Cervix Research Articles

Comparison of classical and anchorage methods in sacrospinous ligament fixation

Aims: Pelvic organ prolapse (POP) is a common condition that affects the quality of life in women. As a natural consequence of the aging population, it is believed that POP will increase in the next 40 years. With the increase in life expectancy, there is an expected rise in reconstructive surgical procedures to correct pelvic floor disorders. POP can occur in three vaginal compartments: anterior, apical, and posterior. The apical compartment includes uterine prolapse, cervix, or vaginal cuff prolapse. Our primary objective was to compare the surgical outcomes of the method using the classic technique with pelvic floor anchorage (anchoring). Methods: This retrospective cohort study consisted of women with POP-Q (Pelvic Organ Prolapse Quarejment) grade 2 and above in the apical compartment. In the sample size calculation, G power analysis was performed with α: 0.05 and 80% accuracy. Forty-eight women were included in the study, with 24 of them undergoing the classic method and the other 24 receiving sacrospinous ligament fixation (SSLF) using a pelvic floor anchoring device. The results of both surgical methods were compared in terms of anatomical recurrence. Results: There was no statistically significant difference observed between the postoperative measurements of the C points. However, the difference in the C level between preoperative and postoperative measurements for patients who underwent the classic SSLF operation was statistically significantly higher compared to those who underwent the Anchorage SSLF procedure. Conclusion: When comparing the classic and anchoring systems for the SSLF procedure, no difference was observed in terms of recurrence. However, the classic method was found to be more successful in restoring apical prolapse.

Whole-exome Sequence Analysis of Gastric-type Adenocarcinoma of the Uterine Cervix and Adjacent Lobular Endocervical Glandular Hyperplasia in the Same Case.

Lobular endocervical glandular hyperplasia (LEGH) may be a precursor lesion of gastric-type adenocarcinoma of the uterine cervix (GAS). However, the genetic mechanisms underlying its carcinogenesis remain unclear. To elucidate the oncogenic process from LEGH to GAS, we compared gene mutations in early-stage GAS and adjacent LEGH in the same case. Fresh-frozen tissue sections were obtained from a patient with Stage IB3 GAS and adjacent LEGH who had undergone hysterectomy. Using laser microdissection, we harvested the LEGH and GAS portions separately from these sections and extracted the genomic DNA. Somatic variant analysis using whole-exome sequencing used DNA from the normal myometrium as a reference sequence. Somatic variants involving amino acid substitutions were detected in 61 and 125 locations in LEGH and GAS, respectively. Seven variants were common in both lesions, of which the pathogenic variant was GNAS only (c.2531G>A, p.R844H), a mutation frequently reported in pancreatic and colorectal cancers. LEGH had no other pathogenic variants; another pathogenic variant in GAS was found only at the same amino acid site as GNAS (c.2530C>T, p.R844C). In the present case, LEGH and GAS shared the same pathogenic variant of GNAS, indicating that both lesions had a common origin. Furthermore, the current results showed that the second GNAS variant is associated with the progression of LEGH to GAS. Further studies are required to elucidate GAS's pathogenesis and biological characteristics.

Exploring uterine involvement in hysterectomy samples following conization for adenocarcinoma in situ of the uterine cervix: Insights from a multicenter study by the FRANCOGYN group

BackgroundAdenocarcinoma in situ (AIS) of the cervix can progress to invasive adenocarcinoma. While hysterectomy is standard, conservative management may be considered for women desiring future pregnancies. This study aimed to determine the prevalence of residual disease in hysterectomy specimens following excisional therapy with clear margins for AIS. MethodsA retrospective FRANCOGYN cohort study was conducted on patients who underwent a hysterectomy after conization with clear margins for AIS between 2008 and 2021. The primary goal was to assess the prevalence of residual disease in the hysterectomy specimens. Secondary objectives included identifying preoperative predictors of residual disease and comparing recurrence rates between patients with and without residual disease. ResultsOf 53 hysterectomies performed after conization with negative margins for AIS, 20.8% (11/53) showed residual disease in the final histology. None of the patients had invasive cancer. In the residual disease group, 18% (2/11) had persistent CIN 3, and 82% (9/11) had persistent AIS. These patients tended to have higher BMI (27.5 kg/m² vs. 23.6 kg/m², p=0.04) and shorter endocervical margins (2mm vs. 5mm, p=0.01). No recurrences were observed during follow-up. ConclusionDespite clear margins on the initial conization for AIS, 20% of patients had residual disease in their hysterectomy samples, though no invasive cancer was found. A hysterectomy should be considered after completing childbearing, even if initial margins are clear.

