Use of Uterine Characteristics to Improve Fertility-Sparing Diagnosis of Adenomyosis.

Objective: To describe patient demographics, determine accuracy of clinical diagnosis, and evaluate reliability of laparoscopic uterine characteristics in the diagnosis of adenomyosis. Materials and Methods: Enrollment included 117 patients undergoing laparoscopic hysterectomy for benign indications. Intraoperatively, the attending surgeon predicted uterine weight; evaluated the presence of fibroids; and commented on the uterus' shape, color, and consistency while probing it with a blunt instrument. A prediction was also made about whether final pathology would reveal adenomyosis. Standardized video recordings were obtained at the start of the case. Each video was viewed retrospectively twice by three expert surgeons in a blinded fashion. Uterine characteristics were reported again with a prediction of whether or not there would be a pathologic diagnosis of adenomyosis. These data were used to calculate inter-and intrarater reliability of diagnosis. Results: Women with adenomyosis were more likely to complain of midline pain as opposed to lateral or diffuse pain (p = 0.048) with no difference in the timing of the pain (p = 0.404), compared to patients without adenomyosis. Uterine tenderness on examination was not an accurate predictor of adenomyosis (p = 0.566). Preoperative diagnosis of adenomyosis by clinicians was poor, with an accuracy rate of 51.7%. None of the intraoperative uterine characteristics were significant for predicting adenomyosis on final pathology, nor was any combination of the features (p = 0.546). Retrospective video reviews failed to reveal any uterine characteristics that generated consistent inter- or intrarater reliability (Krippendorff's α < 0.7) in making the diagnosis of adenomyosis. Conclusions: Clinical and video diagnosis of adenomyosis have low accuracy with no uterine characteristics consistently or reliably predicting adenomyosis on final pathology. (J GYNECOL SURG 34:183).

Point-Counterpoint: Cervical Cancer Screening Should Be Done by Primary Human Papillomavirus Testing with Genotyping and Reflex Cytology for Women over the Age of 25 Years.

Screening for cervical cancer with cytology testing has been very effective in reducing cervical cancer in the United States. For decades, the approach was an annual Pap test. In 2000, the Hybrid Capture 2 human papillomavirus (HPV) test was approved by the U.S. Food and Drug Administration (FDA) for screening women who have atypical squamous cells of underdetermined significance (ASCUS) detected by Pap test to determine the need for colposcopy. In 2003, the FDA approved expanding the use of the test to include screening performed in conjunction with a Pap test for women over the age of 30 years, referred to as "cotesting." Cotesting allows women to extend the testing interval to 3 years if both tests have negative results. In April of 2014, the FDA approved the use of an HPV test (the cobas HPV test) for primary cervical cancer screening for women over the age of 25 years, without the need for a concomitant Pap test. The approval recommended either colposcopy or a Pap test for patients with specific high-risk HPV types detected by the HPV test. This was based on the results of the ATHENA trial, which included more than 40,000 women. Reaction to this decision has been mixed. Supporters point to the fact that the primary-screening algorithm found more disease (cervical intraepithelial neoplasia 3 or worse [CIN3+]) and also found it earlier than did cytology or cotesting. Moreover, the positive predictive value and positive-likelihood ratio of the primary-screening algorithm were higher than those of cytology. Opponents of the decision prefer cotesting, as this approach detects more disease than the HPV test alone. In addition, the performance of this new algorithm has not been assessed in routine clinical use. Professional organizations will need to develop guidelines that incorporate this testing algorithm. In this Point-Counterpoint, Dr. Stoler explains why he favors the primary-screening algorithm, while Drs. Austin and Zhao explain why they prefer the cotesting approach to screening for cervical cancer.

Brush cytology of the fallopian tube and implications in ovarian cancer screening.

