The Impact of Medicaid Institutions for Mental Disease Exclusion Waivers on the Availability of Substance Abuse Treatment Services and the Varying Effect by Ownership Type.

Policy Points The adoption of Medicaid institutions for mental disease (IMD) exclusion waivers increases the likelihood of substance abuse treatment facilities offering mental health and substance abuse treatment for co-occurring disorders, especially in residential facilities. There are differential responses to IMD waivers based on facility ownership. For-profit substance abuse treatment facilities are responsive to the adoption of IMD substance use disorder waivers, whereas private not-for-profit and public entities are not. The response of for-profit facilities suggests that integration of substance abuse and mental health treatment for individuals in residential facilities may be cost-effective. CONTEXT: Access to integrated care for those with co-occurring mental health (MH) and substance use disorders (SUDs) has been limited because of an exclusion in Medicaid on paying for SUD care for those in institutions for mental disease (IMDs). Starting in 2015, the federal government encouraged states to pursue waivers of this exclusion, and by the end of 2020, 28 states had done so. It is unclear what impact these waivers have had on the availability of care for co-occurring disorders and the characteristics of any facilities that expanded care because of them. METHODS: Using data from the National Survey of Substance Abuse Treatment Services, we estimate a two-stage residual inclusion model including time- and state-fixed effects to examine the effect of state IMD SUD waivers on the percentage of facilities offering co-occurring MH and SUD treatment, overall and for residential facilities specifically. Separate analyses are conducted by facility ownership type. FINDINGS: Results show that the adoption of an IMD SUD waiver is associated with 1.068 greater odds of that state having facilities offering co-occurring MH and substance abuse (SA) treatment a year or more later. The adoption of a waiver increases the odds of a state's residential treatment facility offering co-occurring MH and SA treatment by 1.129 a year or more later. Additionally, the results suggest 1.163 higher odds of offering co-occurring MH/SA treatment in private for-profit SA facilities in states that adopt an IMD SUD waiver while suggesting no significant impact on offered services by private not-for-profit or public facilities. CONCLUSIONS: Our study findings suggest that Medicaid IMD waivers are at least somewhat effective at impacting the population targeted by the policy. Importantly, we find that there are differential responses to these IMD waivers based on facility ownership, providing new evidence for the literature on the role of ownership in the provision of health care.

Role of HPV genotyping in risk assessment among cytology diagnosis categories: analysis of 4562 cases with cytology-HPV cotesting and follow-up biopsies.

OBJECTIVE: Human papilloma virus (HPV) detection and genotyping are increasingly used in clinical risk assessment. We aimed to analyze HPV genotyping performance in risk stratification among cytology diagnosis categories. METHODS: Between January 1, 2015 and December 31, 2016, 4562 cases with cytology-HPV co-testing and biopsy follow-up were identified. HPV tests were performed on Cobas (n=3959) or Aptima (n=603) platforms. Of the biopsies, 669 demonstrated high-grade squamous intraepithelial lesions or worse. RESULTS: Pooled high-risk HPV testing had high overall sensitivity (97%) but low specificity (20%) and positive predictive value (20%) for biopsy-confirmed high-grade squamous intraepithelial lesions or worse. HPV16/18 genotyping had considerably improved specificity (81%) and positive predictve value (35%) in predicting high-grade squamous intraepithelial lesions or worse, especially in atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion categories. Significantly more biopsy-confirmed high-grade squamous intraepithelial lesions or worse were detected by Aptima than Cobas testing, as measured by HPV16/18 (48% vs 33%, p<0.001), non-16/18 high-risk HPV (18% vs 13%, p=0.029), or all high-risk HPV genotypes (27% vs 19%, p<0.001). Aptima genotyping showed a significantly higher positive predictive value than Cobas genotyping for biopsy-confirmed high-grade squamous intraepithelial lesions or worse in the atypical squamous cells of undetermined significance category (47% vs 23%, p<0.05). CONCLUSIONS: HPV genotyping was sensitive for biopsy-confirmed high-grade squamous intraepithelial lesions or worse in all cytologic categories, and is particularly valuable in risk evaluation for women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. The triaging role was greatly diminished in high-risk lesions (atypical glandular cells, atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions) due to low specificity and positive predictive value. Aptima performance in risk management was superior to Cobas, with significantly higher positive predictive value for biopsy-confirmed high-grade squamous intraepithelial lesions or worse. Our results highlight the importance of careful data interpretation from studies using different HPV testing methods and the need to incorporate HPV E6/E7-mRNA testing into management guidelines.