Expanding management strategies for cervical precancerous lesions in resource-limited settings: insights from a training center in a district hospital in Ghana

BackgroundCervical cancer continues to disproportionately burden women in low/middle-income countries like Ghana. We examined treatment patterns and histopathological outcomes among women screened using visual inspection with acetic acid (VIA) and/or mobile colposcopy who subsequently underwent thermal ablation, large loop excision of the transformation zone (LLETZ), or cold knife conization at the Cervical Cancer Prevention and Training Centre, Battor. We also assessed the prevalence of cervical intraepithelial neoplasia 2+ (CIN2+) or micro-invasive disease and their associated factors for women who underwent excisional treatments. The treatment choices for cervical precancerous lesions suitable for resource-limited settings have also been described from the perspective of a center that manages a heterogenous population.MethodsWe conducted an analysis of secondary data collected between June 2016 and June 2023 among women with positive findings on VIA or mobile colposcopy who subsequently underwent thermal ablation or large loop excision of the transformation zone (LLETZ). The prevalence of histopathology outcomes, including no dysplasia, CIN1 − 3, and micro-invasive disease, were estimated with 95% confidence intervals (CIs). Factors associated with histopathological findings were modeled using multinomial logistic regression.ResultsFor the study period, 14 (10.6%) of the total 132 participants underwent cervical lesion treatment at outreach locations, all via thermal ablation. The remaining 118 (89.4%) were treated at the Catholic Hospital, Battor using LLETZ (n = 66, 55.9%), thermal ablation (n = 51, 43.2%), and cold knife conization (n = 1, 0.9%). Among 65 women with histopathology reports, the most frequent histopathological finding was no dysplasia (47.7%; 95% CI, 35.1 − 60.5), followed by CIN2 and CIN3 (20.0%; 95% CI, 11.1 − 31.8 each), CIN1 (7.7%; 95% CI, 2.5 − 17.0) and micro-invasion (4.6%; 95% CI, 1.0 − 12.9). Those with micro-invasive disease were significantly older than those with CIN1, CIN2, and CIN3 (p = 0.036, 0.022, 0.009, respectively), but not significantly older than those who showed no dysplasia (p = 0.088). For each unit increase in age, the likelihood of CIN3 was relatively significantly reduced compared to no dysplasia (crude relative risk ratio [RRR] = 0.93; 95% CI, 0.86 − 0.99). This association was neither observed with the remaining histopathological groups nor for parity and persisted after controlling for parity (adjusted RRR = 0.92; 95% CI, 0.85 − 0.99; p = 0.025).ConclusionThis paper largely demonstrates treatment options available to women and practitioners in LMICs. The high combined prevalence of high-grade precancerous lesions and micro-invasive disease underscores the need to increase cervical cancer awareness that would enhance screening attendance and hasten efforts at moving from opportunistic to organized screening in Ghana. This will enhance early cervical lesion detection and treatment, while simultaneously re-evaluating and cutting down on unnecessary treatment.

Issues in the treatment of cervix uteri

Issues in the treatment of cervix uteri

Role of Neoadjuvant Chemotherapy in High-Grade Neuroendocrine Carcinoma of the Uterine Cervix

Role of Neoadjuvant Chemotherapy in High-Grade Neuroendocrine Carcinoma of the Uterine Cervix

Immediate risk of cervical intraepithelial neoplasia and diagnostic value of colposcopy among cytology-negative women with oncogenic HPV: a retrospective study

