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Identifying a blood circulating cellular biomarker that can be used to assess severity of disease and predict the time to culture conversion (TCC) in patients with multidrug resistant tuberculosis (MDR-TB) would facilitate monitoring response to treatment and may be of value in the design of future drug trials. We report on the frequency of blood Ki67 HLA-DR CD4+ T regulatory (Treg) cells in predicting microbiological outcome before initiating second-line treatment for MDR-TB. Fifty-one patients with MDR-TB were enrolled and followed over 18 months; a subset of patients was sputum culture (SC) negative at baseline ( = 9). SC positive patients were divided into two groups, based on median TCC: rapid responders (≤71 days TCC; = 21) and slow responders (>71 days TCC; = 21). Whole blood at baseline, months 2 and 6 was stimulated with M tuberculosis (Mtb) antigens and Treg cells were then identified as CD3 CD4 CD25 FoxP3 CD127 CD69 and further delineated as Ki67 HLA-DR Treg. The frequency of these cells was significantly enlarged at baseline in SC positive relative to SC negative and smear positive relative to smear negative patients and in those with lung cavitation. This difference was further supported by unsupervised hierarchical clustering showing a significant grouping at baseline of total and early differentiated memory Treg cells in slow responders. Conversely, there was a clustering of a lower proportion of Treg cells and activated IFNγ-expressing T cells at baseline in the rapid responders. Examining changes over time revealed a more gradual reduction of Treg cells in slow responders relative to rapid responders to treatment. Receiver operating curve analysis showed that baseline Mtb-stimulated Ki67 HLA-DR Treg cells could predict the TCC of MDR-TB treatment response with 81.2% sensitivity and 85% specificity (AUC of 0.87, < 0.0001), but this was not the case after 2 months of treatment. In conclusion, our data show that the frequency of a highly defined Mtb-stimulated blood Treg cell population at baseline can discriminate MDR-TB disease severity and predict time to culture clearance.

Abstract Objectives In another publication, we concluded endocervical curettage (ECC) should have a minimum number of squamous cells for adequacy, similar to the requirements for adequate cervical Papanicolaou smears. Here, we investigate if also, similar to cervical Papanicolaou smears, the presence of at least 10 cells from the endocervical/transformation zone (EC/TZ) in ECCs should be used as a quality assurance measure or if, instead, at least 10 EC/TZ cells should be part of the adequacy criteria for ECC, with an emphasis on diagnosis of at least high-grade squamous dysplasia (HGD). Methods All patients with at least HGD diagnosed on an excisional biopsy specimen (loop electrosurgical excision procedure [LEEP]) from May 1, 2018, to December 31, 2019, and an ECC in the preceding 6 months at our institution were included. Number of EC/TZ cells present in ECCs was counted visually and categorized as less than or greater than 10 TZ cells. A χ2 test was used to evaluate the proportion of ECCs with and without HGD and the presence or absence of at least 10 EC/TZ cells. Given our recent work encouraging at least 1000 squamous cells in an ECC to be considered adequate, we also evaluated only ECCs with greater than 1000 squamous cells with and without HGD and the presence or absence of at least 10 EC/TZ cells. P value was <.05. Results Fifty-one LEEPs with HGD and a preceding ECC in the previous 6 months were identified. Of the 51 ECCs, 6 had fewer than 10 EC/TZ cells and 45 had at least 10 EC/TZ cells. A similar proportion of the ECCs with HGD had at least 10 EC/TZ cells as those without HGD (93% vs 86%, P = .53). Using only ECCs with greater than 1000 squamous cells, we still found no statistical difference in the proportion of ECCs with HGD having greater than 10 EC/TZ cells compared to those without HGD (91% vs 100%, P = .49). Conclusions We found that the presence of at least 10 EC/TZ cells does not increase the likelihood of finding HGD in an ECC performed in the 6 months prior to a LEEP with HGD. Similar to the use of the TZ component in cervical Papanicolaou smears, the presence or absence of at least 10 TZ cells in an ECC should only be considered a quality assurance measure and not be used as a criterion for adequacy of the specimen.

