Type-specific human papillomavirus prevalence in women referred for colposcopy in Tehran.

Background and Objectives: Although several studies have been achieved on the frequency of the HPV types among women with cervical cancer in Iran, HPV-positive samples were in some cases directed to specific-primer genotyping of HPV 16 and 18. Therefore, the other HPV types are underestimated. Several studies have also reported a greater prevalence of HPV 16 in cervical cancer in Iran than in the world. To clarify these subjects, the distribution of HPV types in women referred for colposcopy in Tehran was investigated. Materials and Methods: In this cross-sectional study, a total of 148 cervical samples from women with normal, atypical squamous cells of undetermined significance, cervical intraepithelial neoplasia I-III, and invasive cervical cancer histopathology were included. HPV was detected by PCR assay and all HPV-positive specimens were subjected to direct nucleotide sequencing. Results: Our results demonstrated that the total prevalence of HPV was 92.5%. The five most common HPV types were HPV 16 (49.3%), 18 (14.8%), 6 (7.4%), 31 (4.1%), and 11 (2.7%). About the histopathological stage, HPV 16 and 18 were dominant in all studied groups. In cervical cancer, HPV 16 and 18 were detected in 60% and 20% of cases, respectively. Conclusion: HPV 16 and 18 were the most common in cervical cancer in Iran.

Genotype profile of HPV in ASC-H cytology and histologic follow-up-prevalence, distribution, and risk: A retrospective study of 1414 cases.

BACKGROUND: A cytologic diagnosis of atypical squamous cells, cannot exclude high-grade squamous lesion (ASC-H) poses a disproportionately high risk of cervical cancer development. The objective of this study was to analyze type-specific risks by mapping human papillomavirus (HPV) genotypes in ASC-H cytology. METHODS: In total, 1,048,581 Papanicolaou tests that had ASC-H cytology were retrieved. Concurrent HPV genotyping using proprietary multiplex real-time (MRT) and polymerase chain reaction (PCR) HPV tests and histologic follow-up findings were analyzed. RESULTS: Among 1678 patients who had ASC-H findings (0.16%), 1414 (84.3%) underwent concurrent HPV genotyping (MRT, 857; HPV PCR test, 557). The overall high-risk HPV (hrHPV)-positive rate was 84.4%. Of the 857 MRT cases, 63.9% were infected with a single hrHPV, and 24.4% had multiple genotypes. The most prevalent HPV types were HPV16/52/58/33/31. Lesions that were identified as cervical intraepithelial neoplasia 2 or worse (CIN2+) were detected in 498 of 906 cases (55.0%), including 81 cervical carcinomas (8.9%). The risk of CIN2+ for the composite group of HPV16/52/58/33/31-positive cases was 62.7%, representing 90.7% (264 of 291) of total CIN2+ lesions in ASC-H/hrHPV-positive cases by MRT. CIN2+ lesions were detected in 108 of 142 (76.1%) HPV16-positive and/or HPV18-positive women by the PCR the HPV test. Among 128 hrHPV-negative ASC-H cases by both methods, CIN2+ lesions were identified in 21 of 128 (16.4%), including five cervical carcinomas (3.9%). The sensitivity, specificity, positive predictive value, and negative predictive value for patients in the composite group with HPV16/52/58/33/31 were 88.0%, 40.8%, 62.7%, and 75.0%, respectively. CONCLUSIONS: Papanicolaou tests classified as ASC-H are associated with a high CIN2+ rate and warrant colposcopy, regardless of HPV status. The extent to which the risk-stratification provided by comprehensive HPV genotyping can inform the management of ASC-H cytology remains to be explored.

A case of fine-needle aspiration of a neck mass with atypical squamous cells and macrophages.

Head and neck lesions often undergo fine-needle aspiration to determine the appropriate management and therapeutic decisions. However, there are numerous diagnostic challenges encountered with these specimens, particularly, if atypical squamous cells are identified. Here, we present a case of an enlarging right neck mass in a 38-year-old female and discuss the diagnostic difficulties and potential pitfalls. Additionally, we review the approach to diagnosis, including differential diagnostic considerations as well as available ancillary testing.