BackgroundCervical cancer screening results that are negative for cytology but positive for high-risk human papillomavirus (HR-HPV) are not uncommon. One-year follow-up is suggested for patients with no history of HPV positivity under the most recent American Society of Colposcopy and Cervical Pathology (ASCCP) guidelines (2019). The aim of this study was to evaluate the immediate risk of cervical intraepithelial neoplasia (CIN) among cytology-negative patients positive for HR-HPV. The diagnostic accuracy of colposcopy in these patients was investigated.MethodsA retrospective study was conducted in patients who were cytology negative but HR-HPV positive and referred for colposcopy from January 2022 to August 2023. Patients were compared in terms of the immediate rate of CIN lesions among the HPV16-positive group, the HPV18-positive group and the non-16/18 HR-HPV-positive group. The distribution of CIN2 + lesions according to age was evaluated. The factors associated with the accuracy of colposcopy were evaluated using univariate and multivariate logistic regression.ResultsAmong the 372 patients, 195 had chronic cervicitis, 131 had CIN1, 37 had CIN2/3, and nine had carcinoma. The immediate rates of CIN2 + lesions and CIN3 + lesions in patients who were not HR-HPV16/18-positive were comparable to those in patients who were HPV16/18-positive (P = 0.699). In addition, among patients diagnosed with CIN2 + lesions, 8 (17.39%) patients were women aged < 30 years. When pathological results were used as a reference, the consistency rate of colposcopy was 61.0% (227/372). Multivariate analyses revealed that age and the type of cervical transformation zone were independent factors affecting the accuracy of colposcopy (P < 0.001).ConclusionsIn countries with limited resources, immediate colposcopy referral should be recommended for patients who are cytology negative but HR-HPV-positive (including non-16/18 HR-HPV-positive), and cervical cancer screening via cotesting should be suggested for women aged < 30 years. Colposcopy has moderate diagnostic value and can be affected by age and the type of cervical transformation zone.

Traditional Chinese Medicine Erhuang Suppository for Treatment of Persistent High-risk Human Papillomavirus Infection and Its Impact on Transcriptome of Uterine Cervix.

High-risk human papillomavirus (HR-HPV) infection is the chief cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. The Erhuang suppository (EHS) is a traditional Chinese medicine (TCM) prepared from realgar (As2S2), Coptidis rhizoma, alumen, and borneolum syntheticum and has been used for antiviral and antitumor purposes. However, whether EHS can efficiently alleviate HR-HPV infection remains unclear. This study was conducted to evaluate the efficacy of EHS for the treatment of persistent HR-HPV infection in the uterine cervix. In this study, we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up. Totally, 70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo. HPV DNA, ThinPrep cytologic test (TCT), colposcopy, and safety evaluation were carried out after treatment. Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment. A K14-HPV16 mouse model was generated to confirm the efficiency of EHS. After 3 months, 74.3% (26/35) of the patients in the treatment group were HPV negative, compared to 6.9% (2/29) in the placebo group. High-throughput microarrays revealed distinct transcriptome profiles after treatment. The differentially expressed genes were significantly enriched in complement activation, immune response, and apoptotic processes. The K14-HPV16 mouse model also validated the remarkable efficacy of EHS. This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions. Additionally, no obvious systemic toxicity was observed in patients during the trial. The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases.

Impact of MRI radiomic feature normalization for prognostic modelling in uterine endometrial and cervical cancers

Widespread clinical use of MRI radiomic tumor profiling for prognostication and treatment planning in cancers faces major obstacles due to limitations in standardization of radiomic features. The purpose of the current work was to assess the impact of different MRI scanning- and normalization protocols for the statistical analyses of tumor radiomic data in two patient cohorts with uterine endometrial-(EC) (n = 136) and cervical (CC) (n = 132) cancer. 1.5 T and 3 T, T1-weighted MRI 2 min post-contrast injection, T2-weighted turbo spin echo imaging, and diffusion-weighted imaging were acquired. Radiomic features were extracted from within manually segmented tumors in 3D and normalized either using z-score normalization or a linear regression model (LRM) accounting for linear dependencies with MRI acquisition parameters. Patients were clustered into two groups based on radiomic profile. Impact of MRI scanning parameters on cluster composition and prognostication were analyzed using Kruskal–Wallis tests, Kaplan–Meier plots, log-rank test, random survival forests and LASSO Cox regression with time-dependent area under curve (tdAUC) (α = 0.05). A large proportion of the radiomic features was statistically associated with MRI scanning protocol in both cohorts (EC: 162/385 [42%]; CC: 180/292 [62%]). A substantial number of EC (49/136 [36%]) and CC (50/132 [38%]) patients changed cluster when clustering was performed after z-score-versus LRM normalization. Prognostic modeling based on cluster groups yielded similar outputs for the two normalization methods in the EC/CC cohorts (log-rank test; z-score: p = 0.02/0.33; LRM: p = 0.01/0.45). Mean tdAUC for prognostic modeling of disease-specific survival (DSS) by the radiomic features in EC/CC was similar for the two normalization methods (random survival forests; z-score: mean tdAUC = 0.77/0.78; LRM: mean tdAUC = 0.80/0.75; LASSO Cox; z-score: mean tdAUC = 0.64/0.76; LRM: mean tdAUC = 0.76/0.75). Severe biases in tumor radiomics data due to MRI scanning parameters exist. Z-score normalization does not eliminate these biases, whereas LRM normalization effectively does. Still, radiomic cluster groups after z-score- and LRM normalization were similarly associated with DSS in EC and CC patients.

