refractometry, and Tzanck smear; and provider performed microscopy (PPM): wet mount (skin or hair), wet prep, and fern test. A gap analysis was conducted to distinguish differences between CAP and TJC standards and further investigation was initiated when needed. Results The majority of CAP checklist standards aligned with the current processes under TJC. From the CAP All Common checklist, 5 out of 84 standards flagged as a potential gap. One notable difference was found for CAP COM.04250Comparability of Instruments and Methods—Nonwaived testing where comparison studies are required only for instruments and methods under the same CAP number. In contrast, the TJC requires instrument and method comparisons across the entire organization, regardless of separate CLIA certificates or sites. Shifting POC nonwaived tests to CAP would eliminate the need to perform comparisons across different sites, which in our hands has been labor intensive and of little clinical value. From CAP POC checklist, 10 out of 62 standards flagged as potential gaps. Specifically, CAP POC.03800Problem Resolution where the ability to provide prompt resolution for POC issues for all shifts in which POC testing is performed is demonstrated. From the CAP Lab General checklist, 4 out of 98 standards flagged as a potential gap. Specifically, CAP GEN.40470Specimen Collection Training where additional discussion with nursing education would be needed to assess collection training records. The other key difference was with CAP GEN.23584Interim Self-Inspection where self-inspection is required during the interim year. Conclusion Overall, our assessment is that moving non-waived POC testing to CAP will align the requirements for this set of largely hospital based POC tests, where the considerable effort saved from eliminating organization wide instrument/method comparisons could be more effectively applied to expanding our existing CAP mandated interim self-inspections to include nonwaived POCT. Because the vast majority of the waived testing performed at our organization occurs at ambulatory sites under CMS oversight, leaving waived POC tests under TJC oversight was felt to align better. Overall, the POCT requirements under CAP checklists were similar to TJC with minor, but potentially impactful, differences. In our situation, moving nonwaived POC testing to CAP accreditation and keeping waived POC testing under TJC accreditation provided the best balance between quality/patient safety and regulatory administrative effort.

To confirm the accuracy of the ThinPrep Pap Test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) on the basis of histologic diagnosis by biopsy and the detection of human papillomavirus (HPV) DNA in mass screening. A total of 1,997 women residing in Xiangyuan County, Shanxi Province, P.R.C., an area with a high incidence of cervical carcinoma, were enrolled in this study. We collected exfoliative cervical samples from all subjects into a liquid buffer (Preserv-Cyt [Cytyc]) and utilized for both cytologic screening using the ThinPrep Pap Test and HPV DNA testing. Subsequent colposcopic biopsies were taken on all subjects. All the tests were performed in an independent and blinded fashion. We compared the ThinPrep Pap test with colposcopic biopsy and HPV test. High grade squamous intraepithelial lesions (HSIL) (CIN 2/3) were identified in 74 (3.7%) of 1,993 women adequately assessed, and there were 12 cases of squamous cell carcinoma (SCC). The false negative rate of ThinPrep cytology was 3.2% for biopsy-confirmed CIN 3 and 9.3% for CIN 2. Twenty-seven (87%) of the 31 women with biopsy-confirmed CIN 3 and 12 (100%) of 12 with biopsy-confirmed SCC had a diagnosis of either HSIL or greater abnormalities on ThinPrep cytology. In addition, the HPV DNA detection rates offered a good correlation between cytology and biopsy. The ThinPrep Pap performed extremely well in this primary screening trial. We found a good correlation between ThinPrep cytology and colposcopic biopsy on detection of HSIL and SCC; cervical specimens collected in ThinPrep liquid buffer serve as a direct test for HPV as well.

Human papillomavirus DNA detection in ThinPrep Pap test vials is independent of cytologic sampling of the transformation zone

The commercial COBAS Amplicor CT/NG test (Roche Diagnostic Systems, Meylan, France) is a sensitive and specific method for detection of Chlamydia trachomatis infections. This test currently consists of using a nucleic acid amplification method to detect C. trachomatis in first-void urine specimens and in endocervical swabs collected in 2-sucrose-phosphate (2SP) transport medium. We conducted a prospective study to determine whether the automated COBAS Amplicor CT/NG test can detect C. trachomatis in cervical specimens collected in PreservCyt transport medium (ThinPrep Pap Test; Cytyc Corporation, Boxborough, Mass.). PreservCyt medium is used to preserve cervical samples before the preparation of ThinPrep slides. We collected 1,000 cervical specimens from young women (age range, 15 to 25 years) during routine Pap smear tests. Only specimens with normal cytology and in which the gynecologist found no clinical evidence of urogenital infections were selected. The samples were stored in PreservCyt transport medium at 15 to 20 degrees C. C. trachomatis was detected in 22 of the 1,000 cervical specimens that had been stored in PreservCyt. To confirm the positive samples, the test was repeated on new endocervical swab specimens collected in 2SP transport medium. Only 9 of the 22 positive patients agreed to undergo this control, but all 9 retested positive. To evaluate the influence of storage conditions on the sensitivity of the C. trachomatis PCR test, all of the positive samples were stored at 15 to 20 degrees C in PreservCyt transport medium and were retested every 2 weeks for 6 weeks. C. trachomatis was successfully amplified from all 22 specimens for the whole 6-week period. The prevalence of C. trachomatis infection was 2.2% in our study population. These results demonstrate that PreservCyt transport medium is a suitable transport medium for detection of C. trachomatis by the COBAS Amplicor CT/NG test. The ThinPrep Pap Test may enable gynecologists to monitor for both cervical lesions and C. trachomatis infections with a single endocervical specimen.