Atypical squamous cells in urine cytology are associated with a significant risk of high-grade malignancy.

BACKGROUND: Atypical squamous cells (ASC) in urine cytology are rarely found, and their clinical significance is not well studied. Previous studies were limited by a small number of cases and a lack of objective grading of ASC and/or their correlation with accompanying urothelial cell abnormality (UCA). METHODS: The institutional database was searched over 10 years for urine cytology reports containing ASC or from patients who had a concurrent diagnoses of high-grade (HG) urothelial carcinoma with squamous differentiation or squamous carcinoma. ASC were defined as keratinized squamous cells and were subcategorized as reactive, koilocytosis, low-grade (LG) atypia, and HG atypia. Correlations with age, sex, specimen type, accompanying UCA, number of ASC, and the risk of HG malignancy (ROHM) were assessed. RESULTS: ASC were present in 0.15% of all urine specimens (123 of 81,018). Slides and clinical follow-up were available on 91 patients (median age, 71 years). LG and HG squamous atypia had ROHMs of 70% and 92%, respectively. ASC not accompanied and accompanied by UCA had ROHMs of 37% and 94%, respectively. Most malignancies (34 of 67; 51%) showed rare ASC in urine. Reactive changes and koilocytosis had 0% ROHM. CONCLUSIONS: ASC in urine cytology is a significant finding and is associated with a high ROHM. In the absence of accompanying UCA, LG squamous atypia had a lower ROHM than HG atypia. In the presence of UCA, LG and HG squamous atypia had ROHMs of over 90%. These findings suggest that ASC and their grade of atypia should be noted in the cytology report, and clinicians should be made aware of their clinical significance.

Atypical squamous cells of undetermined significance cervical cytology in Bahrain: Reporting rates, high-risk HPV testing, and cytologic and histopathologic follow-up findings.

Objective: Atypical squamous cells of undetermined significance cytology (ASC-US) is a challenging and equivocal diagnosis for pathologists in cervical Pap smears. The data on ASC-US cervical cytology in Bahrain are deficient. This study reviewed and identified the reporting rates, high-risk human papillomavirus (HPV) testing results, histopathologic follow-up findings, and the cytologic progression of patients diagnosed with ASC-US in Bahrain. Material and Methods: A retrospective chart review was conducted on the medical records of 23,888 women who had Pap smear test results between January 2019 and March 2022 at the main referral tertiary hospital in Bahrain to identify the ASC-US cases. High-risk HPV (hrHPV) genotype was identified, and the histopathological results of the cervical biopsy was recorded. In addition, cytologic follow-up Pap smear tests conducted within 1 year of ASC-US diagnosis were tracked to monitor the progression or regression of ASC-US. Results: In this study, 259 out of 23,888 women reported to have ASC-UC cytology results with a reporting rate of 1.1%. The mean age of the ASC-US cases was 43 ± 11.6. Thirty percent of the ASC-US cases tested positive for hrHPV, and they were predominantly infected with the other hrHPV genotype (75%). When the histopathological changes of the cervix were analyzed, 82.1% had normal histopathologic findings. However, low-grade cervical intraepithelial neoplasia-1 was reported in 2 cases (7.1%), and high-grade cervical lesions (cervical intraepithelial neoplasia-2 and higher) were reported in 3 cases (10.7%). Regarding the cytologic follow-up, most of the ASC-US cases were negative for intraepithelial lesion or malignancy (NILM) (73.8%) or had persistent ASC-US (17.9%). The remaining minority of cases progressed into either low-grade squamous intraepithelial lesions (6%) or high-grade squamous intraepithelial lesions (2.4%). There was a statistically significant and relatively strong association between the cytology follow-up findings and the hrHPV test results (χ2 [2] = 8.869, P < 0.012, Cramer's V = 0.417). Conclusion: This is the first and largest study to characterize the ASC-US cytology cases in Bahrain. The reporting rates of ASC-US fell within the worldwide reported range. Although most of the ASC-US cases regressed into NILM, ASC-US showed progression into more advanced cervical cytologic diagnoses or contributed to the malignant transformation of cervical tissue, especially in the presence of hrHPV infection which was positive in 30% of the ASC-US cases. This emphasizes the role of cotesting (combination of hrHPV genotyping and Pap smear test) and the importance of colposcopic evaluation of those women with cytologic follow-up tests at 1 year of diagnosis. Implementing these recommendations in the cervical cancer screening practice in Bahrain will help in having a better management plan for women diagnosed with ASC-US cervical cytology.