Micropapillary adenocarcinoma of lung: Morphological criteria and diagnostic reproducibility among pulmonary pathologists.

CONTEXT: Invasive micropapillary adenocarcinoma (MPC) is an aggressive variant of lung adenocarcinoma, frequently manifesting with advanced stage lymph node metastasis and decreased survival. OBJECTIVE: Identification of this morphology is important, as it is strongly correlated with poor prognosis regardless of the amount of MPC component. To date, no study has investigated the morphological criteria used to objectively diagnose it. DESIGN: Herein, we selected 30 cases of potential MPC of lung, and distributed 2 digital images per case among 15 pulmonary pathology experts. Reviewers were requested to diagnostically interpret, assign the percentage of MPC component, and record the morphological features they identified. The noted features included: columnar cells, elongated slender cell nests, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial signet ring-like forms, intracytoplasmic vacuolization, multiple nests in the same alveolar space, back-to-back lacunar spaces, epithelial nest anastomosis, marked pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, small/medium/large tumor nest size, fibrovascular cores, and spread through air-spaces (STAS). RESULTS: Cluster analysis revealed three subgroups with the following diagnoses: "MPC", "combined papillary and MPC", and "others". The subgroups correlated with the reported median percentage of MPC. Intracytoplasmic vacuolization, epithelial nest anastomosis/confluence, multiple nests in the same alveolar space, and small/medium tumor nest size were the most common criteria identified in the cases diagnosed as MPC. Peripherally oriented nuclei and epithelial signet ring-like forms were frequently identified in both the "MPC" and "combined papillary and MPC" groups. CONCLUSIONS: Our study provides objective diagnostic criteria to diagnose MPC of lung.

Computational Speedups Using Small Quantum Devices.

Suppose we have a small quantum computer with only M qubits. Can such a device genuinely speed up certain algorithms, even when the problem size is much larger than M? Here we answer this question to the affirmative. We present a hybrid quantum-classical algorithm to solve 3-satisfiability problems involving n≫M variables that significantly speeds up its fully classical counterpart. This question may be relevant in view of the current quest to build small quantum computers.

Aptima Human Papillomavirus E6/E7 mRNA Test Results Strongly Associated With Risk for High-Grade Cervical Lesions in Follow-Up Biopsies.

OBJECTIVE: Human papillomavirus (HPV) tests and genotyping (GT) have been used in clinical risk assessment. The purpose of this study was to analyze the performance of 2 common HPV testing platforms in risk evaluation for high-grade cervical lesions. MATERIALS AND METHODS: Between January 1, 2015, and December 31, 2016, a total of 4,562 Pap tests with follow-up biopsies in our laboratory database were analyzed along with HPV tests performed on Cobas (CHPV, n = 3,959) or Aptima (AHPV, n = 603) platforms. RESULTS: The sensitivity for biopsy-confirmed HSIL or worse lesions was 97% for both CHPV and AHPV (p = .75). AHPV showed significantly lower positive rates than CHPV in benign (56% vs 86%) or LSIL (66% vs 90%) biopsies, resulting in significantly higher specificity for HSIL or worse than CHPV (38% vs 12%, p < .001). AHPV demonstrated significantly higher positive predictive value for HSIL or worse (24% vs 16%, p < .001) and overall accuracy (48% vs 24%, p < .001) than CHPV. AHPV GT also had significantly higher specificity for biopsy-confirmed HSIL or worse than CHPV (88% vs 72%, p < .001) with comparable sensitivity (50% vs 51%, p = .75). Women with HPV 16 on AHPV were significantly more likely to have HSIL or worse on biopsies than those with HPV 16 on CHPV (likelihood ratio = 4.3 vs 2.0, p = .004). CONCLUSIONS: Although both AHPV and CHPV were highly sensitive for biopsy-confirmed HSIL or worse lesions, AHPV and GT demonstrated significantly higher specificity and positive predictive value than CHPV. The difference is probably related to E6/E7 overexpression after viral DNA integration in high-grade lesions. The significantly higher specificity and overall accuracy of AHPV and GT for HSIL or worse lesions may be useful in clinical risk management.