STUDY OBJECTIVE: To determine whether fallopian tube epithelial cells adequate for cytopathology can be obtained via a minimally invasive approach using brush cytology. DESIGN: Prospective feasibility study (Canadian Task Force classification II-1). SETTING: Tertiary-care university-based teaching hospital. PATIENTS: Ten patients who underwent laparoscopic hysterectomy, with or without adnexal surgery, because of benign indications. INTERVENTIONS: Attempted hysteroscopic and laparoscopic brush cytologic sampling of the fallopian tubes. MEASUREMENTS AND MAIN RESULTS: ThinPrep slides and cell blocks were prepared and analyzed. P53 and KI-67 immunostaining was performed on cell block specimens if adequate cellularity was present. The first 5 patients underwent attempted hysteroscopic sampling of the fallopian tube, with successful collection only in 1 patient. The protocol was then modified to enable sampling of the fallopian tube laparoscopically as well as hysteroscopically. In the other 5 patients sampling of the fallopian tubes was successful laparoscopically, including successful sampling hysteroscopically in 1 patient. The brush biopsy catheter could not be passed through the entire length of the fallopian tube in either the hysteroscopic or laparoscopic approach. All cytologic findings were interpreted as benign, although findings of nuclear overlapping, crowding, and small nucleoli were initially considered benign atypia. Immunohistochemistry for P53 and KI-67 yielded uniformly negative findings. CONCLUSION: To our knowledge, this is the first study to describe endoscopic brush cytology of the fallopian tubes with correlated cytologic narrative. In the future, cytologic sampling of the fallopian tube may have implications for an ovarian cancer screening test.

Cytologic findings in experimental in vivo fallopian tube brush specimens.

OBJECTIVE: The fallopian tube is now recognized as a primary source of precursor neoplastic lesions for pelvic serous adenocarcinomas. Cytologic features of fallopian tube brushings from low-risk patients have not been well described. STUDY DESIGN: We describe the cytomorphology of tubal epithelium from prospectively collected experimental in vivo brushings from normal fallopian tubes of 7 low-risk patients. Liquid-based cytology slides and cell blocks were prepared and reviewed on all specimens. RESULTS: Fifteen brush cytology specimens were obtained, ten by laparoscopy, four by hysteroscopy and one following hysterectomy and bilateral salpingo-oophorectomy on an ex vivo specimen. Variable cytologic features were documented for background, cellularity, cellular architecture, cilia, nuclear overlap, mitoses, nuclear pleomorphism, nuclear membrane changes and nucleoli. Negative P53 and Ki-67 stain results were documented in available cell blocks. Histopathologic salpingectomy findings and clinical follow-up were benign. CONCLUSION: Moderate nuclear pleomorphism and nuclear overlap, prominent single and multiple nucleoli and background granular debris were common challenging cytologic findings in fallopian tube brushings from low-risk patients. With experience, cellular changes can be recognized as benign. Recognition of the range of normal fallopian tube cytology should help to minimize false-positive interpretations of cytology specimens obtained in association with risk-reducing salpingo-oophorectomies.

Histopathologic outcomes and clinical correlations for high-risk patients screened with anal cytology.

OBJECTIVE: Anal cytologic testing is being increasingly used as a preventive screening test in high-risk populations. We document anal cytology results, correlating HIV test results, and histopathologic follow-up outcomes from a large integrated health system which recently implemented anal screening. STUDY DESIGN: Anal Pap tests between May 2007 and August 2009 were studied and correlated with HIV test histories and follow-up histopathologic diagnoses. RESULTS: 688 anal cytologic tests were identified with 7.4% reported as unsatisfactory; 72% of anal cytologic tests were abnormal; 91% of patients were HIV positive. The HIV-positive rate and likelihood of high viral load were both significantly greater among patients with abnormal anal cytology than among patients with negative anal cytology, but did not vary significantly among patients with different categories of abnormal anal cytology. For 459 patients with abnormal anal cytology, 198 had anal biopsies. For patients with abnormal anal cytology findings of ASC-US (atypical squamous cells of undetermined significance), LSIL (low-grade squamous intraepithelial neoplasia), ASC-H (atypical squamous cells, cannot exclude high-grade squamous lesion), and HSIL (high-grade squamous intraepithelial neoplasia), histopathologic intraepithelial neoplasia (AIN)2/3 or 2/3+ diagnoses were established in 46.5, 56.6, 65, and 80.8%, respectively. CONCLUSIONS: Patients with any level of abnormal anal cytology result are at significant risk of the presence of histopathologically verifiable high-grade anal intraepithelial lesions. More specific markers for identifying patients at highest risk of progression to invasive anal carcinoma are needed.

