Ruchika Gupta

Performance characteristics of the point-of-care tests for HPV-based cervical cancer screening: a systematic review and meta-analysis

Abstract Background We aimed to conduct an updated and comprehensive summary of the sensitivity and specificity of three human papillomavirus (HPV) point-of-care (POC) tests (careHPV™, oncoE6™ cervical test, Xpert® HPV) to guide resource-constrained countries for their implementation in cervical cancer screening. Methods Databases including Medline, Embase, Web of Science and cumulated index in nursing and allied health literature (CINAHL) were searched between January 2004 and October 2024. Observational studies analyzing the three tests for cervical cancer screening were included. Pooled estimates for the performance characteristics were calculated using random-effect models. Findings Of the 3976 records, 33 studies were included. The sensitivity and specificity of careHPV™ for detection of CIN2+ lesions in self-collected samples were 75.6% and 85.6% compared to 86.4% and 80.4% for physician-collected samples. The sensitivity and specificity of OncoE6™ cervical test were 54.5% and 98.4%, respectively, for physician-collected samples. Xpert® HPV had a sensitivity and specificity of 91.5% and 56.5% in self-collected vaginal samples (SCSs), 92.3% and 53.3%, respectively, in physician-collected cervical samples. Interpretation Both careHPV™ and Xpert® HPV have a good sensitivity and specificity as a POC cervical cancer screening method. These methods also hold potential for use on SCSs. Funding None.

Malignant perivascular epithelioid tumor of the vagina: Report of a rare case with brief review of literature

AbstractPerivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors with immunohistochemical co‐expression of melanocytic and myoid markers. Vaginal PEComas have been described in only nine cases so far. We describe the case of a 65‐year‐old female with a large growth in the left lateral vaginal wall. Biopsy imprint smears showed dispersed tumor cells with anisonucleosis, multinucleation, and bizarre forms, suggestive of a malignant tumor. Histopathology, however, showed perivascular arrangement of clear epithelioid cells, focal necrosis, intracellular brown pigment in few cells, and mitotic activity at 2 to 3 per 50 high power fields. Immunohistochemical positivity for vimentin, HMB‐45, S‐100 protein, desmin, and MyoD1 assisted in rendering a final pathological diagnosis of malignant PEComa of the vagina. Further work‐up revealed metastatic deposits in liver and retroperitoneal lymph nodes. PEComa arising in vagina is an unusual phenomenon with the malignant variant being an extremely rare tumor. Awareness of the characteristic morphology and utilization of a panel of immunohistochemical stains are mandatory to be able to make a precise diagnosis and appropriate prognostication.

Impact of introduction of endocervical brush on cytologic detection of cervical epithelial cell abnormalities: A clinical audit of 13-years’ experience at a cancer research centre

To study the temporal trends in cytologic detection of cervical epithelial cell abnormalities (ECA) and to evaluate the impact of introduction of endocervical brush sampling on detection of ECA. This was a cross-sectional study of conventional cervical smears collected over a 13 year period (2006-2018). The study was divided into two time periods (TP)-TP1 (2006-2014, 67,437 smears) using only extended tip Ayre's spatula and TP2 (2015-2018; 36,746 smears) when Cytobrush Papsmear kit (Ayre's spatula + endocervical brush) was used. The unsatisfactory rate and detection rate of ECA was compared between the two TPs. The unsatisfactory rate reduced from 4.7 % in TP 1-1.5% in TP2 (P < 0.001). The frequency of ECA was 1.5 % in TP1 and 1.9 % in TP2 (P < 0.001). A significantly higher number of ASC-H and HSIL were detected in TP2. There was a substantial improvement (3.7 times) in detection of glandular abnormalities overall (P < 0.001), as also for both the qualifiers AGC- NOS (4.4 times) and AGC- FN (3.3 times) in TP2. Cervical sampling using combined spatula and endocervical brush reduces the unsatisfactory rate and improves the detection of both squamous and glandular precancerous lesions. Hence, this sampling procedure should be recommended for all laboratories practicing conventional cervical cytology.