A case of lung FNA with atypical squamous cells.

Fine-needle aspiration (FNA) is a commonly employed method for initial diagnosis and work-up of pulmonary nodules. Utilization of rapid on-site evaluation (ROSE) has the added benefit of allowing for triaging of material as appropriate for ancillary studies including microbiology testing. While many pulmonary lesions are easily categorized by cytologic evaluation, more difficult cases exist. In particular, pulmonary lesions demonstrating atypical squamoid cells can cause diagnostic challenge given the morphologic overlap between benign and malignant pulmonary lesions showing atypical squamoid cells. We herein review these common and uncommon squamoid lesions, which may enter within the differential when encountering atypical squamoid cells in pulmonary FNA specimens with emphasis on morphologic pitfalls and approaches to appropriate categorization.

Successful Preventive Treatment of Oncogenic Transforming HPV Infections in Low-Grade Cytology (ASC-US/LSIL) Patients with an Adsorptive and Antioxidant Vaginal Gel.

OBJECTIVE: This study aimed to investigate the preventive effect of a vaginal gel on p16/Ki-67-positive abnormal cytological cervical findings (ASC-US, LSIL) and hr-HPV in women. METHODS: The study included 134 women with p16/Ki-67-positive ASC-US or LSIL. Participants were selected from a randomized controlled trial that focused on women with histological diagnoses of p16-positive CIN1 lesions or CIN2. In the treatment group (TG), 57 patients applied the vaginal gel daily for three months, while 77 patients in the "watchful wait" control group (CG) received no treatment. The study's endpoints were cytological development, p16/Ki-67 and hr-HPV clearances. RESULTS: At three months, cytopathological results improved in 74% (42/57) of patients in the TG, compared with 18% (14/77) in the CG. Progression occurred in 7% (4/57) of TG patients compared with 18% (14/77) of CG patients. The p16/Ki-67 status changed statistically significantly in favor of the TG (p < 0.001), with 83% (47/57) becoming negative, compared with 18% (14/77) in the CG. The prevalence of hr-HPV decreased significantly in the TG by 51%, and by 9% in the CG (p < 0.001). CONCLUSIONS: Topical application of the gel resulted in statistically significant clearance of hr-HPV and p16/Ki-67 concomitant with amelioration of cytological findings, thus providing effective prevention and protection against oncogenic development. TRIAL REGISTRATION: ISRCTN11009040, on 10 December 2019.

Analysis of the related factors of atypical squamous cells of undetermined significance (ASC-US) in cervical cytology of post-menopausal women.