Rapid Adiabatic Preparation of Injective Projected Entangled Pair States and Gibbs States.

We propose a quantum algorithm for many-body state preparation. It is especially suited for injective projected entangled pair states and thermal states of local commuting Hamiltonians on a lattice. We show that for a uniform gap and sufficiently smooth paths, an adiabatic runtime and circuit depth of O(polylogN) can be achieved for O(N) spins. This is an almost exponential improvement over previous bounds. The total number of elementary gates scales as O(NpolylogN). This is also faster than the best known upper bound of O(N^{2}) on the mixing times of Monte Carlo Markov chain algorithms for sampling classical systems in thermal equilibrium.

Exploring the Impact of COVID-19 Restrictions on Nursing Home Residents', Families', and Staff's Perceptions of Bioethical Principles: A Qualitative Study.

In this study, we employed a pre-interview survey and conducted interviews with nursing home staff members and residents/family members to understand their perceptions of whether the COVID-19 restrictions fulfilled obligations to nursing home residents under various principles, including autonomy, beneficence, nonmaleficence, justice, and privacy. We conducted 20 semi-structured interviews with staff members from 14 facilities, and 20 with residents and/or family members from 13 facilities. We used a qualitative descriptive study design and thematic analysis methodology to analyze the interviews. Findings from the pre-interview survey indicated that, compared to nursing home staff, residents and their families perceived lower adherence to bioethics principles during the pandemic. Qualitative analysis themes included specific restrictions, challenges, facility notifications, consequences, communication, and relationships between staff and residents/family members. Our study exposes the struggle to balance infection control with respecting bioethical principles in nursing homes, suggesting avenues for improving processes and policies during public health emergencies.

Atypical glandular cells in Pap tests: cytology-histology correlation and risk assessment with human papillopmavirus (HPV) testing.

INTRODUCTION: Atypical glandular cells (AGC) represent less than 1% of Pap test cases and include a variety of lesions in both the cervix and endometrium. The study aimed to investigate the cytology-histology correlation in AGC patients and to evaluate the clinical utility of hrHPV testing in this diagnostic context. MATERIALS AND METHODS: We identified 491 atypical glandular cells (AGC) cases in our quality analysis (QA) database of 336,064 Pap tests interpreted between March 1, 2013 and July 12, 2016. Of these, 251 cases had follow-up biopsies with hrHPV tests in 148 cases. RESULTS: The most common histologic diagnosis associated with AGC was normal/benign or low-grade lesions, comprising 55% of cervical biopsies and 24% of endometrial biopsies. High-grade lesions were identified in 21% of follow-up biopsies. In patients with AGC cytology, a positive hrHPV test significantly increased the likelihood of cervical HSIL or above lesions on biopsy by 26.4 times (OR = 26.4, 95% CI: 5.8-119.4, P < 0.0001). A positive genotyping result for HPV 16 dramatically increased the likelihood of cervical HSIL or above lesions on biopsy (OR = 84, 95% CI: 12.0-590.5, P < 0.0001). The HPV test had a negative predictive value of 97% (CI: 85%-100%). CONCLUSIONS: Our study confirms that AGC is a significant diagnosis with an overall risk for high-grade cervical or endometrial lesions as high as 21%. hrHPV testing with genotyping is an effective tool for identifying high-risk individuals within the AGC population, with excellent positive and negative predictive values. This approach is valuable for clinical risk stratification and differential diagnosis in patients with AGC cytology.

