Cervicovaginal Cytology Research Articles

Decreased HPV Detection in Unsatisfactory Cervicovaginal Cytology: Quality and Safety Implications for Primary HPV Screening?

Decreased HPV Detection in Unsatisfactory Cervicovaginal Cytology: Quality and Safety Implications for Primary HPV Screening?

Help and learn with gynecological cytology

Literary references concerning conventional cervicovaginal cytology are increasingly scarce. Cytological screening as a weapon to fight cervical cancer has been a success in those countries where it has been implemented, especially if it has been universal. Unfortunately, globally, this circumstance is not possible, mainly due to socioeconomic reasons. This means that cervical cancer continues to be a major cause of death worldwide.

Tiempos y condiciones de almacenamiento de las muestras en anatomía patológica. Recomendaciones de la Sociedad Española de Anatomía Patológica parte 1: muestras destinadas al diagnóstico

IntroductionThe correct storage of specimens in the Pathology service is of vital importance for patient safety. However, there are no clear recommendations as regarding how long samples should be stored for a minimum period. Material and methodsA working group of the Spanish Society of Anatomic Pathology has reviewed a series of recommendations established in the literature and after two rounds of consultations and a discussion and voting phase has established a series of storage time proposals. ResultsEach of the proposals is presented with the data found in the literature and sometimes offers definitions and exceptions to the proposal. ConclusionThese recommendations, which are minimums, establish a period of at least 10 years for paraffin embedded blocks (including cell blocks), histological preparations, general cytology, pathologic cervico-vaginal cytology and electron microscopy blocks; at least 3 years for cervico-vaginal cytology, 5 years for extracted nucleic acids, at least 4 weeks for tissue in formalin and from the time of diagnosis for liquid cytology material and fluids.

Analysis of the Differences between Bethesda Groups according to Conventional Smear and Liquid-Based Cytology Methods in Cervicovaginal Cytology: A Single-Center Experience with 165,915 Cases

Introduction: Liquid-based cytology (LBC) has replaced conventional smear (CS) in the world. In this study, through a series with a large number of cases, we aimed to make a comparison and general evaluation in all groups, primarily epithelial abnormalities, according to LBC and CS methods. This study was carried out in a private pathology laboratory located in a metropolitan city, where cytological materials sent from many clinics were examined. Material and Methods: There were 165,915 cases whose smears were examined between 2012 and 2020, most of them conventional (131,224 CS, 34,691 LBC). Cases were evaluated on the basis of the Bethesda 2014 classification and divided into sub-diagnostic categories after they were divided into two main groups as “with epithelial abnormalities” and “without.” χ2 and Fischer’s precision statistical tests were conducted using SPSS 23.0 package. In the CS process, cervical samples were obtained using an endocervical brush and a spatula. Cells were directly spread onto the slides and promptly fixed in 95% ethanol, followed by staining with the standard Papanicolaou stain. For LBC ThinPrep, cervical specimens were gathered using a cervix brush. The brush was washed in a vial and discarded. Finally, cells were isolated through vacuum filtration and transferred to the slide using air pressure. Results: Squamous cell abnormalities (atypical squamous cells of undetermined significance [ASC-US], atypical squamous cells – cannot exclude high-grade squamous intraepithelial lesion [ASC-H], low-grade squamous intraepithelial lesion [LSIL], high-grade squamous intraepithelial lesion [HSIL], squamous cell carcinoma, atypical glandular cells of undetermined significance) were reported in 5,696 (3.43%) cases. ASC (ASC-US + ASC-H)/SIL ratio (1.36/2.04) was found to be 0.67 (recommended Bethesda ratio is <3). ASC-US (p < 0.001), ASC-H (p < 0.001), and HSIL(p < 0.001) detection rate of LBC was found to be significantly higher than CS. ASC-US (1.8/1.2), ASC-H (0.08/0.008), and HSIL (0.6/0.3) case ratios of LBC/CS were found to be significantly higher in LBC. LSIL (1.72/1.66) rate was similar. Conclusion: LBC is superior to CS in detecting epithelial lesions. In addition to being used as a screening method, it is clear that it makes a great contribution to reducing cervical carcinomas due to HPV typing. Definitive comments regarding comparison of methods on reactive changes and microorganism detection are challenging. Preanalytical factors might account for these situations.

Validation of full-remote reporting for cervicovaginal cytology: the Caltagirone-Acireale distributed lab.