Introduction: Atrophy of the reproductive tract mucosa caused by the decrease of estrogen may increase the detection rate of ASC-US in cervical cytology of post-menopausal women. In addition, other pathogenic infections and inflammation can change the cellular morphology and increase the detection rate of ASC-US. However, further studies are needed to elucidate whether the high detection rate of ASC-US in post-menopausal women leads to the high referral rate of colposcopy. Methods: This retrospective study was conducted to document ASC-US in cervical cytology reports at the Department of Cytology at Gynecology and Obstetrics, Tianjin Medical University General Hospital between January 2006 and February 2021. We then analyzed 2,462 reports of women with ASC-US at the Cervical Lesions Department. A total of 499 patients with ASC-US and 151 cytology with NILM participants underwent vaginal microecology tests. Results: The average reporting rate of ASC-US in cytology was 5.7%. The detection rate of ASC-US in women aged > 50 years (7.0%) was significantly higher than that in women aged ≤50 years (5.0%) (P<0.05). The CIN2+ detection rate was significantly lower in the post- (12.6%) than in pre-menopausal (20.5%) patients with ASC-US (P <0.05). The prevalence of abnormal reporting rate of vaginal microecology was significantly lower in the pre-menopausal group (56.2%) than that in the post-menopausal group (82.9%) (P<0.05). The prevalence of bacterial vaginosis (BV) (19.60%) was relatively high in the pre-menopausal group, but the abundance of bacteria-inhibiting flora (40.79%) was mainly an abnormality in the post-menopausal group. The vaginal microecological abnormality rate of the women with HR-HPV (-) of ASC-US was 66.22%, which was significantly higher than that of the HR-HPV (-) and the NILM group (52.32%; P<0.05). Discussion: The detection rate of ASC-US in women aged > 50 years was higher than that ≤50 years, but the detection rate of CIN2+ was lower in the post-menopausal women with ASC-US. However, vaginal microecological abnormalities may increase the false-positive diagnosis rate of ASC-US. The vaginal microecological abnormalities of the menopausal women with ASC-US are mainly attributed to infectious diseases such as BV, and it mainly occurs in the post-menopausal women was bacteria-inhibiting flora. Therefore, to avoid the high referral rate for colposcopy, more attention should be paid to the detection of vaginal microecology.

A Practical Approach to Squamous Abnormalities on Cervical Cytology: Overview of Interpretive Criteria and Guidance for Altering Thresholds in Response to Quality Assurance Findings.

BACKGROUND: Squamous intraepithelial lesions observed in Papanicolaou (Pap) test gynecologic cytology arise as a result of infection of the cervicovaginal tract by human papillomavirus (HPV). The viral cytopathic effect of HPV manifests as koilocytosis, also known as low-grade squamous intraepithelial lesion (LSIL) in The Bethesda System (TBS). Integration of HPV genetic material into the genome of squamous cells can, in some women, result in progressive accumulation of mutations and abnormalities of growth and maturation leading to high-grade squamous intraepithelial lesion (HSIL) and possibly invasive squamous cell carcinoma. Due to morphologic overlap between reactive processes and these changes related to HPV, TBS includes equivocal categories that may be applied to Pap tests with uncertain morphology: atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells cannot exclude HSIL (ASC-H). Quality assurance (QA) measures in gynecologic cytology laboratories aim to maximize the sensitivity for LSIL and HSIL lesions while simultaneously keeping the use of ASC-US at reasonable levels. SUMMARY: TBS provides a comprehensive nomenclature for squamous abnormalities encountered in screening, but subjectivity in interpretation remains. QA practices attempt to identify problematic patterns of misinterpretation for correction. KEY MESSAGE: This review aimed to provide practical recommendations for cytology practitioners seeking to alter their interpretive thresholds for ASC-US, LSIL, and HSIL in response to feedback from QA procedures indicating deviation from desired norms.

Establishment and validation of a risk prediction model for high-grade cervical lesions.

OBJECTIVE: To establish and validate a risk prediction model for cervical high-grade squamous intraepithelial lesions (HSIL). METHODS: This retrospective study included patients who underwent cervical biopsies at the Cervical Disease Centre of Maternal and Child Hospital of Hubei Province between January 2021 and December 2021. RESULTS: A total of 1630 patients were divided into the HSIL + cervical lesion group (n = 186) and the ≤ LSIL cervical lesions group (n = 1444). LSIL, ASC-H, HSIL and SCC, high-risk HPV, HPV16, HPV18/45, multiple HPV strains, acetowhite epithelium, atypical vessels, and mosaicity were independently associated with HSIL + lesions. These factors were used to establish a risk prediction model with a demonstrated area under the curve (AUC) of 0.851 and a C-index of 0.829. Calibration curve analysis showed that the model performed well, with a mean absolute error (MAE) of 0.005. The decision curve showed that the model created by combining the risk factors was more specific and sensitive than each predictive variable. CONCLUSION: The model for predicting HSIL demonstrated promising predictive capability and might help identify patients requiring biopsy and treatment.

Cervical Epithelial Abnormalities and Associated Factors among HIV-Infected Women in Lagos, Nigeria: A Cytology-Based Study.