Interstitial cystitis: another IgG4-related inflammatory disease?

Interstitial cystitis (IC) is a disease of undetermined etiology and pathogenesis. Inflammation is thought to play a key role in many patients, characteristically with an increase in mast cells within the detrusor muscle of the bladder. We observed that some patients with IC had prominent plasma cells in bladder tissue, which elicited our interest in their possible pathogenic role in patients with IC. A total of 44 cases of IC were collected, including 42 bladder biopsies and 2 cystectomies. Patient age ranged from 18 to 92 years (average age of 49.5 years) and included 7 male and 37 female patients. The histology and immunostains for IgG, IgG4 and tryptase were examined, and the results were correlated with clinical and cystoscopic findings. Four cases showed a significant increase in IgG4-positive plasma cells, with greater than 30 IgG4 plasma cells per high-power field and an IgG4/IgG ratio greater than 0.5. In addition, statistically significant differences were found between IC with IgG4-positive plasma cells vs IgG4-negative cases. The IgG4-positive patients were of older age and had increased severe inflammation and decreased bladder capacity as compared with the IgG4-negative patients. We propose that a subset of patients with IC may have an IgG4-related disease, and further study including serum IgG4 measurement is required to better define this relationship.

Cell pellet from fixative medium of transbronchial lung biopsy sample improves lung cancer ancillary test.

OBJECTIVES: Lung cancer tissue obtained using small biopsies are relatively fragile, leaving behind some tiny tissue fragments or cell clusters in the fixative medium that are difficult to collect for processing as a paraffin-embedded tissue block. Usually, the cellular component of the residual fixative medium is discarded as medical waste as per routine laboratory protocol. No protocol exists for utilizing the cellular component of the residual fixative medium after processing the tissue blocks to improve lung cancer ancillary testing. This study aimed to undercover the potential value of these samples for lung cancer diagnosis and targeted therapy development. MATERIALS AND METHODS: A protocol was developed for cell pellet sample collection from the residual fixative medium of a transbronchial forceps lung biopsy sample. Tumour cell number and fraction in a paired cell pellet and matching formalin-fixed paraffin-embedded tissue section were evaluated from 324 non-smallcell lung carcinoma (NSCLC) cases. We defined the adequacy of the cell pellet for molecular analysis as ≥ 200 tumour cells and ≥ 10 % tumour cells. Real-time polymerase chain reaction and next-generation sequencing were performed on adequate cell pellet samples. RESULTS: We discovered that the fixative medium of most transbronchial forceps lung biopsy samples was enriched in tumour cells. Among 324 biopsy samples, 70 (21.6%) exhibited inadequate formalin-fixed paraffin-embedded tissue sections, whereas 53 (75.7%) yielded adequate cell pellet samples. Somatic mutations detected in the formalin-fixed paraffin-embedded tissue section samples were also detected in the matching cell pellets. CONCLUSIONS: Cell pellets collected from the fixative medium of thoracic small biopsies are a beneficial supplemental material for ancillary testing. Combined use of cell pellets with traditional tissue-based samples can enhance the detection rate of informative mutations in patients with advanced NSCLC.

p16(INK4a) and ProEx C immunostains facilitate differential diagnosis of hyperchromatic crowded groups in liquid-based Papanicolaou tests with menstrual contamination.