Heavy cervical cancer burden in elderly women: how can we improve the situation?

OBJECTIVES: The American Cancer Society, the American College of Obstetricians and Gynecologists and the US Preventive Services Task Force recommend discontinuation of cervical cancer screening between 65 and 70 years of age in women with no abnormal test results in the preceding 10 years. This population-based study was undertaken to determine the incidence of cervical cancer in different age groups as a means to establish if current screening recommendations need reevaluation. STUDY DESIGN: Data from the SEER database were used to compute incidence rates for cervical cancer diagnosed between 2000 and 2006 by age and disease stage. RESULTS: We identified 18,003 women with cervical cancer. 12.18% were above the age of 69. The incidence in this age group was 8.7/100,000. Women younger than 30 comprised 5.7% of patients with an incidence of 5/100,000 and were most commonly diagnosed with stage IA1 disease. Women above 70 were most frequently diagnosed with stage IIIB. 79% of patients younger than 30 were diagnosed with an early disease (stage IA1-IIA) as opposed to only 41.2% of patients aged 69 or above. CONCLUSIONS: The incidence of cervical cancer does not decrease significantly in older women. Women over the age of 70 are frequently diagnosed with advanced stage disease which limits their treatment options. Failure to apply uniform screening across all at-risk age groups may account for the discrepancy.

Change of Practice Patterns Following an Educational Comment on Reports of Benign-Appearing Endometrial Cells in Papanicolaou Tests.

OBJECTIVES: Since the publication of our study demonstrating high negative predictive values (>99% for women in their 40s) of benign-appearing endometrial cells (nEMCs), we have begun to include an educational comment in Papanicolaou (Pap) test reports with nEMCs that recommends routine periodic screening for asymptomatic premenopausal women (APW). The current study evaluated how the inclusion of this comment has affected clinical practice patterns at our institution. METHODS: The 2017 to 2019 database identified 175 reports containing the educational comment in women aged 45 to 54 years with a follow-up time of 11 to 37 months. Data, including age, menopause status, symptoms, imaging, and outcome, were collected. The procedure rate and the impact of clinical modifiers were assessed. RESULTS: Thirty-seven (20.6%) patients had biopsies within 6 months, which decreased from 48.1% as we previously reported. All nine (5%) APW with biopsies triggered only by nEMCs had benign histopathology. The remaining 28 biopsied patients had abnormal bleeding or a thickened endometrium, or they were postmenopausal, including a 53-year-old patient with complex atypical hyperplasia. None of the 138 patients with conservative follow-up developed atypical/malignant lesions. CONCLUSIONS: A qualifying educational note included in Pap reports significantly reduced follow-up biopsies in APW. Optimal follow-up of nEMCs should be based on relevant clinical modifiers.

Nationwide Prevalence and Genotype Distribution of High-Risk Human Papillomavirus Infection in China.

OBJECTIVES: Extended high-risk human papillomavirus (hrHPV) genotype testing has recently been introduced in routine cervical cancer screening. Changes in national and regional hrHPV genotype prevalence offer an objective baseline indicator of the future impact of mass HPV vaccination and HPV-based cervical screening. METHODS: This retrospective study reports nationwide hrHPV genotyping results from July 2018 to June 2019 in 29 KingMed Diagnostics laboratories throughout China. RESULTS: In total, 2,458,227 hrHPV genotyping results were documented from KingMed's nationwide laboratory database during the study period. The overall prevalence of hrHPV-positive results was 19.1%, with twin peaks for highest hrHPV infection rates in women younger than 30 years of age (22.0%) and 50 years of age and older (21.8%). The most frequently detected hrHPV genotypes were HPV-52 (4.7%), HPV-16 (3.4%), HPV-53 (2.5%), HPV-58 (2.4%), HPV-51 (2.0%), and HPV-68 (1.6%). Overall, hrHPV-positive results varied regionally from 15.3% to 24.4%. CONCLUSIONS: Nationwide hrHPV genotyping results from KingMed laboratories offer a baseline for measuring the future impact of large-scale HPV vaccination. High hrHPV infection rates in older (≥50 years) Chinese women likely reflect the limited extent of cervical screening in China. High rates of hrHPV infection and variable regional hrHPV genotype distribution may represent limiting factors for cost-effective implementation of hrHPV-based cervical screening in China.