Background and Objectives: In women who are positive for high-risk human papillomavirus (hrHPV), abnormal cytology necessitates colposcopy and biopsy; however, cytology–histology concordance is variable and may differ by menopausal status. This study aimed to evaluate the concordance between cytologic findings and biopsy results in hrHPV-positive women with abnormal Pap tests and to compare outcomes by menopausal status. Materials and Methods: This retrospective, single-center study included 904 hrHPV-positive women with abnormal cytology who underwent colposcopy. Cytology findings [atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells—cannot exclude high-grade squamous intraepithelial lesion (ASC-H), and high-grade squamous intraepithelial lesion (HSIL)] were compared with histological findings [normal, cervical intraepithelial neoplasia (CIN)-1, -2, -3]. Menopausal status was stratified as premenopausal (<48 years) and postmenopausal (≥48 years). Rates of cyto-histologic concordance, overestimation, and underestimation were calculated. Results: The predominant cytological result was ASC-US (61.7%), followed by LSIL (25.3%), whereas histologically, CIN was most common (66.5%; CIN-1: 42.8%, CIN-2: 11.5%, CIN-3: 12.2%). Cytology–biopsy concordance was 50.7%, with overestimation in 35.4% and underestimation in 13.9%. Overestimation was highest in ASC-US (43.9%) and ASC-H (37%), while underestimation was most frequently seen in LSIL cases (27.1%). HSIL cytology showed the highest agreement (85.7%). Conversely, LSIL cytology showed higher cyto-histologic concordance in postmenopausal women, whereas ASC-H and HSIL cytologies were more commonly overestimated in comparison to premenopausal women. Using ASC-H/HSIL as the positive cytology threshold for CIN-2+ detection, sensitivity was 41.1% and specificity was 95.8% [positive predictive value (PPV) 75.2%, negative predictive value (NPV) 84.0%; overall accuracy 82.9%]. The sensitivity and NPV were higher in postmenopausal women than in premenopausal women (50.0% vs. 39.9%; 91.3% vs. 82.3%, respectively). Conclusions: Cytology–histology concordance is moderate among women who are hrHPV-positive with abnormal cytology, characterized by notable underestimation in low-grade cytology and strong predictive value in HSIL cases. Menopausal status influences the outcomes; in postmenopausal women, high-grade lesions are less frequent, and diagnostic accuracy for detecting CIN-2+ is higher. These findings highlight the need for age- and menopause-sensitive diagnostic approaches.

Background Uganda has approximately 1.2 million people aged 15–64 years living with human immunodeficiency virus (HIV). Previous studies have shown a higher prevalence of premalignant cervical lesions among HIV-positive women than among HIV-negative women. Additionally, HIV-infected women are more likely to have human papilloma virus (HPV) infection progress to cancer than women not infected with HIV. We determined the prevalence of premalignant cervical lesions and their association with HIV infection among women attending a cervical cancer screening clinic at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. Methods We conducted a comparative cross-sectional study of 210 women aged 22–65 years living with HIV and 210 women not living with HIV who were systematically enrolled from March 2022 to May 2022. Participants were subjected to a structured interviewer-administered questionnaire to obtain their demographic and clinical data. Additionally, Papanicolaou smears were obtained for microscopy to observe premalignant cervical lesions. Multivariate logistic regression was performed to determine the association between HIV status and premalignant cervical lesions. Results The overall prevalence of premalignant cervical lesions in the study population was 17% ( n  = 72; 95% C.I: 14.1–21.4), with 23% ( n  = 47; 95% C.I: 17.8–29.5) in women living with HIV and 12% ( n  = 25; 95% C.I: 8.2–17.1) in women not living with HIV ( p  < 0.003). The most common premalignant cervical lesions identified were low-grade squamous intraepithelial lesions (LSIL) in both women living with HIV (74.5%; n  = 35) and women not living with HIV (80%; n  = 20). HIV infection was significantly associated with premalignant lesions (aOR: 2.37, 95% CI: 1.27–4.42; p  = 0.007). Conclusion Premalignant cervical lesions, particularly LSILs, were more common in HIV-positive women than in HIV-negative women, highlighting the need to strengthen the integration of cervical cancer prevention strategies into HIV care programs.