Label-free assessment of the transformation zone using multispectral diffuse optical imaging toward early detection of cervical cancer.

The assessment of the transformation zone is a critical step toward diagnosis of cervical cancer. This work involves the development of a portable, label-free transvaginal multispectral diffuse optical imaging (MDOI) imaging probe to estimate the transformation zone. The images were acquired from N = 5 (N = 1 normal, N = 2 premalignant, and N = 2 malignant) patients. Key parameters such as spectral contrast ratio (ρ) at 545 and 450 nm were higher in premalignant (0.29, 0.25 for 450 nm and 0.30, 0.17 for 545 nm) as compared to the normal patients (0.13 and 0.14 for 450 and 545 nm, respectively). The threshold for the spectral intensity ratio R610/R450 and R610/R545 can also be used as a marker to correlate with the new and original squamous columnar junction (SCJ), respectively. The pilot study highlights the use of new markers such as spectral contrast ratio (ρ) and spectral intensity ratio (R610/R450 and R610/R545) images.

Diagnostic cervical excision in patients with HPV positivity, cytological abnormalities- and preoperative cervical stenosis

AimThere is currently no protocol for classifying patients with HPV persistence and preoperative stenosis of the cervical canal. This has a significant impact on cytology results, colposcopy results and the possibility of obtaining reliable cervical histology outcomes. Our analysis clearly shows that colposcopy and cytology underestimate the histological results in patients with limited visibility due to the presence of a type 3 transformation zone (TZ). Our analysis revealed a significant discrepancy between the colposcopy and cytology results and the histological outcomes. Insufficient colposcopy led to the underdiagnosis of dysplastic lesions in patients with a type 3 TZ and cervical stenosis. In the case of repeated cytological abnormalities and inadequate colposcopy examination, it is crucial to perform a diagnostic conization to exclude high-grade dysplastic changes and cervical carcinoma.MethodsWe conducted a retrospective analysis of 1,021 conizations performed in tertiary care hospital in Wolfsburg, Germany between 2014 and 2020. Of these surgical procedures, 89 were diagnostic conizations. In our analysis, we defined diagnostic conization as a procedure performed when there is HPV persistence and repeated cytologic abnormalities in combination with a type 3 TZ, and when it is not possible to retrieve a relevant cervical histology sample.ResultsIn this period, 8.7% of all conizations were diagnostic excisions. We found histological abnormalities in 48 of 89 patients (53.9%). The histological examination of the excised cone revealed high-grade cervical intraepithelial neoplasia (CIN/HSIL) in 9 patients (10.1%) and CIN 2+ (HSIL) in 23 out of the 89 patients (25.8%). Two cases of early-stage cervical carcinoma (FIGO IA1 and FIGO IA2) were confirmed (2.3%).ConclusionPatients with cervical stenosis, high-risk HPV persistence and repeated cytological abnormalities are at high risk of undetected high-grade cervical dysplasia. Histologic confirmation must be ensured in this patient consultation and this can be achieved by performing diagnostic excisions.

The Rare Condition of a Double Cervix: Results from the High-Risk Human Papillomavirus-Based Cervical Cancer Screening Program in the Lazio Region.

Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of high-risk (HR)-HPV infection in the female population has led to the discovery of several cases of a double cervix, a congenital malformation that is very rare. The purpose of this study was to evaluate HR-HPV infections in women with a double cervix within the National Cervical Cancer Screening program of the Lazio region (Italy). From June 2021 to March 2024, a total of 142,437 samples were analyzed by Seegene's Anyplex TM II HR-HPV method, which identifies 14 HR-HPV genotypes. For each woman identified with a double cervix, two separate samples were taken from both cervices and analyzed separately. Twenty-seven women with a double cervix were identified (0.019%): 23 women were tested as negative for both cervices, while the remaining four (namely A, B, C, and D) resulted positive. By genotyping, the following results were obtained: (A) Both samples showed genotype 31; (B) one cervix was negative while the other showed genotype 58; (C) one cervix was positive for HPV 18 and 31 while for 18, 31, and 33 in the other; and (D) one cervix showed genotype 66 while the other carried the 66 and 68 genotypes. Double cervix is a very rare condition where the presence of HR-HPV genotypes is not homogeneous. As already described, our study confirms that different genotypes can be detected in double cervix malformation, suggesting the need to perform HPV screening on brushing samples from both cervices.