Web-based synoptic reporting for cancer checklists

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Carcinoma of the Endometrium.

To retrospectively study the HPV DNA assay of residual samples from the ThinPrep Pap Test (Cytyc Corporation, Boxborough, Massachusetts, U.S.A.) PreserveCyt (Cytyc) vial as a quality improvement (QI) indicator for management of patients with abnormal cervical cytology. Six hundred eight residual sample vials of liquid-based Pap-Test specimens were selected for the study based on Pap-test results from October 1998 to March 2001. The specimen vials were forwarded to the reference laboratory (American Medical Laboratories, Chantilly, Virginia, U.S.A.) for HPV DNA assay using the Hybrid Capture System method (Digene Corporation, Gaithersburg, Maryland, U.S.A.). At the time of HPV DNA assay, the residual samples were between 8 days to 10 months old, and each vial contained 4 mL. Of the 608 study cases, 76 were WNL, 115 contained BCC, 172 contained ASCUS, 179 were LSIL and 66 were HSIL. In this study, the 191 WNL and BCC cases were designated as the disease-free control group. The HPV DNA typing results were reported as low-risk, high/intermediate-risk or HPV DNA "not detected" HPV types. The HPV DNA testing results were compared to the Pap-Test diagnoses and statistical analysis performed. The following information reflects the percentage of HPV DNA-positive cases based on the Pap-Test diagnoses: 16.2% in WNL and BCC, 51.1% in ASCUS, 94.4% in LSIL and 98.4% in HSIL. Sensitivity (95.5%), specificity (83.7%), false negative value (4.4%), false positive value (16.2%) and predictive value of a positive (88.3%) and negative (93.5%) Pap-Test were calculated on the basis of HPV DNA testing results for 436 cases that were diagnosed as either SIL or negative (WNL and BCC). ASCUS (172) Pap-Test cases were considered borderline--disease positive and excluded from statistical analysis. The HPV DNA assay of residual samples from ThinPrep Pap-Test liquid-based specimens is an objective adjunct to the gynecologic cytology QI protocol and is the gold standard reference test for triaging women with equivocal cytologic diagnoses. The great value of HPV DNA testing is its high sensitivity (95.5%), specificity (83.7%) and negative predictive value (93.5%). HPV DNA testing results can be used as a tool to better determine the need for referrals for colposcopic biopsy, especially for patients with an ASCUS diagnosis. The residual Pap-Test specimens are stable and reproducible for HPV DNA typing. A working flow chart for our gynecologic cytology QI program was produced from the Pap-Test and HPV DNA assay results. This offer presents the added benefit of minimizing the problem of sample variation. The prevalence of HPV infection was 16.2% in this study.

To the Editor.—Alloimmunization from fetomaternal hemorrhage remains an ongoing cause of hemolytic disease of the fetus and newborn.1 Though failure rates of postnatal prophylaxis have decreased to less than 1% to 2%,2 it is critical to minimize laboratory errors when calculating Rh immunoglobulin (RhIg) dose to prevent maternal alloimmunization. Flow cytometry and the Kleihauer-Betke method are 2 means of calculating the necessary RhIg dose, with flow cytometry considered a more precise, but possibly more expensive, method, and not readily available 24 hours a day.Using data collected by the College of American Pathologists (CAP) fetal red blood cells (RBCs) detection surveys from 2014–2019 (24 proficiency testing samples to approximately 50 laboratories using flow cytometry and 1000 laboratories using Kleihauer-Betke) where the recommended RhIg dose was calculated from mean reported values with the CAP RhIg Dose Calculator,3 we compared differences in dose calculation. Paired t tests were used to assess differences in mean reported percentage of fetal RBCs and recommended RhIg dose. Results showed that laboratories using Kleihauer-Betke overestimated the percentage of fetal RBCs on average by 0.221% more (5.292 total percentage points over 24 instances) (95% CI, 0.213%–0.227%), with a standard deviation of 0.190. In 6 of 24 CAP surveys (25%), this average increase in reported fetal RBCs resulted in an increase of RhIg dose by 1 vial. In no instances did the Kleihauer-Betke method lead to a dose recommendation lower than the flow cytometry results.Inherent limitations to using Kleihauer-Betke include lack of standardization, associated labor to perform, and relative imprecision with a coefficient of variation of 30% to 80% as demonstrated in the past 5 years of CAP proficiency testing (2016–2020).4 Advantages include its ease of access, inexpensive cost, and lack of special equipment needed. Although flow cytometry can analyze a larger batch of samples—resulting in greater quantitative accuracy and reproducibility, is more precise with a coefficient of variation less than 20%, and can distinguish between adult F and fetal cells, it is relatively more expensive, time-consuming, and inaccessible.5Ultimately, Kleihauer-Betke is a less precise measure of fetomaternal hemorrhage quantification than flow cytometry; however, on average it will result in a similar to increased recommended dose of RhIg. Given the low incidence of severe adverse reactions to RhIg for antenatal and postnatal prophylaxis, greater RhIg dosing by 1 vial one-fourth of the time is generally safe. The risks of RhIg do not exceed risks associated with any other pooled human product, few incidents of viral transmission have been reported in North America, and RhIg is currently manufactured with viral inactivation products.6 Flow cytometry is currently not feasible for many laboratories owing to the need for special equipment and longer duration of turnaround times, which can impact patient care. Therefore, Kleihauer-Betke remains an adequate method for assessing fetal-maternal hemorrhage and RhIg dose. Standardizing training and methods for using Kleihauer-Betke may improve precision. Regardless of method used to quantify fetomaternal hemorrhage, use of tools including the CAP RhIg Calculator can improve quality of patient care and reduce inadequate dosing.3The authors thank Mary Griffin, MD, for her work in the initial data collection and analysis for this study.