Reappraisal of cytology‐histology correlation in cervical cytology based on the recent American Society of Cytopathology guidelines (2017) at a cancer research centre

AbstractObjectiveTo assess the impact of recently published American Society of Cytopathology (ASC) guidelines (2017) on the conduct of cervical cytology‐histology correlation (CHC).MethodsA retrospective review was conducted for cervical biopsies with their corresponding conventional cervical smears over a 7.5‐year period (January 2011‐June 2018). As per the ASC guidelines, a discrepancy assessment grid was prepared. Major cytology‐histology discordance was defined as a diagnosis of high‐grade squamous intraepithelial lesion (HSIL) or CIN2+ in one of the tests with negative result in the other. Smears and biopsies of all discordant cases were reviewed for reasons of overcall and undercall.ResultsOf the 341 cervical biopsies with corresponding Papanicolaou smear, cytology‐histology agreement was noted in 249 (73%) cases. Major discordance was observed in 22 cases (6.4%)—16 undercalls and six overcalls on cytology—while minor discrepancies were noted in 70 cases. Atypical metaplasia and repair changes were the main reasons for overcall while small HSIL cells in atrophic smear and scant HSIL cells were important causes of undercall on cytology review. Using the ASC guidelines, we could improvise upon the existing CHC methodology for categorisation of cyto‐histological pairs of cases with a cytological diagnosis of atypical glandular cells.ConclusionThe present study demonstrates, for the first time, that the recent ASC guidelines facilitate cervical CHC, especially for categorisation of cases with atypical glandular cells on cytology. Uniform application of these guidelines would standardise the conduct of cervical CHC internationally and provide scope for inter‐laboratory comparison of data as well as enhance self‐learning and peer learning.

Highly active antiretroviral therapy (HAART) and outcome of cervical lesions and high-risk HPV in women living with HIV (WLHIV): A systematic review and meta-analysis

Collating evidence on the impact of highly active antiretroviral therapy (HAART) on the outcome of cervical lesions or human papillomavirus (HPV) infection among women living with HIV (WLHIV) is essential to inform cervical cancer prevention in this vulnerable group. We performed a systematic review and meta-analysis of cohort studies that were conducted between January 1, 1996 and January 31, 2022 and reported on the association of HAART with any of the outcomes: incidence, progression, or regression of cervical lesions or acquisition or clearance of HPV infection in WLHIV. Random-effect analysis was used for summary statistics and heterogeneity was assessed through I Among 11 studies, the summary estimate of incident cervical lesions was lower in WLHIV on HAART (0.81, 95% CI 0.60-1.08). HAART was associated with lower risk of cervical lesion progression (0.76, 95% CI 0.64-0.92, I This review provides evidence that HAART assists in reducing the incidence and progression of cervical lesions and enhancing their regression in women living with HIV. Hence, the HAART regime should be recommended to all WLHIV with advice for adherence to allow for early immune reconstitution.

High Prevalence of Cervical High-Grade Lesions and High-Risk Human Papillomavirus Infections in Women Living with HIV: A Case for Prioritizing Cervical Screening in This Vulnerable Group