Prognostic Importance of 18F-FDG Positron Emission Tomography in Uterine Cervical Cancer.

The aim of this study was to evaluate the prognostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the uterine cervix cancer patients. Thirty-two women (mean age: 52.7±12.6) who underwent 18F-FDG PET/CT for staging of uterine cervix cancer were retrospectively recruited for the study. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumors, lymph nodes, and distant metastases were calculated from 18F-FDG PET/CT images using the 40% threshold. Patients were divided into groups according to the presence of pelvic and para-aortic lymph node involvement on 18F-FDG PET/CT images. Life tables and Kaplan-Meier analyses were performed to compare the mean survival times of the different groups. Primary tumor of 27 (84%) patients were 18F-FDG avid. The median SUVmax, SUVmean, MTV, and TLG of the primary tumors were 12.4, 6.1, 13.2 cm3 and 87.8 g/mL x cm3 respectively. Pathological uptake was detected in pelvic 14 (44%) patients and in paraaortic lymph nodes in 3 (10%) para-aortic lymph nodes. The median whole-body MTV and TLG were 21.7 cm3 and 91.1 g/mL x cm3. Disease progression was detected in 7 (22%) patients within a median follow-up period of 20.9 (minimum-maximum: 3-82) months. The only significant PET parameter to predict progression-free survival was SUVmax in the primary tumor (p=0.038). During follow-up period 8 patients died. SUVmax (p=0.007), MTV (p=0.036), TLG (p=0.001) of primary tumor, presence of pathological uptake on pelvic or paraaortic lymph nodes (p=0.015), whole-body MTV (p=0.047) and whole-body TLG (p=0.001) were found statistically significant PET parameters to predict overall survival. Metabolic parameters of primary tumors derived from 18F-FDG PET/CT images have prognostic importance for patients with uterine cervical carcinoma. In patients with metastatic disease, higher whole-body MTV and TLG are also associated with poor prognosis.

Fertility-sparing strategy in a rare case of highly malignant Dicer-1-associated sarcoma of the cervix

IntroductionWe present the rare case of an 18-year-old patient with a Dicer-1 mutation-associated sarcoma of the cervix uteri.CaseThe patient presented with irregular vaginal bleeding in July 2022. The clinical examination showed an exophytic tumor of the cervix, uterus and ovaries were normal in sonogram. The tumor of the cervix was resected, followed by a diagnostic hysteroscopy and abrasion of the uterine cervix and cavity. Hysteroscopy showed normal findings of the cervix and uterus. After diagnosis of a highly malignant Dicer-1 mutation-associated sarcoma of the cervix, cryopreservation of oocytes was realized. Based on the principle of obtaining maximum oncological safety while preserving fertility in this 18-year-old patient, we recommended chemotherapy rather than radiation with its far severe implications on the patient´s reproductive organs. 4 cycles of chemotherapy consisting of doxorubicin and ifosfamide were applied until December 2022. After re-staging in December 2022 via CT scan and MRI, the abdomen and pelvis as well as control hysteroscopy and abrasion were unremarkable. Until now, the patient is tumor free.DiscussionPrimary sarcomas of the cervix are very rare. Recent literature hints towards a distinct DICER-1 sarcoma entity characterized by specific mutational clusters. Limited follow-up data suggested that DICER1-mutant tumors might exhibit a less aggressive clinical course than DICER1-wild-type tumors.ConclusionDecision-making in case of rare histological entities with sparse recommendations in the literature poses a challenge to the treating physician. Treatment strategies should consider oncological safety as well as options of preserving fertility. Gonadotoxic potential of different strategies should be taken into consideration and discussed in detail with the affected patient.