OBJECTIVE: Evaluation of hyperchromatic crowded groups in Papanicolaou (Pap) tests from women during menstruation can be a diagnostic pitfall due to similar morphological appearances with significant cervical lesions. We studied the results of p16(INK4a) and ProEx C on cell blocks from Pap tests during menstruation in an attempt to facilitate the differentiation. STUDY DESIGN: Immunohistochemical stains for p16(INK4a) and ProEx C were performed on 25 cell blocks prepared from residual liquid-based cervical material with menstrual contamination. RESULTS: Strong, diffuse, and full thickness staining pattern for p16(INK4a) and ProEx C was observed in cases of high-grade squamous intraepithelial lesion (HSIL) and small cell carcinoma of the cervix. The low-grade squamous intraepithelial lesion cases and cases negative for intraepithelial lesion or malignancy were negative for ProEx C, with focal staining for p16(INK4a). The benign endometrial cells had either negative or focal patchy staining, which is often associated with tubal metaplasia. CONCLUSION: p16(INK4a) and ProEx C are sensitive markers for identifying significant lesions in Pap test specimens with menstrual contamination. Patchy/mosaic staining may be seen in benign endometrial tissue with tubal metaplasia, but strong, diffuse staining likely indicates HSIL or carcinoma. These findings can be helpful in interpreting hyperchromatic crowded groups in menstrual Pap specimens. Further study may be prudent, being aware of the small study group.

Classification of cervical biopsy free-text diagnoses through linear-classifier based natural language processing.

Routine cervical cancer screening has significantly decreased the incidence and mortality of cervical cancer. As selection of proper screening modalities depends on well-validated clinical decision algorithms, retrospective review correlating cytology and HPV test results with cervical biopsy diagnosis is essential for validating and revising these algorithms to changing technologies, demographics, and optimal clinical practices. However, manual categorization of the free-text biopsy diagnosis into discrete categories is extremely laborious due to the overwhelming number of specimens, which may lead to significant error and bias. Advances in machine learning and natural language processing (NLP), particularly over the last decade, have led to significant accomplishments and impressive performance in computer-based classification tasks. In this work, we apply an efficient version of an NLP framework, FastText™, to an annotated cervical biopsy dataset to create a supervised classifier that can assign accurate biopsy categories to free-text biopsy interpretations with high concordance to manually annotated data (>99.6%). We present cases where the machine-learning classifier disagrees with previous annotations and examine these discrepant cases after referee review by an expert pathologist. We also show that the classifier is robust on an untrained external dataset, achieving a concordance of 97.7%. In conclusion, we demonstrate a useful application of NLP to a real-world pathology classification task and highlight the benefits and limitations of this approach.

Clinicopathologic and immunohistochemical characteristics of adult primary cardiac angiosarcomas: analysis of 10 cases.

Primary cardiac angiosarcoma is a rare but the most common malignant neoplasm of the heart in adults. The objective of this study is to analyze the clinicopathologic characteristics of primary cardiac angiosarcoma. Ten cases of primary cardiac angiosarcoma treated in a single institution were analyzed for their clinical, pathologic, and immunohistochemical features. There were 6 men and 4 women, with a mean age of 40 years (range, 20-61 years). The patients commonly presented with dyspnea and distant metastasis. All tumors were located in the right atrium, with a mean tumor size of 6.8 cm. Tumors were hemorrhagic, with variegated tan-brown solid areas. Histologically, they exhibited high-grade morphology with mixed solid growth and anatomizing channels. Frequent mitoses and tumor necrosis were common. The tumors were strongly positive for CD31, CD34, FLI-1, and WT-1 but negative for AE1/3, D2-40, human herpesvirus 8, and epidermal growth factor receptor. The tumor cells were focally reactive to p53, with a high rate of Ki-67 expression. A complete tumor resection was not possible in any of the patients because of the size or extensive local invasion of the tumor. Overall survival ranged from 1 to 81 months (mean, 26.6 months) after initial histologic diagnosis. Primary cardiac angiosarcomas are rare tumors that commonly arise in the right atrium. The mean age is much younger than that of soft tissue angiosarcoma. Regional tumor extension and distant metastasis are extremely common at the time of diagnosis. Surgical resection with adjuvant chemotherapy is currently the preferred treatment, and survival time appears to be inversely correlated with the tumor size and degree of regional tumor extension at the time of surgery.