Introduction: Women living with HIV (WLHIV) are at an increased risk of developing cervical precancerous lesions and cervical human papillomavirus (HPV) infection. This study aimed at evaluating the prevalence of cervical lesions and high-risk HPV (HR-HPV) infection in WLHIV in comparison to the HIV-negative women undergoing opportunistic screening. In addition, these findings among WLHIV were correlated with the clinic-demographic factors. Methods: A cross-sectional study was conducted among WLHIVs at a tertiary hospital and linked antiretroviral therapy (ART) center, while HIV-negative women were recruited from the health promotion clinic at our institute. With informed consent, a semi-structured questionnaire was filled on demographic and epidemiological parameters. Conventional cervical smears and samples for HPV DNA detection by HC2 high-risk HPV DNA test were collected in all participants. Cervical smears were reported using the Bethesda system 2014. Appropriate statistical analysis was performed for bivariate and multivariate logistic regression analysis for comparison between WLHIV and HIV-negative women and for correlation of abnormal cervical cytology and HR-HPV infection among WLHIVs. Results: The clinic-demographic characteristics of WLHIVs and HIV-negative women were similar. On cytology, the prevalence of cervical cytological abnormalities were significantly higher (p &lt; 0.001) among WLHIVs (14.1%) compared to HIV-negative women (3.1%). High-grade lesions were seen in 3.7% of WLHIVs, while no high-grade lesions were detected in HIV-negative women. Cervical HR-HPV infection was also significantly higher (p &lt; 0.001) in WLHIVs (28.9%) than HIV-negative women (9.3%). Cervical precancerous lesions in WLHIVs showed positive association with current sexually transmitted infection (STI), multiple sexual partners, tobacco use, and CD4 count less than 200/µL, while cervical HPV was positively associated with current STI, tobacco use, CD4 count less than 200/µL and negatively with ART intake. On multivariate logistic regression, cervical cytological abnormalities showed a significant association with multiple sexual partners (p &lt; 0.001), while cervical HR-HPV infection was positively associated with current STI (p = 0.01), nadir CD4 count &lt;200/µL (p = 0.004), abnormal cervical cytology (p = 0.002) and negatively with ART intake (p = 0.03). Conclusion: Women living with HIV have a significantly higher prevalence of cervical precancerous lesions and HR-HPV infection compared to the general population. Considering the lack of an organized population-based cervical cancer screening program in many low-resource countries like ours, specific focus on screening this highly vulnerable population to reduce the morbidity and mortality due to cervical cancer is imperative.

Knowledge, Practice, and Skills in Cytology-Based Cervical Cancer Screening: Impact Assessment of Training Workshop for the Pathologists

There is a paucity of trained cytopathologists in low-resource settings for effective cervical cancer screening. There has been no documented report of the impact of a dedicated training program in cervical cytology on pathologists' knowledge and skill in this field. The present study aimed to evaluate the efficacy of the regularly conducted training workshops on the attending pathologists' knowledge, practice, and skills in cervicovaginal smear reporting. Our institute, a premier cancer research institute, has conducted 10 cytology-based cervical cancer screening workshops for pathologists with pre- and post-training evaluation using sets of digital images and a questionnaire (knowledge score). Additionally, feedback on diagnostic skills was taken at a 1-month and 6-month interval post-workshop using a separate set of digital images of cervical lesions. A Google form-based questionnaire was designed to seek the participants' feedback on the perceived improvement in knowledge and skills. All the data thus collected were analyzed to assess the efficacy of these workshops in imparting the desired knowledge and skills. A total of 350 participants were enrolled in these workshops. The average knowledge score improved from 10.56 (± 3.23) in the pre-training questionnaire to 21.17 (± 2.41) in the post-training evaluation, making a 100.5% increase (P < 0.001). Similarly, the diagnostic accuracy on digital images was enhanced from 8.6 (± 2.12) to 19.5 (± 4.28) immediately post-training and was maintained at 17.6 (± 3.87) at 1-month and 16.4 (± 4.26) at a 6-month interval (P < 0.001). The majority of the participants reported fair to a marked improvement in their knowledge, practice, and confidence in reporting cervical cytology in the response to form-based questionnaire. One-fifth of the responders also acknowledged the assistance of the knowledge gained during the workshop in refinement or initiation of cervical cytology at their set-up. Our experience of conducting these regular workshops demonstrates the utility of such training programs in human resource development in the field of cervical cytology for enhancement of cervical cancer screening in resource-constrained settings.