Cervical cancer is the fourth most common cancer in women, and its prevention is based on vaccination and screening. Screening consists of molecular human papillomavirus (HPV) testing and cytologic analysis of cervical smears, which require expensive equipment and the interaction of numerous professionals such as biologists, cytologists, laboratory technicians, and pathologists. We centralize the cervical samples from more than 51 clinics in 1 main laboratory, where automated HPV testing is performed. HPV-positive cases are collected and used to prepare a liquid-based cytology slide, which is stained and immediately scanned. The resulting whole-slide images (WSIs) are immediately available in a remote laboratory where they are examined by experienced cytologists using virtual microscopy. This setup was validated by making each of the 3 readers independently diagnose 506 specimens in random order, using both conventional light microscopy (CLM) and WSIs, with a minimum wash-out period of 3 weeks and with a final discussion for all cases. Intraobserver agreement among CLM and WSI ranged from 0.71 to 0.79, and interobserver agreement for the 3 readers compared with the consensus diagnosis was similar for the 2 modes of assessment. Readers subjectively felt confident in their WSI diagnosis for inadequate and negative cases, but less so in other cases. The perceived difficulty was slightly higher in WSI readings. Interobserver agreement in cervicovaginal cytology is moderate and does not vary if the slides are examined conventionally or digitally. Despite higher reported subjective difficulty and lower confidence in the WSI diagnosis, we did not observe a deterioration in diagnostic performance using WSI compared with CLM.

Comparison of glass and digital slides for cervical cytopathology screening and interpretation.

Cervical cancer is the second most common form of cancer and a leading cause of premature death among women aged 15 to 44 worldwide. In Brazil, there is a high prevalence of infection by the human papillomavirus - HPV. Digital pathology optimizes time and space for reading cervicovaginal cytology slides. We evaluated the feasibility of using whole slide images (WSI) for the routine interpretation of cytology exams. A total of 99 cases of vaginal cytology were selected from a reference laboratory in Northeastern Brazil. Three cytotechnicians participated in the study. Cellular atypia was the one that most presented concordance values. Two observers almost perfectly agreed (k = 0.86 and k = 0.84, respectively) on the negative diagnoses. The performance of the evaluators for NILM (negative for intraepithelial lesion and malignancy) showed high reproducibility and sensitivity in the digital slides, mainly between evaluators A and C. In contrast, the microbiology group showed disagreement between the diagnoses by digital slides and the standard- gold. The concordance between the digital diagnoses and the gold standard for ASCUS was 89%. In the inflammatory category, Spearman's test showed similar results between raters A, B, and C (rs = 0.47, rs = 0.41, and rs = 0.47, respectively). This study reports the diagnostic validation using digital slides in view of the need to optimize the cytology visualization process. Our experience shows good diagnostic agreement between digital and optical microscopy in several analyzed categories, but mainly in relation to cellular atypia and inflammatory processes.

Cervicovaginal Papanicolaou tests in transgender men: Cytomorphologic alterations, interpretation considerations, and clinical implications.

The transgender population faces unique psychosocial and physical obstacles to cervical cancer screening. Additionally, most individuals undergo masculinizing testosterone hormone therapy, and the physiologic changes can cause cytomorphologic alterations that may mimic lesions. Although the literatureon cervicovaginal cytology is growing in this patient population, it is still limited. The pathology information system was queried for all Papanicolaou (Pap) tests from transgender men from January 2013 to February 2023. The original diagnostic categories were catalogued. Cases were reviewed to evaluate the cytomorphologic alterations. Clinical data were also sought, including whether the sample was self-collected. Two comparison groups were established: one was a postpartum atrophic group and the other was an all-comer group. A total of 51 cases from 43 individuals were identified, with a mean age of 31 years. Approximately a third of cases (18 of 51; 35%) were self-collected. The abnormal rate was low, with 5.9% of cases rendered atypical squamous cells of undetermined significance on original review and no lesions identified. The Pap unsatisfactory rate according to original reports was 3.9%. This increased to 13.7% when the cases were rereviewed, which was significantly higher than the all-comer comparison group. The unsatisfactory rate did not correlate with self-collection. Atrophy was a prevalent cytomorphologic alteration, with the vast majority of cases (92%) showing at least mild atrophy. Small blue cells and transitional cell metaplasia were seen in many cases (53% and 43%, respectively). There are clinical and morphologic considerations that are distinct to the transgender patient population. Laboratory personnel and diagnosticians need to be aware of these in order to optimize patient care.

Homage to Georgios Papanikolaou: A pilgrimage to his birthplace.

As a cancer epidemiologist focused on the science of cervical cancer prevention and control, the author journeyed to the home of his hero, Georgios Nikolaou Papanikolaou, whose pioneering contribution of the cervicovaginal cytology test (the Pap test) has saved countless female lives over generations throughout the world, laying the groundwork for one of the most beautiful stories in public health.