Assessment of State and Federal Health Policies for Opioid Use Disorder Treatment During the COVID-19 Pandemic and Beyond.

IMPORTANCE: Federal and state governments implemented temporary strategies for providing access to opioid use disorder (OUD) treatment during the COVID-19 pandemic. Advocates hope many of these policies become permanent because of their potential to expand access to care. OBJECTIVE: To consider the multitude of ways access to and utilization of treatment for individuals with OUD might have been expanded by state and federal policy so researchers can do a better job evaluating the effectiveness of specific policy approaches, which will depend on the interaction with other state policies. EVIDENCE REVIEW: We summarize state-level policy data reported by government and nonprofit agencies that track health care regulations, specifically the Kaiser Family Foundation, Federation of State Medical Boards, American Association of Nurse Practitioners, American Academy of Physician Assistants, and the National Safety Council. Data were collected by these sources from September 2020 through January 2021. We examine heterogeneity in policy elements adopted across states during the COVID-19 pandemic in 4 key areas: telehealth, privacy, licensing, and medication for opioid use disorder. The analysis was conducted from March 2020 through January 2021. FINDINGS: This cross-sectional study found that federal and state governments have taken important steps to ensure OUD treatment availability during the COVID-19 pandemic, but few states are comprehensive in their approach. Although all states and Washington, DC have adopted at least 1 telehealth policy, only 17 states have adopted telehealth policies that improve access to OUD treatment for new patients. Furthermore, only 9 states relaxed privacy laws, which influence the ability to use particular technology for telehealth visits. Similarly, all states have adopted at least 1 policy related to health care professional licensing permissions, but only 35 expanded the scope of practice laws for both physician assistants and nurse practitioners. Forty-four states expanded access to initiation and delivery of medication for OUD treatment. Together, no state has implemented all of these policies to comprehensively expand access to OUD treatment during the COVID-19 pandemic. CONCLUSIONS AND RELEVANCE: With considerable policy changes potentially affecting access to treatment and treatment retention for patients with OUD during the pandemic, evaluations must account for the variation in state approaches in related policy areas because the interactions between policies may limit the potential effectiveness of any single policy approach.

Immunohistochemical characterization of subtypes of male breast carcinoma.

INTRODUCTION: Male breast cancer accounts for around 1% of all breast cancer cases but the incidence has risen in recent years. This study aimed to classify the molecular subtypes of male breast cancers based on the expression profile of immunomarkers and to evaluate their association with clinicopathological features and expression patterns of epidermal growth factor receptor (EGFR) and nuclear factor kappaB (NF-kappaB). METHODS: A total of 42 cases of male breast carcinoma were examined retrospectively using immunostains for estrogen receptor (ER), progesterone receptor (PR), cytokeratin 5/6 (CK5/6), EGFR, and NF-kappaB. Human epidermal growth factor receptor 2 (HER2) expression was evaluated by immunostaining and confirmed by fluorescent in situ hybridization (FISH). RESULTS: The luminal A subtype was the most common subtype in male breast cancer (83%, 35/42), which was followed by the luminal B subtype (17%, 7/42). Basal-like and HER2+/ER- subtypes were not identified in this group. All carcinomas expressed ER and 67% of them were PR+. High nuclear grades were more common in the luminal B subtype (71%, 5/7) than in the luminal A subtype (34%, 12/35). The luminal B subtype carcinomas expressed EGFR (42%, 3/7) and NF-kappaB (57%, 4/7) more frequently than the luminal A subtype did (17%, 6/35 and 37%, 13/35, respectively). CONCLUSIONS: In our study group, luminal A and B subtypes were the major subtypes of male breast carcinoma. The immunophenotypical features of male breast cancer differ from those of its female counterpart. Luminal B subtype tended to have high nuclear grade and more frequent expression of EGFR and NF-kappaB.