INTRODUCTION: As it may not be feasible to provide cervical cancer screening services to all HIV-infected women in most resource-limited settings, there is a need to identify those who are most at risk. We determined the prevalence, patterns, and associated factors of cervical cytological abnormalities among HIV-infected women in Lagos, Nigeria. METHODS: This descriptive cross-sectional study was conducted among HIV-infected women at the adult HIV treatment and colposcopy clinics of a university teaching hospital in Lagos, Nigeria, between October 2018 and December 2019. A cervical sample was collected from each woman to detect cervical cytological abnormalities. RESULTS: Of the 593 enrolled women, cervical cytological abnormalities were present in 40 (6.7%). Most (37.5%) of the women with cytological abnormalities had atypical squamous cells of undetermined significance. Age at coitarche (<20 vs. ≥20 years: adjusted odds ratio, 2.42; 95% confidence interval, 1.21-4.83, p = 0.01) was the only factor that was independently associated with cervical epithelial abnormalities. CONCLUSION: The prevalence of cervical cytological abnormalities in our study is lower than most previous reports in Africa. Sexual debut at an early age was significantly associated with cytological abnormalities. It is necessary to confirm the findings of this study through a well-designed and adequately powered longitudinal study.

Primary screening of cervical cancer by Pap smear in women of reproductive age group.

Introduction: Cancer cervix is a major health problem responsible for causing a higher mortality rate in women worldwide; the exponential increase in such cases can be reduced by early screening of women. The cytology-based cervical screening had a higher success rate in reducing the incidence of cervical cancer. The present study aimed to evaluate the use of Pap smear screening to find cytological abnormalities and precancerous lesions. Materials and Methods: Sexually active women over 21 years of age were enrolled for the study. A detailed history was taken on the preformed proforma, and all were subjected to vaginal examination. Samples for Pap smear were taken with the help of Ayre spatula and immediately spread over a marked grease-free glass slide and dipped into 95% ethyl alcohol fixative for cytological examination. Results: Most of the abnormality of the epithelial cells found was in the age range of 31-50 years, and most of them were multiparous. 47.92% of the women had a chief complaint of vaginal discharge, an irregular menstrual cycle in 11.07%, and abdominal pain in 7.83%, while 30.41% were asymptomatic. Women found negative for intraepithelial neoplasia were 82.94%, while 13.36% had an inflammatory smear. 0.92% atypical squamous cells of undetermined significance (ASCUS), 2.78% Low-grade squamous intraepithelial lesion (LSIL) were found, no woman had High-grade squamous intraepithelial lesion (HSIL). Conclusion: Pap smear is a simple, cost-effective, non-invasive, and easy to perform tool for early detection of precancerous lesions, and it is evident that every woman above the age of 25-30 years must be recommended for cervical screening.

Condyloma acuminatum of the urinary tract demonstrates atypical squamous cells in urine cytology.

Urine cytology of urinary tract condylomas has not been systematically studied. We analyzed cytologic features of urinary tract condylomas and evaluated potential diagnostic challenges and pitfalls. We retrospectively reviewed urine cytology of urinary tract condylomas from 2 academic institutions (2015-2022). Among 20 patients with urinary tract condylomas, 6 had urine cytology (2 samples in 1 patient), including 3 men and 3 women (mean age, 74.3 years; range, 65-86 years). Original interpretations were negative for high-grade urothelial carcinoma (NHGUC; n = 4), atypical urothelial cells (n = 1), reactive urothelial cells (n = 1), and negative for malignancy (n = 1). Squamous cells were noted in 3 cases, atypical squamous cells (ASC) consistent with low-grade squamous intraepithelial lesion (LSIL) were noted in 1 case, and in 3 cases, the presence of squamous cells was not mentioned. All urines were reclassified according to The Paris System as NHGUC. Specimens were composed of benign urothelial cells and groups or isolated ASC consistent with LSIL (n = 4), atypical keratinized squamous cells (n = 2), and ASC that did not meet LSIL criteria (n = 1). The LSIL cells showed nuclear enlargement (n = 4), hyperchromasia (n = 4), perinuclear halo (n = 3), nuclear membrane irregularity (n = 4), orangeophilic cytoplasm (n = 3), and binucleation (n = 4). The atypical keratinized squamous cells showed hyperchromasia (n = 2), nuclear membrane irregularity (n = 2), keratin pearls (n = 2), and binucleation (n = 1). The ASC that did not meet LSIL criteria showed nuclear enlargement and orangeophilic cytoplasm. Many urinary tract condylomas (57%) demonstrate classic LSIL features in urine cytology. Less frequent cases can mimic keratinizing squamous cell carcinoma (28%) or demonstrate ASC not diagnostic of LSIL (15%).