Updates in Cervical Cancer Screening Guidelines, The Bethesda System for Reporting Cervical Cytology, and Clinical Management Recommendations.

Over the past decades, cervical cancer has been a worldwide public health problem. Population-based early cancer risk detection and prevention approaches, including vaccination, cytology screening and human papilloma virus (HPV) detection, with the aligned clinical management, have formed a well-rounded high-quality implementation system for cervical cancer control, and revolutionarily improved the quality of life of women: (1) the success of cervical cancer screening practices, (2) standardization of The Bethesda system for reporting cervicovaginal cytology, (3) improvement in the understanding of HPV pathogenesis in cervical cancer, and (4) the development of appropriate management approaches have significantly decreased the disease burden of cervical cancer worldwide. This scoping review aimed to understand the evolvement of cervical cancer screening and management guidelines, describe the Bethesda cervical cytology reporting system, and HPV vaccines and tests, and highlight the key information of present policies and practices.

Conjugate treatment with high concentration normobaric oxygen and hyaluronic acid for vaginal atrophy: a prospective study.

Vulvovaginal atrophy is a condition closely related to low circulating estrogen levels, with post-menopause being the main cause. However, patients of childbearing age may also present with these symptoms due to treatments that reduce estrogen production. Local estrogen therapy is the causal treatment of local symptoms, but it is not always accepted and is often abandoned by patients. In recent years, alternative therapies have been proposed: fractional CO2 laser or the conjugate treatment with normobaric oxygen and hyaluronic acid, the latter being the subject of this study. The study aimed to evaluate the effectiveness of conjugate topical treatment with normobaric oxygen and hyaluronic acid. 50 patients were evaluated and treated with 5 applications of 15 minutes each, every 15 days, with Caressflow®. All patients presented at least one of the symptoms related to vulvovaginal atrophy: dryness, burning, and dyspareunia. In all cases, vulvoscopy, colposcopy, and cervicovaginal cytology were performed. The patients were interviewed with an analogic scale (VAS) concerning the severity of symptoms before and after the treatment. Colposcopy and PAP-smear were assessed by mean of Vaginal Health Index Score (VHI) at baseline and at the end of the treatment. All patients completed the treatment scheme and presented with a significant improvement in subjective symptoms. The colposcopy and PAP-smear performed 10 days after the end of the last treatment showed a significant improvement in the appearance and elasticity of the vaginal epithelium and the cytological picture, which showed, in the sample taken after treatment, hyaluronic acid vesicles within the cell cytoplasm. This study corroborates the data presented in the latest published papers on the effectiveness of treatment with normobaric O2 and hyaluronic acid on vaginal atrophy. Efficacy has been confirmed both in terms of subjective symptoms reported by the patients and objective improvement at colposcopy and PAP-smear cytology.

Villoglandular Adenocarcinoma of the Uterine Cervix: A Case Report.

Cervical adenocarcinomas constitute for approximately 10%-20% of all invasive cervical cancers. Villoglandular adenocarcinomas (VGAs) are a rare subtype of cervical adenocarcinoma, representing approximately 5% of all cases of cervical adenocarcinomas. Herein, we report the case of a 49-year-old perimenopausal woman successfully treated for VGA. The patient presented to the hospital with a primary complaint of vaginal discharge persisting for 7 months with worsening symptoms. She had no underlying medical conditions or history of oral contraceptive use. A punch biopsy revealed an adenocarcinoma, and a human papillomavirus (HPV) test indicated positive for HPV-16. The patient underwent a radical hysterectomy with bilateral pelvic lymph node dissection, and a pathological diagnosis of VGA was established. After surgery, the patient underwent a 6-week course of concurrent chemoradiotherapy with cisplatin. During the 42 months of follow-up, no signs of disease recurrence or metastasis were observed. Because of the limitations of specimen acquisition, achieving a precise diagnosis through cervicovaginal cytology and punch biopsy is challenging. Instead, conization should be considered to prevent misdiagnosis.

Effect of different contraceptive methods on cervico-vaginal cytology

Effect of different contraceptive methods on cervico-vaginal cytology

HPV-Negative High Grade Cervicovaginal Cytology: Corresponding Outcomes and Surgical Gynecology Findings

HPV-Negative High Grade Cervicovaginal Cytology: Corresponding Outcomes and Surgical Gynecology Findings

Never stop wondering: When cells become PAP-art on the slides.