The Clinical Utility of Extended High-Risk HPV Genotyping in Women With ASC-US Cytology.

OBJECTIVES: Extended testing for high-risk human papillomavirus genotypes (hrHPVGTs) is increasingly investigated for risk stratification in cervical cancer screening. METHODS: Age and hrHPVGT results from 16,993 women with atypical squamous cells of undetermined significance (ASC-US) cytology between November 2015 and August 2021 were studied and correlated with available histopathologic findings within 6 months. RESULTS: High-risk human papillomavirus (hrHPV)-positive rate was 66.9% in women with ASC-US cytology, and the most prevalent genotypes were HPV 52 (20.9%), 16 (15.7%), and 58 (12.8%). Single hrHPV genotypes and multiple HPV genotypes were detected in 77.2% and 22.8% of women with hrHPV-positive results. Cervical intraepithelial neoplasia grade 2 or more (CIN2+) severe lesions were identified in 19.5% of women with hrHPV-positive ASC-US. The greatest risk for CIN2+ was found in single genotype infections with HPV 16 (33.1%), followed by women with multiple genotype infections, including HPV 16 (32.7%), 82 (30.8%), and 31 (30.0%). hrHPVGT testing for genotypes 16, 31, 35, 45, 82, 58, 33, 52, and 18 was identified in 91.9% (965/1,050) of CIN2+ cases, with 88.9% sensitivity, 43.2% specificity, positive predictive value of 23.9%, and negative predictive value of 95.1%. CONCLUSIONS: Extended hrHPV genotyping for women with ASC-US cytology could identify those hrHPV genotypes (HPV 16, 31, 35, 45, 82, 58, 33, 52, 18) associated with higher risk of CIN2+ and allows for refined risk stratification of women being screened.

Risk stratification for cervical neoplasia using extended high-risk HPV genotyping in women with ASC-US cytology: A large retrospective study from China.

BACKGROUND: Extended high-risk human papillomavirus (hrHPV) genotype testing (hrHPVGT) has emerged as a new strategy to help optimize the efficiency of hrHPV triage. METHODS: Women with an atypical squamous cells of undetermined significance (ASC-US) cervical Papanicolaou test result who underwent hrHPVGT between October 2017 and May 2021 at the Obstetrics and Gynecology Hospital of Fudan University in Shanghai, China, were studied. For hrHPVGT, a proprietary multiplex real-time polymerase chain reaction assay was used. hrHPVGT and viral load test results in selected patients were correlated with histopathologic follow-up findings available within 6 months. RESULTS: In total, 17,235 women with ASC-US cytology who had hrHPVGT results were identified in the Obstetrics and Gynecology Hospital of Fudan University database. The hrHPV-positive rate was 61.8%, and the most prevalent hrHPV genotypes were type 52 (HPV52) (16%), HPV16 (11.3%), HPV58 (10.2%), and HPV53 (8.4%). Single hrHPV genotypes were detected in 65.9% of women with hrHPV-positive results, and multiple genotypes were detected in 34.1%. Histopathologic cervical findings within 6 months were available in 5627 hrHPV-positive women and 2223 hrHPV-negative women. High-grade cervical intraepithelial lesions or cervical cancer (cervical intraepithelial neoplasia 2 or greater [CIN2+]) were identified in 7.5% of hrHPV-positive women who had ASC-US cytology and in 0.9% of hrHPV-negative women who had ASC-US cytology. The greatest risk for CIN2+ was in single hrHPV genotype infections with HPV16 (21.1%), HPV33 (15.2%), HPV82 (10%), and HPV18 (9.9%). hrHPVGT for genotypes HPV16, HPV33, HPV82, HPV18, HPV31, HPV45, HPV58, and HPV52 identified 95% of CIN2+ cases with 90.8% sensitivity, 53.8% specificity, a positive predictive value of 10.2%, and a negative predictive value of 99%. A significantly increased viral load was associated only with women who had HPV16-related CIN2+. CONCLUSIONS: hrHPVGT for women who have ASC-US cytology allows for risk stratification capable of optimizing the efficiency of triage for hrHPV-positive women.