ThinPrep cytologic test combined with HPV typing to evaluate the degree of cervical diseases and the relationship between HPV typing and the pathological results of patients with atypical squamous cells of undetermined significance: a diagnostic test.

Background: Persistent infection with high-risk human papilloma virus (HPV) is the main cause of cervical cancer. Cervical precancerous lesions last for long and are reversible. Thus, the effective way to prevent cervical cancer is to make a timely diagnosis and administer treatment in the precancerous stage. This study sought to explore the evaluation of cervical cytology by a ThinPrep cytologic test (TCT) combined with HPV typing in patients with cervical diseases, and the relationship between HPV typing and the pathological results of patients with atypical squamous cells of undetermined significance (ASCUS). Methods: The medical records of 414 patients who received outpatient treatment at the Suzhou Hospital of Traditional Chinese Medicine from February 2020 to February 2022. The pathological results of all cases were followed-up, and data on patients' age, menopause, pregnancy status, birth status, HPV typing, and HPV infection status were collected and statistically analyzed. The positive predictive value, negative predictive value, sensitivity, and specificity of the 2 detection methods were calculated. The factors associated with ASCUS pathological results were analyzed by logistic regression. Results: Among the 414 patients, 230 had positive vaginal tissue biopsy results, taking this as the gold standard, the diagnostic value of TCT and HPV were examined and compared. HPV typing had a slightly higher sensitivity and positive predictive value than TCT; however, the 2 methods combined had the highest sensitivity and positive predictive value. The univariate analysis showed that the age, HPV infection, and HPV typing in the group of chronic cervicitis differed significantly from the group of cervical intraepithelial neoplasia (CIN) II+/cervical carcinoma (P<0.05). The logistic regression analysis showed that HPV infection, being HPV-16 positive, and being HPV-18 positive were risk factors of ASCUS disease (P<0.05). Conclusions: Compared to individual detection methods, TCT combined with HPV typing had a higher detection rate and screening accuracy for cervical diseases, and had the highest sensitivity and positive predictive value. HPV infection, being HPV-16 positive, and being HPV-18 positive are risk factors for ASCUS lesions. HPV typing detection can improve the accuracy of ASCUS shunt diagnosis and provide a reliable basis for the establishment of ASCUS shunt management.

Evaluation of P16/Ki67 (CINtecPlus) and L1-capsid compared with HPV-genotyping in cervical cytology in women ≥35 years old focusing on patients with atypical squamous cells of undetermined significance.