To evaluate the clinical significance of "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" ASC-H by comparing the original cytologic findings with follow-up tissue biopsies, and its association with high-risk HPV. A total of 235,518 ThinPrep Pap tests were performed at our institution from January 2008 through December 2010, but only 727 (0.3%) of these cases were diagnosed as ASC-H. Of the 309 cases diagnosed as ASC-H on cytology for which follow-up histologic material was available, 120 (38.8%) were definitively diagnosed as high-grade dysplasia (CIN 2/3) and 75 (24.2%) showed features of low-grade dysplasia (CIN 1). We observed that the incidence of dysplasia in patients less than 30 years of age was 73.4% (113/154) and 48.3% (14/29) in patients greater than 49 years of age (p = 0.001). There were 71 cases for which high-risk HPV DNA testing was conducted. HPV DNA was found to be positive in 41 of the dysplastic cases (CIN 1 = 18 cases and CIN 2/3 = 23) and negative in six of the dysplastic cases (CIN1 = 2 and CIN2/3 = 4). We conclude that cases diagnosed as ASC-H should be followed-up with caution as they are strongly associated with dysplasia of any grade (63.1%), especially high-grade dysplasia (38.8%). Reflex HPV DNA testing is an important predictor of dysplasia with a positive predictive value of 87.2% in our study.

Roberts, Jennifer M.; Gurley, A. Marian; Thurloe, Julia K.; Bowditch, Ronald; Laverty, Colin R. A. Author Information

ObjectiveCervical cancer ranks as the fourth most prevalent cancer among women globally; it originates in the cervix and has a significant association with human papillomavirus (HPV) infection. The purpose of this study was to investigate the diagnostic utility of cell block (CB) preparations from liquid-based cytology samples in identifying cervical lesions among Turkish patients with HPV. This approach was intended to supplement conventional Pap smear tests and HPV testing.Material and MethodsA retrospective analysis was conducted on 60 HPV-positive cervical smear samples processed through the ThinPrep Pap test. CBs were prepared from liquid-based residues, stained with hematoxylin and eosin, and analyzed. Cytological diagnoses were compared with histopathological findings from colposcopy-guided biopsies. The relationships between the Pap smear, CB, and biopsy results were statistically analyzed.ResultsPap smear cytology identified 1.6%, 16.6%, 43.3%, and 3.3% as high-grade squamous intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells of undetermined significance, and atypical squamous cells - HSIL cannot be excluded + LSIL, respectively. The CB evaluations classified 6.6% of the samples as cervical intraepithelial neoplasia (CIN)1, 1.6% as CIN2, and 1.6% as squamous cell carcinoma (SCC), with 78.3% deemed negative. Histopathological biopsy revealed CIN1 in 11.7%, CIN2 in 1.7%, and CIN3 in 8.3% of the patients. High concordance was observed between the Pap smear and CB diagnoses for negative and low-grade lesions, although discrepancies occurred in higher-grade lesions. HPV testing revealed 65% high-risk positivity, predominantly for HPV16 and HPV18. Significant correlations were found among HPV subtype positivity, CB, and biopsy diagnosis (P < 0.05).ConclusionCB preparations provide enhanced diagnostic accuracy for high-grade lesions and SCC, thus complementing Pap smear cytology and HPV testing. This approach supports their integration into the routine cervical cancer screening protocols in Türkiye. Further global, multicenter studies are recommended to validate these findings.