Follow-up outcomes for a large cohort of US women with negative imaged liquid-based cytology findings and positive high risk human papillomavirus test results.

OBJECTIVE: This study aimed to follow a large group of US women with negative computer-imaged liquid-based cytology (LBC) and positive high risk (hr) HPV DNA results. METHODS: Negative LBC and positive hrHPV cases were identified between July 1, 2005 and December 31, 2009. Cytologic and histopathologic follow-up results, repeat HPV results, and prior history were analyzed. RESULTS: 1099 Patients with negative LBC and positive hrHPV results were identified. Eight hundred sixty-nine had repeat Pap or histopathologic follow-up results. Average age was 41.2 years. Average follow-up was 23.2 months. Two hundred ninety of 869 had colposcopic examination and biopsies, including 33 diagnostic excisional procedures and 10 hysterectomies. Cervical intraepithelial neoplasia (CIN) 1 and low-grade squamous intraepithelial lesions (CIN1/LSIL) and more severe lesions (CIN1/LSIL+) were detected in 211 of 689 (24.3%). CIN2+ was diagnosed in 21 (2.4%) (1 VAIN3, 2 adenocarcinoma in situ, 1 invasive cervical adenocarcinoma). Six hundred six had repeat HPV tests and 200 had multiple repeat HPV tests. More LSIL/CIN1+ was identified with repeat positive HPV results than with repeat negative HPV results (P<0.001). LSIL/CIN1+ was detected more often with a history of LSIL/CIN1+ than with a history of negative Paps (P<0.001). Eight of 105 (7.6%) cytology-negative HPV-positive patients tested positive for HPV 16 and/or HPV 18. CONCLUSION: This is the largest study documenting follow-up on US cytology-negative hrHPV-positive patients screened with now widely utilized FDA-cleared methods of ciLBC and hrHPV testing. Of 869 patients followed for an average of almost 2 years, 20 cases of high grade intraepithelial neoplasia (2.3%) and one case of endocervical adenocarcinoma were detected. 90.5%(190/210) of intraepithelial neoplasias detected during follow-up were CIN1.

HPV test results stratify risk for histopathologic follow-up findings of high-grade cervical intra-epithelial neoplasia in women with low-grade squamous intra-epithelial lesion Pap results.

OBJECTIVE: Age-adjusted evaluations have explored the possible utility of human papillomavirus (HPV) test results in women with low-grade squamous intra-epithelial lesion (LSIL) Paps. We document LSIL correlation data with HPV test results and histopathologic follow-up from a large academic women's hospital practice. STUDY DESIGN: LSIL Pap tests with intermediate-/high-risk HPV DNA testing between July 1, 2005 and April 30, 2008 were studied along with follow-up histopathologic diagnoses. Patients were divided into age groups, and tissue diagnoses were correlated with HPV test results. RESULTS: 1,083 (80.2%) of a total of 1,351 LSIL Pap samples tested HPV positive. HPV prevalence declined in older age groups. 719 women with LSIL Pap and HPV test results had at least 1 follow-up cervical biopsy result. 89 of 612 patients with HPV-positive LSIL (14.5%) had a follow-up histopathological diagnosis of cervical intra-epithelial neoplasia (CIN) 2/3. Only 4 of 107 patients with HPV-negative LSIL (3.7%) had CIN 2/3. CONCLUSIONS: In the largest study to date to document histopathological follow-up of older women with LSIL and HPV test results, no histopathological CIN 2/3 diagnoses were identified in women 50 years and older with HPV-negative LSIL. HPV test results stratified women with LSIL cytology findings into lower- and higher-risk groups for follow-up histopathologic CIN 2/3 outcomes.