PurposeThe aims of the present study were to evaluate the development of untreated cervical intraepithelial neoplasia (CIN) 3 during pregnancy and to assess persistence, progression, and regression rates postpartum to identify factors associated with regression.MethodsIn a tertiary gynecology and obstetrics department, a total of 154 pregnant women with CIN 3 were treated in the dysplasia unit. The follow-up findings were analyzed retrospectively on the basis of histological, cytological, and human papillomavirus (HPV) testing of 154 pregnant women confirmed as having CIN 3 in colposcopically guided biopsies.ResultsThe rates of persistence, regression, and progression of CIN 3 in these women were 76.1%, 20% and 3.2%, respectively. Data for the delivery mode was available for 126 women. The rate of regression was almost twice as high with vaginal delivery as with cesarean section, at 27.4 vs. 15.2%, whereas the rate of progression was lower with vaginal delivery, at 2.7 vs. 6.5%.ConclusionThe rate of persistence of CIN observed in this study is comparable to that reported in other studies. The study provides strong evidence for greater regression among women who have vaginal deliveries. Careful work-up is recommended postpartum for this group of women in order to rule out persistent CIN 3 or invasive disease.

Cervical cytology is a vital screening tool used to detect precancerous and cancerous cells in the cervix. The procedure is crucial in preventing cervical cancer by enabling the early detection and treatment of abnormal cells. In the context of pregnancy, cytology remains an essential component of prenatal care. Numerous studies confirmed that cytology was safe for both the mother and the fetus when performed correctly. The interpretation of cytological results during pregnancy requires careful consideration due to physiological changes in the cervix, which may mimic or obscure pathological findings. The review describes physiological changes in cervical cytology during pregnancy, interpretation challenges and the guidelines of international societies in this topic.

Background and Objectives: Cotesting combines cervical cytology and HPV testing and usually identifies HSIL/ASC-H in association with HPV positivity; however, a small subset shows discordant results with high-grade cytology but negative HPV testing. We evaluated the clinicopathologic significance and histologic outcomes of HPV-negative HSIL or ASC-H cytology in a tertiary referral setting. Materials and Methods: We retrospectively reviewed women referred to a tertiary colposcopy unit (January 2019–October 2025) with HPV-negative HSIL or ASC-H on cotesting. Clinical findings, colposcopy, histology, excisional procedures, and follow-up were abstracted. Cytology and histology were reviewed by an expert gynecologic pathologist, and p16 immunohistochemistry was performed in all cases. Results: Among 92 women with HSIL/ASC-H cytology who underwent cotesting, 84 were HPV-positive (35 HSIL, 49 ASC-H). Eight cases (8.7%) remained HPV-negative after cytology review: 2/37 (5.4%) HSIL and 6/55 (10.9%) ASC-H. On histology, 4/8 (50%) had HSIL (CIN3) and 4/8 had LSIL; all CIN3 cases showed diffuse block-type p16 positivity. Two of six HPV-negative ASC-H cases (33.3%) were CIN3. One patient had persistent high-grade disease requiring two excisional procedures during follow-up. Conclusions: HPV-negative HSIL/ASC-H cytology is uncommon but associated with a substantial risk of CIN3. The consistent p16 positivity in tissue-confirmed HSIL supports HPV-attributable disease and suggests that most discordant cases reflect false-negative HPV testing rather than HPV-independent pathology. High-grade cytology should prompt colposcopic evaluation regardless of HPV status, and management should not be de-escalated solely on the basis of a negative HPV test.