The project named Victoria's cells was created to train health care personnel, especially in low-income countries. This innovative approach is designed to associate benign and malignant cellular images and/or patterns with a range of shapes and color shades to evoke animals, common objects, and colorful aquariums. The project makes use of familiar images to capture the viewer's interest as an aid for cytological interpretation. Cervicovaginal cytology is processed with conventional and liquid-based cytology. The images are visually compelling to highlight the importance of studying cells and their diagnostic significance. Infectious diseases as well as malignant cells are thereby easily recognized. The pictures are organized into different sections, including Victoria's zoo, Victoria's fantasy, and malignant mockery. Branching mycelia resemble a starfish; squamous metaplasia recalls a sea turtle's shell. Among others, different patterns of endometrial, endocervical, and squamous cells can resemble fish tanks populated by cells with the shapes of pufferfish, anglerfish, whales, scorpions, and garfish. The sea transitions to the earth, with a sly cat, a little elephant, a dog, and a koala. Other cellular preparations resemble a gymnast, a geisha, and a plunging diver as well as hummingbirds, a heron, a water lily, and a peony. The malignant mockery section is composed of squamous intraepithelial lesion patterns that resemble monsters, eyes, a foul tongue, eagles, and feathers. In conclusion, the recognition of visual images can make the study of cytology simpler and more enjoyable and serve the final objectives of prevention and cure.

High-risk human papillomavirus testing in cytology aspiration samples from the head and neck part 1: a review of the literature on available testing options.

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma is increasing in incidence and is often first diagnosed on a cytology fine needle aspiration (FNA) specimen of metastatic nodal disease of the neck. In the setting of oropharyngeal squamous cell carcinoma, HPV status defines the disease with HPV-associated tumors having better overall prognosis than those that are HPV negative. Furthermore, metastatic squamous cell carcinoma of the neck of unknown origin requires testing for HPV as a positive result suggests an oropharyngeal primary. As a result, HPV testing in aspirate samples is increasingly important for the proper diagnosis and treatment of patients with head and neck squamous cell carcinoma. Although HPV testing in cervicovaginal cytology specimens is common and well-established, testing in head and neck FNA samples remains challenging. p16 immunohistochemistry is an excellent surrogate marker for HPV in tumors of known or suspected oropharyngeal origin, but the criteria used in histologic specimens may not be appropriate in cytology samples. FNA samples are more frequently hypocellular, and cytology cell blocks have variable fixation and processing steps, limiting the utility of p16 immunohistochemistry. Other potential testing options have been reported in the literature including staining of aspirate smears and molecular testing of liquid-based samples. The American Society of Cytopathology Clinical Practice Committee recently surveyed the American Society of Cytopathology membership to determine the current state of HPV testing in aspirate samples, and this review article is designed to provide a summary of the current literature on various testing options in FNA samples.

Cellular debris on negative liquid-based cytology cervicovaginal smears.

To determine the prevalence of cellular debris (CD) on benign cervicovaginal liquid-based cytology (LBC) smears and which factors predict the presence and larger amount of CD. Cervicovaginal smears evaluated as negative for intraepithelial lesion or malignancy (NILM) between 1 January and 31 March 2020 were retrospectively reviewed to record the presence and amount of CD. All smears were prepared with the SurePath platform. Patient ages and past medical and surgical histories were also retrieved. Multivariate regression analyses were performed to find positive predictors of a larger amount of CD. Three hundred forty-nine NILM smears were included in this study. The cohort consisted of 222 cervical smears (CS), and 127 vaginal smears (VS) taken from patients who had undergone hysterectomy. Overall, CD was observed in 111 (31.8%) cases. The positive predictors of CD were increasing age, specimen type (VS compared to CS), history of chemotherapy or radiation therapy (CRT), and more than mild background inflammation. Among the VS group, CD was present in 64 cases (50.4%) regardless of the time between the hysterectomy and specimen collection. Positive predictors in the VS group were age and more than mild inflammation. By contrast, the prevalence of CD in the CS group was 21.2%, and age was the only positive predictor. Histories of CRT, conisation, and inflammation were not statistically significant positive predictors for CD among CS. Cellular debris could be seen in as much as 50% of NILM smears taken after hysterectomy, regardless of the time since the procedure. Increasing age was a positive predictor of the presence and a larger quantity of CD. These findings are helpful when evaluating smears with moderate to abundant debris in the background with questionable cellular atypia.

Cervicovaginal cytology, HPV testing and vaginal flora in transmasculine persons receiving testosterone.