Cytomorphology of crystal storing histiocytosis in the breast associated with lymphoma: a case report.

Crystal storing histiocytosis (CSH) is a very rare immunoglobulin (Ig) deposition disorder in which macrophages accumulate light chains or Ig crystalline inclusions. It is frequently associated with lymphoproliferative disorders, but can be seen in some reactive conditions too. This article reports the cytomorphologic, histopathologic, and ancillary study findings of a marginal zone B cell lymphoma of the breast with CSH in a 54-year-old woman. To the best of our knowledge, this is the first report describing CSH in the breast and one of a few reports describing the cytomorphology of CSH. In breast fine-needle aspiration biopsies, CSH can be confused with benign processes such as fat necrosis and histiocytic lesions. Thus, awareness of this rare entity and its frequent association with lymphoproliferative disorders is useful in order to triage a specimen appropriately and exclude the possibility of a lymphoproliferative process.

Personalized Medicine and Cervical Screening: Development of Individualized Quantitative Risk Assessments for Cervical Adenocarcinoma and Adenocarcinoma in situ.

INTRODUCTION: Cervical screening has decreased the incidence of cervical carcinoma around the world primarily by preventing cervical squamous carcinoma, with significantly less measurable protective benefits in prevention of cervical adenocarcinoma. In this study, we apply Bayesian modeling of cervical clinical, screening, and biopsy data from a large integrated health system to explore the feasibility of calculating personalized risk assessments on screened system patients for subsequent histopathologic diagnoses of invasive cervical adenocarcinoma (AdCa) or cervical adenocarcinoma in situ (AIS). MATERIALS AND METHODS: Diagnoses of cervical AIS or AdCa rendered between 2005 and 2018 were identified in our large health system database with 1,053,713 cytology results, 354,843 high-risk (hr) human papillomavirus (HPV) test results, and 99,012 cervical histopathologic results. Using our continuously updated Bayesian cervical cancer screening model which includes clinical data, cervical screening results, and cervical biopsy results, we projected quantitative estimates of patients' 5-year cumulative risk for cervical AIS or AdCa. RESULTS: 161 patients were identified with AIS (ages 17-75, mean 37 years), and 99 patients had diagnoses of cervical AdCa (ages 26-91, mean 48 years). Quantitative Bayesian 5-year cumulative risk projections for diagnoses of cervical AdCa or AIS in patients with different cervical screening test and biopsy histories were determined. The highest patient risk projections for subsequent cervical AdCa and/or AIS histopathologic diagnoses were associated with prior cervical screening test results of HPV-positive atypical glandular cells. Prior squamous cytologic abnormalities were associated with lower risk estimates. Prior histopathologic diagnoses of squamous abnormalities also influenced quantitative risk. A prior histopathologic diagnosis of AIS was associated with a very low risk of subsequent AdCa, consistent with effective excisional treatment. AdCa risk was greatest in women aged 30-65 years with prior CIN3 biopsy results, whereas AIS risk was greatest in women <30. CONCLUSION: Prevention of cervical AdCa in screened patients remains a major challenge for cervical screening. Individualized risk projections for cervical glandular neoplasia reflecting patient age, prior cervical screening test results, and prior cervical biopsy history are feasible using Bayesian modeling of health system data.

Aptima HPV messenger RNA testing and histopathologic follow-up in women with HSIL cytology: A study emphasizing additional review of HPV-negative cases.