P-209 Development and characterization of human uterine myometrium in prenatal stage: insights from a single-cell atlas and three-dimensional imaging

Abstract Study question What’s the timepoint of human uterine myometrial formation and how dose it develop in the prenatal stage. Summary answer This study identified that the myometrium layer initially forms at postconceptional week (PCW) 11, ESR1+, IGFBP5, POSTIN may play pivotal role in myometrial development. What is known already Using immunohistochemistry staining, previous studies observed a faint expression of α-SMA in the outer mesenchyme at approximately 8-9 weeks of gestation and showed the early development of muscular layer in the uterine wall, and the expression of α-SMA becomes more prominent in the uterine corpus and cervix by 18 weeks, suggesting the maturation of smooth muscle cells may commence from 18 weeks of gestation. ESR-1 gene encodes estrogen receptor alpha, which plays a pivotal role in menstruation, pregnancy, and parturition. In adult female myometrium, estrogen performs functions in proliferation before term and contractile at term. Study design, size, duration This is an observational study. To investigate when exactly the smooth-muscle tissue appears during uterine development, we have collected 14 uterine tissue samples from 14 aborted fetuses across seven gestational time points from PCW 8 to PCW 15. Participants/materials, setting, methods Uterus from aborted fetuses from PCW8- PCW15 cover the fusion of Mullerian tube and development of Myometrium. The 10X genomics scRNA-seq and immune labeling were performed. In addition, we have integrated scRNA-seq data from adult uterine tissue for comparison. Main results and the role of chance We provide a single cell atlas of the human developing uterus, and we observed that smooth-muscle cells (SMCs), identified by ACTA2, TAGLN, MYH11, exhibited a significant increase in abundance starting from PCW 11, but weaker signals of SMCs were also detected at earlier stages. Using the iDISCO technique with continuous α-SMA labeling to examine the localization of α-SMA in the uterus between PCW10- PCW12, we observed the entire process of myometrial development in 3-D level. We utilized an oblique section of 3-D reconstruction uterus and extended it to 150 μm. Subsequently, apparent signals became visible in the middle of the uterine wall and the uterine fundus. Collectively, these findings suggest that the anatomical myometrium layer initially forms at PCW 11. We used the CytoTRACE to assess the capacity of differentiation of adult and fetal SMCs, SMCs come from fetus appeal a significant grander potential. Specifically, fetal uterine SMCs showed higher expression of ESR1, IGFBP5, and POSTN, while adult uterine SMCs exhibited higher expression of PDGFRB and IGFBP7. These results suggested ESR1+ SMCs could be the precursor of SMCs and SMCs in fetal uterus could be in a primary state. Limitations, reasons for caution While our study did not capture later stages of development or postnatal changes. Future studies are needed to understand the full spectrum of myometrial development. It is also important to note that the findings in this study are specific to human and may not directly translate to other species. Wider implications of the findings Our study provides a basis for studying abnormal myometrial development and its association with various reproductive disorders, such as the abnormal uterine development in female fetus with Turner syndrome. Potential biomarkers or therapeutic targets for uterine malformations and abnormal uterine contractility may also of research interest. Trial registration number not applicable

Effects of highly-textured and untextured polycrystalline layers on deformation mechanisms in amorphous submicron-layered materials

Amorphous alloys have high strength, but softening can lead to room temperature brittleness, limiting their applications. Typically, soft means low hardness and yield strength, and the lower the yield stress, the higher the fracture toughness. Two amorphous/crystalline multilayer samples with submicron single layer thickness were prepared. The crystalline layer of one sample is composed of highly-textured (111) nanocrystalline grains, and the other sample is untextured. Indentation experiments proved that the samples were plastically deformed, while the amorphous layer did not form shear bands with decreased layer thickness. The thickness reduction of the amorphous layer in the sample with highly-textured crystalline layers is greater than in the sample with untextured crystalline layers. The strain-hardening ability of the textured crystalline layer is higher, while the corresponding amorphous layer is deformed more severely with free volume annihilation and greater flow with more compact atoms. The amorphous layer corresponding to the untextured crystalline layer absorbs dislocations, and activates shear transformation zones (STZs), increasing the free volume near the interface. The annihilation of the free volume is less than the sample with highly-textured crystalline layers.

Baseline assessment of cervical cancer screening and treatment capacity in 25 counties in Kenya, 2022.