Thyrolipoma and thyrolipomatosis: 5 case reports and historical review of the literature.

Because thyrolipoma (adenolipoma of thyroid) and thyrolipomatosis (diffuse lipomatosis of thyroid) are distinctively rare conditions with only few cases reported in the literature, we are reporting 5 additional cases. All the 5 patients were adult females, with ages from 38 to 79 years, who presented with thyroid masses. Four of the patients had normal thyroid function tests and one had mild hypothyroidism. All patients received partial or total thyroidectomy. The thyroid specimens showed either circumscribed yellow-tan masses (cases 1, 2, and 3) or diffuse yellow-brown discoloration (cases 4 and 5). Histologic examination revealed abundant mature fat infiltrating the affected thyroid tissue in 3 distinct patterns: (1) fat infiltration limited to follicular adenomas (thyrolipoma); (2) fat diffusely infiltrating throughout the thyroid gland (thyrolipomatosis); or (3) fat infiltration involving both follicular adenoma and their surrounding thyroid tissue. Because of the rarity of thyroid fat-containing lesions, confusion in differential diagnosis may occasionally occur. It is important to be aware during frozen section that these lesions may present as extrathyroidal nodules, which can be radioactive on intraoperative scan for parathyroid glands. In addition, a papillary thyroid carcinoma was also identified in one case of thyrolipomatosis. All patients recovered well after surgery and there has been no recurrence of the lesions after 1 to 24 years of clinical follow-up. In summary, we are reporting 5 rare cases of thyrolipoma and thyrolipomatosis with distinct histologic patterns. Previously reported cases of thyrolipomatosis were reviewed and analyzed with the current cases.

Age-specific 3-year cumulative risk of cervical cancer and high-grade dysplasia on biopsy in 9434 women who underwent HPV cytology cotesting.

BACKGROUND: High-risk human papillomavirus (HPV)-Papanicolaou (Pap) cotesting is recommended for cervical cancer screening in women aged ≥30 years. The current study analyzed the effectiveness of cotesting on risk management in different age groups. METHODS: A retrospective review of a 5-year cytology database identified 9434 women with HPV-Pap cotesting and follow-up cervical biopsy. The 3-year cumulative risk of developing high-grade cervical lesions (≥high-grade squamous intraepithelial lesion [HSIL]) was analyzed using age stratification. RESULTS: The 3-year cumulative risk of developing ≥HSIL was found to be significantly different in women with baseline cotesting HPV-positive and Pap-positive results (HPV+/Pap+; defined as ≥atypical squamous cells of undetermined significance), HPV+ and Pap-negative results, and HPV-negative and Pap+ results at 19.2%, 7.9%, and 3.1%, respectively (P < .001). The risk of ≥HSIL peaked at ages 30 to 39 years and significantly decreased at ages 50 to 59 years (16.6% vs 6.7%; P < .001). Women aged <30 years shared a high risk similar to that of women aged 30 to 39 years (17.3% vs 16.6%; P = .52), and risk stratification by cotesting was found to be equally effective in the younger age group (HPV+ and Pap+: 19.6%; HPV+ and Pap-negative: 7.2%; and HPV-negative and Pap+: 4.4% [P < .001]). CONCLUSIONS: High-risk HPV-Pap cotesting appears to be extremely sensitive for the prediction of the risk of developing ≥HSIL and is an effective tool for risk stratification. In the current study, the 3-year cumulative risk of developing ≥HSIL varied significantly with age, with the highest risk noted among women aged <40 years and the lowest risk observed in women aged 50 to 59 years. Pap testing significantly impacted risk stratification in the HPV+ positive group, especially in women aged <60 years. Women aged <30 years were found to have a risk profile and cotesting efficacy similar to those of women aged 30 to 39 years. Modification of the current recommendation to offer cotesting to women aged ≥30 years might be considered to include those patients aged <30 years.