Cervical cancer is the third most common cancer in women worldwide. Conventional cytological examination as a screening method with Papanicolaou has been established to reduce the incidence of dysplasia and cervical cancer for years. In addition to the conventional screening, the introduction of immunocytochemical examinations, including CINtecPlus and L1-capsid, has been demonstrated to have a positive impact on screening results. In addition to morphological screening methods, human papillomavirus (HPV)-testing has also been demonstrated to possess an enormous potential in the cervical screening process. Additionally, different screening models ranging from conventional cytological screening to primary HPV-testing do exist in different countries. At the beginning of the year 2020, a combination of cytological screening and HPV-testing was introduced in Germany for women ≥35 years. The aim of the present study was to evaluate the role of morphological screening, including immunocytochemistry, and to compare it with HPV-genotyping. Immunocytochemistry was added to confirm the diagnosis but needs established infrastructure and well-trained personnel. Furthermore, there was a need to establish the HPV-screening method. In the Institute for Pathology and Cytology (Schuettorf, Leer, Germany), 146,800 samples of women (>35 years old) were examined between January 2020 and January 2021. The present study retrospectively analyzed 146,800 samples. Each sample was examined using a conventional cytological technique and HPV-high risk-Test (HPV-HR-Test) with Viper-BD. Immunocytochemistry with CINtecPlus and L1-capsid was added in some cases. A total of 555 cases were cytological diagnosed as atypical squamous cells of undetermined significance (ASC-US; IIp). After performing immunocytochemistry, 79% of cases were suspected to be positive and 1.48% of cases were definitely positive. The HPV-HR-Test was positive in 26.4% of cases. Among cases of ASC-US and HPV-HR-negativity, 33.7% were suspicious of immunocytochemical positivity and 0.5% were definitely positive. Among patients with HPV-16-negativity, 13.6% were patients with highly squamous intraepithelial lesion (HSIL) and 22.7% were patients with low-grade squamous intraepithelial lesion (LSIL) and HSIL. Among patients with HPV-18-negativity, 14.3% were patients with HSIL and 19.5% were patients with LSIL and HSIL. There were 107 cases in this group of cases with negativity of both HPV-16 and HPV-18. After performing the colposcopy and biopsy, there were 6.5% with cervical intra-epithelial neoplasia (CIN) I, 8.4% with CIN II and 5.6% with CIN III. In conclusion, there is still a need for conventional cytological examination and maybe the addition of immunocytochemistry to confirm the diagnosis and to exclude dysplasia of cervical epithelium. The HPV-HR-Test is not enough as a screening method and may be misleading.

The gray zone squamous lesions: ASC-US / ASC-H.

The unequivocal and easily recognizable entities of LSIL and HSIL pose no diagnostic problems for a trained eye. However, when the defining morphologic features are either qualitatively or quantitatively insufficient, it is then that the borderline category of "Atypical Squamous cells" (ASC) may have to be used. Scant and suboptimal preparations (mainly in conventional smears) are the common causes that hinder confident decision-making. The binary classification of the ASC category has been retained in The Bethesda System 2014. It includes ASC of undetermined significance (ASC-US) when the atypia is seen in mature cells and ASC-cannot rule out high-grade lesion (ASC-H) when borderline changes are seen in less mature, smaller metaplastic cells or smaller basaloid cells. There are many criticisms of the ASC category. The major one is its subjective and inconsistent applications and the low interobserver and intraobserver reproducibility. However, studies have shown that if we eliminate ASC-US, the LSIL rate will increase. If ASC-H is eliminated, the chances of detecting true lesions are reduced. Hence, there are strong reasons to retain the ASC category. The usual problems leading to the categorization of such cells as atypical are hyperchromasia beyond that acceptable as reactive change; abnormal chromatin pattern that is not overt dyskaryosis; minor variations in nuclear shape; and membrane outlines. Qualifying the atypical cells precisely in one of the categories has bearing on the clinical management and follow-up of the patient. Surveillance of women under the ASC-US category is either by repeat smear at 6 months and 1 year or by reflex human papillomaviruses DNA testing. Women with a Pap smear interpretation of ASC-H are directed to undergo immediate colposcopy. This article describes in detail the morphologic features of the ASC category, doubts about the correct interpretation of the chromatin pattern of the cells in question, and the differential diagnosis between normal, reactive, or inflammatory conditions, and LSIL/HSIL.

Scrutinizing high-risk patients from ASC-US cytology via a deep learning model.