Cervical cancer is the leading cause of cancer deaths among women in Kenya. In the context of the Global strategy to accelerate the elimination of cervical cancer as a public health problem, Kenya is currently implementing screening and treatment scale-up. For effectively tracking the scale-up, a baseline assessment of cervical cancer screening and treatment service availability and readiness was conducted in 25 priority counties. We describe the findings of this assessment in the context of elimination efforts in Kenya. The survey was conducted from February 2021 to January 2022. All public hospitals in the target counties were included. We utilized healthcare workers trained in preparation for the scale-up as data collectors in each sub-county. Two electronic survey questionnaires (screening and treatment; and laboratory components) were used for data collection. All the health system building blocks were assessed. We used descriptive statistics to summarize the main service readiness indicators. Of 3,150 hospitals surveyed, 47.6% (1,499) offered cervical cancer screening only, while 5.3% (166) offered both screening and treatment for precancer lesions. Visual inspection with acetic acid (VIA) was used in 96.0% (1,599/1,665) of the hospitals as primary screening modality and HPV testing was available in 31 (1.0%) hospitals. Among the 166 hospitals offering treatment for precancerous lesions, 79.5% (132/166) used cryotherapy, 18.7% (31/166) performed thermal ablation and 25.3% (42/166) performed large loop excision of the transformation zone (LLETZ). Pathology services were offered in only 7.1% (17/238) of the hospitals expected to have the service (level 4 and above). Only 10.8% (2,955/27,363) of healthcare workers were trained in cervical cancer screening and treatment; of these, 71.0% (2,097/2,955) were offering the services. Less than half of the hospitals had cervical cancer screening and treatment commodities at time of survey. The main health system strength was presence of multiple screening points at hospitals, but frequent commodity stock-outs was a key weakness. Training, commodities, and diagnostic services are major gaps in the cervical cancer program in Kenya. To meet the 2030 elimination targets, the national and county governments should ensure adequate financing, training, and service integration, especially at primary care level.

Human Papilloma Virus-Independent/p53abnormal Keratinizing Squamous Cell Carcinoma of the Uterine Cervix Associated With Uterine Prolapse.

Knowledge about the morphologic and molecular characteristics of cervical squamous cell carcinomas (CSCCs) associated with uterine prolapse is very limited. Detailed histopathological and immunohistochemical (p16, p53, and cytokeratin 17), as well as molecular evaluation for human papillomavirus (HPV)-DNA and p53-mutational analyses in 4 consecutive CSCCs associated with uterine prolapse with definition of a hitherto not well-described HPV-independent/p53abnormal precursor lesion (HPV-independent cervical intraepithelial neoplasia [CIN; differentiated CIN]) and molecular tumorigenetic pathway. Cases diagnosed within 7 years with a mean age of 75 (range: 69-83) years and a mean tumor size of 7.3cm (range: 5.2-9.4cm). All patients presented with locally advanced disease, and 1 woman died of the disease within 4, and another within 14 months of follow-up. All CSCCs and their adjacent precursor lesions were negative for p16, with aberrant p53-expression and diffuse and strong staining for cytokeratin 17. Both the CSCCs and their precursors were negative for HPV-DNA but harbored a TP53 mutation. The precursor lesions were characterized by epithelial thickening with superficial keratinization, and the presence of basal and parabasal keratinocytes with mitotic figures beyond the basal layer, thus showing features similar to those seen in differentiated types of vulvar intraepithelial lesions (vulvar intraepithelial neoplasia [VIN] syn. HPV-independent/p53abn VIN), suggesting the terminology of differentiated CIN or HPV-independent/p53abn CIN. An HPV-independent pathogenetic pathway with a p53-alteration was identified for these cases. CSCC associated with uterine prolapse represents HPV-independent tumors harboring a TP53 mutation. For the first time, a precursor lesion of HPV-independent CSCC of the uterine cervix is described with a differentiated VIN-like morphology, and a separate tumorigenic pathway defined.

Accelerated Radiotherapy Alone Versus Chemoradiation in Locally Advanced Carcinoma Cervix: Long-Term Outcomes.