HPV status in women with high-grade dysplasia on cervical biopsy and preceding negative HPV tests.

INTRODUCTION: A considerable number of patients with high-grade cervical lesions have undergone preceding human papillomavirus (HPV) tests with negative results. In the present study, we attempted to elucidate the factors potentially contributing to the findings by testing biopsied samples from these patients. MATERIALS AND METHODS: Of the 1654 women with HPV testing and follow-up cervicovaginal biopsies from March 1, 2013 to June 30, 2014, 21 of 252 women (8.3%) with biopsy-confirmed high-grade squamous intraepithelial lesion (HSIL) or worse had had negative results from preceding high-risk (hr)HPV tests. The corresponding paraffin blocks were tested for HPV using the Cobas 4800 system, a DNA microarray against 40 HPV genotypes, and DNA sequencing. RESULTS: HPV was detected in 20 (95%) of the 21 biopsies with HSIL or worse, including HPV16/18 in 4, non-16/18 hrHPV in 10, and non-hrHPV in 6. HPV59 and HPV45 were 2.2 times more frequently detected than HPV16/18 in these samples. One sample was negative for all 3 tests (5%). CONCLUSIONS: Our study has demonstrated that 8.3% of women with biopsy-confirmed HSIL or worse had preceding test results that were negative for hrHPV. The vast majority of the biopsied samples had detectable HPV, primarily hrHPV genotypes (67%) with HPV59 and HPV45 predominance. This genotypic prevalence pattern was markedly different from those reported in the general population. Non-hrHPV genotypes contributed to 29% of the cases, and HPV-negative cases were rare. In addition to the limited Cobas testing panel and rare possible HPV-negative HSIL or worse, other possible contributing factors to the discrepancy include cytologic sampling, interference material, technical errors, and reduced L1 gene expression in high-grade lesions.

Performance of Roche cobas high-risk human papillomavirus (hrHPV) testing in the two most common liquid-based Papanicolaou test platforms.

INTRODUCTION: High-risk human papillomavirus (hrHPV) testing is important in cervical cancer screening and management algorithms. Roche (Pleasanton, Calif.) cobas hrHPV testing is commonly performed on both ThinPrep (TP) and SurePath (SP) samples, but performance of these platforms has not been fully investigated in the literature. MATERIALS AND METHODS: Roche hrHPV testing was performed on 47,885 (TP = 18,295; SP = 29,590) out of 130,648 consecutive Papanicolaou tests, over 16 months; 1895 of those had interpretable biopsies. RESULTS: The overall hrHPV detection rates were similar in TP (13.5%) and SP (13.1%). The hrHPV positive rate was higher in SP (8.5%) than TP (7.3%, P < 0.0001) in women with negative cytology; the difference in other cytologic diagnosis categories was insignificant. TP samples had significantly fewer negative cytology diagnoses (7.3% versus 8.5%, P < 0.0001), more low-grade abnormalities in cytology and biopsies, and higher colposcopy referral rate (4.8% versus 2.7%, P < 0.0001) than SP. There were no differences between TP and SP in detecting ≥HSIL by hrHPV testing, cytology or biopsy. SP samples had a significantly higher rate of HPV 16/18 but a lower rate of non-16/18 hrHPV genotypes than TP. CONCLUSIONS: Roche cobas hrHPV testing was similar in both TP and SP platforms. The significantly lower hrHPV detection rate in cytological negative TP samples is likely related to higher cytology reporting rates for indeterminate and low-grade diagnoses in TP than SP samples. Significant differences were also observed in hrHPV genotyping results between TP and SP. Clinical risk stratification based on hrHPV testing may need to take testing platforms into consideration.