Objective This study aims to analyse high‐grade intraepithelial lesions (LIEHG) observed in a screening programme from 2010 to 2018 to more accurately describe them and formulate recommendations for best practices in the context of screening evolution following the introduction of an HPV test in primary cervical cancer screening in 2020. Methods This study included 305,940 asymptomatic women aged 25–65 years. The eligible population was invited to undergo a screening cervico‐uterine‐smear every 3 years. If this smear was normal, the woman received a new invitation. In the case of a positive screen, the patient underwent further diagnostic procedures, such as colposcopy and biopsy to confirm the diagnosis. Only those diagnosed with LIEHG and above proceeded to treatment. The diagnoses associated with LIEHG were those related to the WHO Classification of tumours of the uterine cervix. Results Positive smears led to the diagnosis of 3230 LIEHG. The prevalence of LIEHG in the screened population was 0.4%. The LIEHG distribution varied significantly according to the age of the women. The probability of diagnosing LIEHG in young women was 12.2% at 25–29 years. This probability decreased by half after 50 years. We observed that the type of smear was significantly associated with LIEHG detection. The positive predictive value for diagnosing LIEHG was 70.3% for high‐grade squamous intraepithelial lesion (HSIL) smears and 35.1% for atypical squamous cells cannot exclude HSIL (ASC‐H) smears. Conclusion In the study population, the prevalence of LIEHG was high in women under 35 years. Low‐grade smears were correlated with the risk of LIEHG and should prompt screening facilities to allocate resources to ensure active follow‐up of LSIL and ASC‐US smears. Adherence to cytological screening recommendations was associated with a reduced risk of LIEHG in multivariate analysis. At the time of the data extraction 732,203 cervico‐uterine‐smears had been performed on 305,940 women. The number of first positive smear observed in each woman was retained in the analysis: 31,097 cases. These positive smears led to the diagnosis of 3,230 LIEHG.

Background Atypical glandular cells, favor neoplastic (AGC-FN) identified in Papanicolaou (Pap) smears may be indicative of pre-malignant and malignant cervical and endometrial lesions. However, an effective strategy for triaging patients with AGC-FN remains elusive. This study aimed to analyze the relationship between AGC-FN and high-grade lesions, as well as identify specific risk factors which can optimize the currently strategy in women with AGC-FN. Methods This retrospective utilized data from the China’s Fujian Cervical Pilot Project (FCPP). A total of 211 women diagnosed with AGC-FN according to the Bethesda 2014 classification system underwent follow-up through colposcopy, biopsy, and endometrial curettage between January 2013 and July 2021. The association between high-grade lesions and clinicopathologic features were analyzed using independent sample nonparametric tests and binary logistic regression. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of different triage strategie were evaluated. Results There were 43.60% (92/211) and 27.96% (59/211) AGC-FN women diagnosed as ≥ endometrial precancerous lesions (≥ EPL) and CIN2 + , respectively. In women with ≥ EPL, the top 3 risk factors were higher HE4, higher CA125 and older age (adjusted odds ratio [OR adjusted ]: 3.351, 2.760, 1.124, all p  < 0.05, respectively). The top 3 risk factors for ≥ HISL women were HPV-16/18 infection, HPV-16/18/58/59 infection and HR-HPV infection (OR adjusted : 50.122, 40.043, 37.011, all p  < 0.01, respectively). Interestingly, the age, CA125 and HR-HPV infection showed opposite roles in AGC-FN women with ≥ EPL and ≥ HISL. When using ≥ EPL and ≥ HISL as endpoints, strategies 2 and 4 had the highest sensitivities of 97.3% and 95.3% and highest NPV of 80.0% and 97.3% by incorporating specific risk factors, respectively. Moreover, the referral rates of strategies 1, 3 and 4 were significantly lower (76.5%, 38.0% vs 62.8%, p  < 0.05). Conclusion CA125 and HR-HPV infection emerged as significant risk factors for triaging women with AGC-FN and HPV-16 and -18, HPV-58 and -59 infections should not to be overlooked. A novel triage strategy combining CA125, CA199, HE4 and HR-HPV reduced the referral rates of biopsy and curettage without altering the original sensitivity.

Background This study examined the viral load and physical status of the human papillomavirus 16 (HPV-16) genome in non-cancerous, precancerous and cancerous cervical lesions. Methods Quantitative real-time PCR was performed to determine HPV-16 E2 and E6 viral load in 132 cervical specimens. E2/E6 viral load ratio was used to determine the physical status of HPV-16 genome. Results E2 gene viral load was a significant (P < 0.001) predicting biomarker in differentiating non-cancerous from precancerous and cancerous samples. E6 gene viral load was significantly different between the groups (P < 0.001). The specificity and sensitivity of E2 and E6 in distinguishing SCC samples were 100% and 95% respectively. Conclusion HPV-16 viral load measured through E2 and E6 genes is a reliable indicator of lesion type.