Introduction Chemoradiation (CRT) is the standard of care for the treatment of carcinomacervix, more benefits of CRT are seen in the early stageas compared to a locally advanced stage. Altered fractionation such as accelerated radiotherapy (ART) in locally advanced carcinoma cervix has not been explored much. Here, we have reported the long-term outcome of ART in comparison to conventional CRT in locally advanced cervical cancer patients. Methods From September 2011 to January 2014, 191 patients with locally advanced squamous cell carcinoma of the uterine cervix, FIGO stage IIB - IIIB were included in this study. They were randomized into two arms: the CRTarm (95 patients) versus the ART arm (96 patients). During external beam radiotherapy (EBRT), the patients in the CRT arm received conventional radiotherapy 50 Gy/25 fractions, 2 Gy/fraction, 5 fractions/week with cisplatin 40 mg/m2/week while patients in the ART arm received 50 Gy/25 fractions, 2 Gy/fraction, 6 fractions per week (Monday to Saturday) radiation alone. This was followed by three insertions of 6.5 Gy per fraction of high dose rate (HDR) brachytherapy at one-week intervals in both arms to keep the total treatment time 50 days in the CRT arm versus 45 days in the ART arm. Results The median follow-up of the study population was 57 months (range: 4-108 months). The patients with no residual disease (NRD) after EBRT and complete response (CR) at first follow-up were statistically less in the ART arm as compared to the CRT arm (30.2% versus 53.7% and 42.7% versus 63.2%; p = 0.006 and p = 0.024, respectively). However, there was no statistical difference in response at six months. High-grade acute toxicities hematological (9.5%) and gastrointestinal (15.8%) were more prevalent in the CRT arm in comparison to the ART arm, with no statistical significance (p>0.05) and Grade 1/2 genitourinary toxicity was significantly higher in the CRT arm. Late toxicities in both groups were equivalent. Recurrence, distant type of recurrence, and time to recurrence were similar in both groups. Five-year rates of overall survival (OS) and disease-free survival (DFS) were 51.2% versus 37.2% (p = 0.087) and 57.1% versus 46.3% (p = 0.223) in the CRT arm versus ART arm, respectively. Conclusion ART is a compelling alternative to concurrent chemoradiotherapy for locally advanced cervical cancer, particularly in patients with significant comorbidities, elderly women, and those in higher stages where concurrent chemotherapy's efficacy diminishes. It should be strongly considered when chemotherapy is contraindicated.

Prevalence of Human Papillomavirus Infection and its Association with the Risk of Cervical Cancer among Hiv-Positive Women in Plateau State, North-Central Nigeria

Study’s Novelty/Excerpt This study investigates the prevalence and risk factors of HPV among HIV-infected women in Plateau State, Nigeria, highlighting a significant correlation between low CD4+ counts, high viral loads, and increased HPV infection rates. By utilizing comprehensive diagnostic methods including ELISA for HPV detection and cytology for cervical abnormalities, the research offers robust data linking immunosuppression and HPV-related cervical pathology in a high-risk population. The findings emphasize the urgent need for targeted interventions to improve sexual health behaviors and further research on how low immunity accelerates cervical cancer progression in both HIV-positive women and the broader population. Full Abstract Human papillomavirus (HPV) is one of the most common sexually transmitted infections (STI) associated with cervical, uterine, and anogenital cancers. Persistent infection with HPV is associated with abnormal cervical cells, which can develop into cervical cancer if left untreated. Human papillomaviruses are the first viruses to have been acknowledged to prompt carcinogenesis, and they are linked with cancers of the uterine cervix, anogenital tumours, and head and neck malignancies. A hospital-based study of HIV-infected women across the three senatorial zones of Plateau State, Nigeria, was conducted between November 2018 to November 2020. Ethical approval for the study was first obtained from the ethical committee of Plateau State Specialist Hospital Jos, and informed consent to participate in the research was also obtained from each participant. HIV status confirmation was first done through standard rapid test procedures, followed by cytology testing via the Pap smear procedure to detect any precancerous or malignant changes in the cervix. Subsequent detection of HPV utilized the ELISA procedure, while CD4+ cell count and viral load estimations were done using flow cytometry and nucleic acid amplification techniques, respectively. Questionnaires were administered to obtain information on cervical cancer risk factors and clinical presentations. The overall prevalence of HPV was 28% among HIV-infected women. More HPV infection (31.9%) occurred in women with low CD4+ count (0-200 cells/mm3), and also highest (50.0%) among women with the highest HIV viral load (&gt;100 copies/mL). The possible risk factors identified in this study include multiple sexual partnering, low condom usage, and coinfection with other STIs, among others. In conclusion, this study identified a high HPV prevalence, low CD4+ counts, and coinfection with other STIs among high-risk populations (HIV-infected women). We, therefore, recommend improved sexual behaviours and further research on the impact of low immunity on the rate of progression of cervical abnormality to cervical cancer, not just in HIV-positive women but in the general population.