Testosterone is one of the strategies that transmasculine persons can elect in order to align physical traits to their gender identity. Previous studies have shown morphologic changes in the genital tract associated with testosterone. Here, we aim to evaluate cervicovaginal cytology specimens (Pap tests) and high-risk HPV (HR-HPV) testing from transmasculine individuals receiving testosterone. This is a retrospective cohort of 61 transmasculine individuals receiving testosterone from 2013 to 2021. Cytologic diagnoses from 65 Pap tests were correlated with HPV status and histologic follow-up and compared with the institutional data and a cohort of cisgender women with atrophic changes. The median age was 28 years and median time of testosterone use was 3 years. Transmasculine persons showed significantly higher rates of HSIL (2%) and unsatisfactory (16%) when compared with the institutional data and atrophic cohort of cisgender women. After reviewing slides of 46 cases, additional findings were noted: atrophy was present in 87%, glycogenated cells were seen in 30%, and Lactobacilli were substantially decreased in 89%. Among 32 available HPV tests, 19% were positive for HR-HPV and 81% were negative. On histologic follow-up, all HR-HPV-positive cases with abnormal cytology showed HSIL, while none of the HPV-negative cases revealed HSIL. Our study cohort demonstrated a high percentage of abnormal Pap tests in transmasculine persons receiving testosterone. Testosterone seems to induce changes in squamous cells and shifts in vaginal flora. HR-HPV testing can be a useful adjunct in the workup of abnormal Pap tests from transmasculine individuals.

ATIPIAS INDETERMINADAS NO DIAGNÓSTICO CITOPATOLÓGICO: UMA REVISÃO DE LITERATURA

Cervical cancer (CC) is one of the most common cancers among women in Brazil. Prevention and early diagnosis are considered the ideal methods to reduce morbidity and mortality rates due to cancer. Diagnosis of CC is performed by Pap smear and the current description of cervical cytology is based on the Bethesda system which results in atypical squamous intraepithelial (ASC), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL). ), squamous cell carcinoma, atypical glandular cells (AGC) and adenocarcinoma. The ASC nomenclature is used to define atypias of indeterminate meaning, however, this generates great concern because it can be used as a way out in situations due to the limitations of the analyst who interprets cervicovaginal cytology. The objective of this paper is to review the existing literature on ASC injuries, describing their clinical importance, such as follow-up procedures and the proposed follow-up protocols. The term ASC requires epithelial changes that are not qualitatively and quantitatively sufficient for a definitive interpretation. The management of patients diagnosed with ASC is not well defined and the most explored option is follow-up with cytopathological examination for 4 to 6 months, immediate colposcopy with biopsy and screening with research for HPV. Defined as the high incidence and mortality of CC, the need to develop studies on indeterminate atypias and the improvement of public policies in primary care, with emphasis on women's health, is evidenced.

The Bethesda System for reporting cervical cytology.

The seminal observations of Dr. George Papanicolaou have grown, through the untiring efforts of many authors, into a universally accepted format of cytology reporting. This has helped immensely to improve the understanding of pathogenesis of cervical cancer. The insights into the complexity of interaction of the etiological and the host factors have further helped in reframing of the reporting system. The Bethesda System (TBS) stands out as a model of standardized reporting in cervicovaginal cytology. Apart from its reproducibility, it reflects the most current understanding of cervical cancer. The most important feature is its clinical relevance. Each category of this classification has clear clinical implications, which are based on solid evidence and worldwide consensus. Moreover, the authors have tried to keep it updated through continuous revisions, incorporating the technological and scientific advances. The component of specimen adequacy reflects the importance it has given to the quality assurance of the laboratory preparation. The minimization of categories, simple terminology, and the supporting image atlas – both in the print form and the web-based form, have made TBS an exemplary teaching-learning resource. The wide accessibility of TBS has been the most important factor in being adopted by a majority of pathology community all over the world.

Influence of tobacco consumption on the appearance of cervicovaginal lesions

The gynecological interrogations, clinical impressions and results obtained from 1587 patients who attended the Department of Cellular Biology of the Faculty of Medicine of the Benemérita Universidad Autónoma de Puebla, México, for cervicovaginal exfoliative cytology sampling (Papanicolaou) were analyzed. Within the framework of the early cancer detection program from March 2010 to March 2021. From the 1587 patients studied, 302 reported smoking during the gynecological examination. Of the total number of patients with a smoking habit 178 (58.94%) showed cervicovaginal lesions on microscopic observation and/or physical examination. Smoking is considered a predisposing factor in the appearance of cervicovaginal lesions, and there is a need to carry out more detailed studies on the secondary effects of tobacco in patients with an active sexual life and a smoking habit in Mexico.