BACKGROUND: Atypical squamous cells of undetermined significance (ASC-US) is the most frequent but ambiguous abnormal Papanicolaou (Pap) interpretation and is generally triaged by high-risk human papillomavirus (hrHPV) testing before colposcopy. This study aimed to evaluate the performance of an artificial intelligence (AI)-based triage system to predict ASC-US cytology for cervical intraepithelial neoplasia 2+ lesions (CIN2+). METHODS: More than 60,000 images were used to train this proposed deep learning-based ASC-US triage system, where both cell-level and slide-level information were extracted. In total, 1967 consecutive ASC-US Paps from 2017 to 2019 were included in this study. Histological follow-ups were retrieved to compare the triage performance between the AI system and hrHPV in 622 patients with simultaneous hrHPV testing. RESULTS: In the triage of women with ASC-US cytology for CIN2+, our system attained equivalent sensitivity (92.9%; 95% confidence interval [CI], 75.0%-98.8%) and higher specificity (49.7%; 95% CI, 45.6%-53.8%) than hrHPV testing (sensitivity: 89.3%; 95% CI, 70.6%-97.2%; specificity: 34.3%; 95% CI, 30.6%-38.3%) without requiring additional patient examination or testing. Additionally, the independence of this system from hrHPV testing (κ = 0.138) indicated that these 2 different methods could be used to triage ASC-US as an alternative way. CONCLUSION: This de novo deep learning-based system can triage ASC-US cytology for CIN2+ with a performance superior to hrHPV testing and without incurring additional expenses.

Targeted Next Generation Sequencing for Human Papillomavirus Genotyping in Cervical Liquid-Based Cytology Samples.

At present, human papillomavirus (HPV) testing is replacing morphology-based cytology as the primary tool for cervical cancer screening in several countries. However, the HPV assays approved for screening lack detection for all but one of the possibly carcinogenic HPV types and do not genotype all included HPV types. This study demonstrates the use of a targeted HPV next generation sequencing (NGS) panel to detect and genotype all 25 carcinogenic, probably carcinogenic, and possibly carcinogenic HPV types as well as the low-risk types HPV6 and HPV11. The panel was validated using a cohort of 93 paired liquid-based cytology samples (general practitioner (GP)-collected cervical samples and cervico-vaginal self-samples (SS)). Overall, the targeted panel had a sensitivity (GP = 97.7%, SS = 92.1%) and specificity (GP = 98.0%, SS = 96.4%) similar to the commercial HPV assays, Cobas® 4800 HPV DNA test (Roche) and CLART® HPV4S assay (GENOMICA). Interestingly, of the samples that tested positive with the NGS panel, three (6.4%) of the GP-collected samples and four (9.1%) of the self-samples tested positive exclusively for HPV types only included in the NGS panel. Thus, targeted HPV sequencing has great potential to improve the HPV screening programs since, as shown here, it can identify additional HPV positive cases, cases with HPV integration, variants in the HPV genome, and which HPV type is dominant in multi-infected cases.

Liquid-Based Cytology in the Detection of Premalignant Lesions in Patients with "Atypia in Squamous Cells" in Conventional Cytology.

Background: The management of patients with "Atypical Squamous Cells" (ASC) in conventional papanicolaou smears (CPS) is based on the risk of high-grade squamous intraepithelial lesion (HSIL). The efficacy of liquid-based cytology (LBC) to detect this premalignant lesion is variable, with little evidence of its performance in Colombian patients. Aims: The aim of this study is to determine the performance of LBC in the detection of premalignant lesions, in patients with ASC in CPS. Materials and Methods: Were obtained patients who attended colposcopy clinic due the result of ASC in CPS. An LBC was taken, which was interpreted by two pathologists without access to other results. The performance of LBC to detect HSIL, was determined, considering as a gold standard: histopathological study/negative-satisfactory colposcopy. Results: Were included 114 patients, with a mean age of 38.4 years (SD ± 13.3). LBC had abnormal results in 40.36% (n = 46), with a slightly higher proportion of low-grade squamous intraepithelial lesion (LSIL) than HSIL. The total of abnormal diagnoses by colposcopy and/or biopsy was 51.75% (n = 59), with a predominance of LSIL (36.84%). The sensitivity of the liquid-based cytology to detect premalignant lesions was 76.5%, specificity: 66.0%, positive predictive value: 28.3% and negative predictive value: 94.1%; The Cohen's kappa index of LBC for detecting HSIL was 0.2492 for the total population and 0.2907 for ≥30 years. Discussion: Although LBC decreases abnormal cytology and increases the detection of HSIL, which improves diagnostic accuracy; sensitivity and predictive values for detecting HSIL are not significantly different between CPS and LBC.

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.