BACKGROUND: High-risk human papillomavirus (hrHPV) messenger RNA (mRNA) testing, the Food and Drug Administration-approved testing platform since 2013, has been increasing as a cervical screening alternative to hrHPV DNA testing methods. This study reports the largest routine clinical follow-up study reported to date of hrHPV mRNA cotesting and histopathologic follow-up results for women with high-grade squamous intraepithelial lesion (HSIL) cytology results. METHODS: HSIL Papanicolaou test results for women cotested with Aptima hrHPV mRNA testing between June 2015 and November 2020 were analyzed along with recorded histopathologic follow-up results within 6 months of screening. RESULTS: Aptima hrHPV mRNA-positive results were reported for 95.2% of the cotested HSIL cytology cases (905 of 951). Histopathologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed on follow-up in 538 of 701 hrHPV mRNA-positive cases (76.8%) and in 15 of 36 hrHPV mRNA-negative cases (41.7%). Additional reviews of the hrHPV mRNA-negative HSIL cases showed variable interpretations, and confirmatory blinded-review interpretations of HSIL or atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion were more likely in cases with histopathologic CIN2+ (77.5% [93 of 120]) than those with cervical intraepithelial neoplasia grade 1 or negative findings (63.1% [101 of 160]; P < .01). CONCLUSIONS: This large routine-clinical-practice study confirms the previously reported high sensitivity of hrHPV mRNA testing for the detection of high-grade cervical dysplasia and cervical cancers. The blinded-review findings indicate that additional cytology review may be helpful for confirming an interpretation of HSIL in daily practice, especially for hrHPV-negative HSIL cases.

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: review of ancillary testing modalities and implications for follow-up.

OBJECTIVE: To review the cytology category atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), with human papillomavirus (HPV) and other ancillary testing results and according to age group. METHODS: A literature search was performed on the ASC-H category, and studies analyzing ASC-H according to ancillary testing modalities or patient age groups during the past 4 years were emphasized. RESULTS: The ASC-H category accounts for less than 1% of cytology reports, and 33% to 84% will test positive for oncogenic HPV. The number of patients with cervical intraepithelial neoplasia 2/3 and cancer on biopsy is quite variable, from about 12% to more than 70%, averaging about 40%. The variation reflects patient population as well as local laboratory practices, but older subgroups are more likely to have negative HPV results and negative follow-up. Both the sensitivity of HPV testing for cervical intraepithelial neoplasia 2/3 detection and the negative predictive value for a patient with ASC-H and negative HPV testing average more than 95%. Additional studies evaluating other types of ancillary testing for the ASC-H category are needed. CONCLUSIONS: Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, is an uncommon cytology result, and HPV testing results and biopsy follow-up show variation according to patient age group and local laboratory practices. A negative HPV result in ASC-H offers a high negative predictive value and could be considered as a management strategy in mature women as well as women 30 years and older receiving combined cytology and HPV screening.

Individualized Bayesian Risk Assessment for Cervical Squamous Neoplasia.

BACKGROUND: Cervical screening could potentially be improved by better stratifying individual risk for the development of cervical cancer or precancer, possibly even allowing follow-up of individual patients differently than proposed under current guidelines that focus primarily on recent screening test results. We explore the use of a Bayesian decision science model to quantitatively stratify individual risk for the development of cervical squamous neoplasia. MATERIALS AND METHODS: We previously developed a dynamic multivariate Bayesian network model that uses cervical screening and histopathologic data collected over 13 years in our system to quantitatively estimate the risk of individuals for the development of cervical precancer or invasive cervical cancer. The database includes 1,126,048 liquid-based cytology test results belonging to 389,929 women. From-the-vial, high risk human papilloma virus (HPV) test results and follow-up gynecological surgical procedures were available on 33.6% and 12% of these results (378,896 and 134,727), respectively. RESULTS: Historical data impacted 5-year cumulative risk for both histopathologic cervical intraepithelial neoplasia 3 (CIN3) and squamous cell carcinoma (SCC) diagnoses. The risk was highest in patients with prior high grade squamous intraepithelial lesion cytology results. Persistent abnormal cervical screening test results, either cytologic or HPV results, were associated with variable increasing risk for squamous neoplasia. Risk also increased with prior histopathologic diagnoses of precancer, including CIN2, CIN3, and adenocarcinoma in situ. CONCLUSIONS: Bayesian modeling allows for individualized quantitative risk assessments of system patients for histopathologic diagnoses of significant cervical squamous neoplasia, including very rare outcomes such as SCC.