Novel strategies in HPV­16­related cervical cancer treatment: An in vitro study of combined siRNA-E5 with oxaliplatin and ifosfamide chemotherapy.

BACKGROUND: Cervical cancer, primarily caused by HPV infection, remains a global health concern. Current treatments face challenges including drug resistance and toxicity. This study investigates combining E5-siRNA with chemotherapy drugs, Oxaliplatin and Ifosfamide, to enhance treatment efficacy in HPV-16 positive cervical cancer cells, targeting E5 oncoprotein to overcome limitations of existing therapies. METHODS: The CaSki cervical cancer cell line was transfected with E5-siRNA, and subsequently treated with Oxaliplatin/Ifosfamide. Quantitative real-time PCR was employed to assess the expression of related genes including p53, MMP2, Nanog, and Caspases. Cell apoptosis, cell cycle progression, and cell viability were evaluated using Annexin V/PI staining, DAPI staining, and MTT test, respectively. Furthermore, stemness ability was determined through a colony formation assay, and cell motility was assessed by wound healing assay. RESULTS: E5-siRNA transfection significantly reduced E5 mRNA expression in CaSki cells compared to the control group. The MTT assay revealed that monotherapy with E5-siRNA, Oxaliplatin, or Ifosfamide had moderate effects on cell viability. However, combination therapy showed synergistic effects, reducing the IC50 of Oxaliplatin from 11.42 × 10-8 M (45.36 µg/ml) to 6.71 × 10-8 M (26.66 µg/ml) and Ifosfamide from 12.52 × 10-5 M (32.7 µg/ml) to 8.206 × 10-5 M (21.43 µg/ml). Flow cytometry analysis demonstrated a significant increase in apoptosis for combination treatments, with apoptosis rates rising from 11.02 % (Oxaliplatin alone) and 16.98 % (Ifosfamide alone) to 24.8 % (Oxaliplatin + E5-siRNA) and 34.9 % (Ifosfamide + E5-siRNA). The sub-G1 cell population increased from 15.7 % (Oxaliplatin alone) and 18 % (Ifosfamide alone) to 21.9 % (Oxaliplatin + E5-siRNA) and 27.1 % (Ifosfamide + E5-siRNA), indicating cell cycle arrest. The colony formation assay revealed a substantial decrease in the number of colonies following combination treatment. qRT-PCR analysis showed decreased expression of stemness-related genes CD44 and Nanog, and migration-related genes MMP2 and CXCL8 in the combination groups. Apoptosis-related genes Casp-3, Casp-9, and pP53 showed increased expression following combination therapy, while BAX expression increased and BCL2 expression decreased relative to the control. CONCLUSION: The study demonstrates that combining E5-siRNA with Oxaliplatin or Ifosfamide enhances the efficacy of chemotherapy in HPV-16 positive cervical cancer cells. This synergistic approach effectively targets multiple aspects of cancer cell behavior, including proliferation, apoptosis, migration, and stemness. The findings suggest that this combination strategy could potentially allow for lower chemotherapy doses, thereby reducing toxicity while maintaining therapeutic efficacy. This research provides valuable insights into targeting HPV E5 as a complementary approach to existing therapies focused on E6 and E7 oncoproteins, opening new avenues for combination therapies in cervical cancer treatment.

Initial sarcopenia and body composition changes as prognostic factors in cervical cancer patients treated with concurrent chemoradiation: An artificial intelligence-based volumetric study.

OBJECTIVES: This study aimed to investigate the influence of baseline sarcopenia and changes in body composition on survival during cervical cancer treatment. METHODS: Patients diagnosed with stage IB1-IVB cervical cancer who underwent primary concurrent chemoradiation therapy (CCRT) between 2002 and 2022 were included. The exclusion criteria were prior radical hysterectomy, lack of pretreatment computed tomography (CT) imaging, or significant comorbidities. An artificial intelligence-based automatic segmentation program assessed body composition by analyzing CT images, defining L3 sarcopenia (L3 skeletal muscle index [SMI] <39cm2/m2) and volumetric sarcopenia (volumetric SMI <180.4 cm3/m3). Comparative and multivariate analyses identified the prognostic factors. The impact of body component changes during CCRT was explored. RESULTS: Among 347 patients, there were 125 recurrences and 59 deaths (median follow-up, 50.5 months). Seven patients were excluded from the volumetric sarcopenia analysis because of incomplete baseline CT data, and 175 patients were included in the analysis of body composition changes. Patients with L3 sarcopenia had a lower 5-year progression-free survival (PFS) rate (55.6% vs. 66.2%, p = 0.027), while those with volumetric sarcopenia showed a poorer 5-year overall survival rate (76.5% vs. 85.1%, p = 0.036). Patients with total fat loss during CCRT had a worse 5-year PFS rate than those with total fat gain (61.9% vs. 73.8%, p = 0.029). Multivariate analyses revealed that total fat loss (adjusted hazard ratio [aHR], 2.172; 95% confidence interval [CI], 1.066-4.424; p = 0.033) was a significant factor for recurrence, whereas L3 sarcopenia was not. Volumetric sarcopenia increased the risk of death by 1.75-fold (aHR, 1.750; 95% CI, 1.012-3.025; p = 0.045). CONCLUSIONS: Among patients with cervical cancer undergoing CCRT, initial volumetric sarcopenia and fat loss during treatment are survival risk factors. These findings suggest the potential importance of personalized supportive care, including tailored nutrition and exercise interventions.

Clinical Outcome Comparison between CT-Guided Versus all MRI-Guided Scenarios in Brachytherapy for Cervical Cancer: A Single-Institute Experience.

OBJECTIVES: Image-guided adaptive brachytherapy (IGABT) is the standard of care for patients with cervical cancer. The objective of this study was to compare the treatment outcomes and adverse effects of computed tomography (CT)-guided and magnetic resonance imaging (MRI)-guided scenarios. MATERIALS AND METHODS: Data of patients with cervical cancer treated using external beam radiotherapy followed by IGABT from 2012 to 2016 were retrospectively reviewed. CT-guided IGABT was compared with the three modes of MRI-guided IGABT: pre-brachytherapy (MRI Pre-BT) without applicator insertion for fusion, planning MRI with applicator in-place in at least 1 fraction (MRI ≥1Fx), and MRI in every fraction (MRI EveryFx). Patient characteristics, oncologic outcomes, and late radiation toxicity were analyzed using descriptive, survival, and correlation statistics. RESULTS: Overall, 354 patients were evaluated with a median follow-up of 60 months. The 5-year overall survival (OS) rates were 61.5%, 65.2%, 54.4%, and 63.7% with CT-guided, MRI PreBT, MRI ≥1Fx, and MRI EveryFx IGABT, respectively with no significant differences (p = 0.522). The 5-year local control (LC) rates were 92.1%, 87.8%, 80.7%, and 76.5% (p = 0.133), respectively, with a significant difference observed between the CT-guided and MRI ≥1Fx (p = 0.018). The grade 3-4 late gastrointestinal toxicity rates were 6% in the CT-guided, MRI ≥1Fx, and MRI EveryFx, and 8% in MRI PreBT. The grade 3-4 late genitourinary toxicity rates were 4% in the CT-guided, 2% in MRI PreBT, 1% in MRI ≥1Fx, and none in MRI EveryFx. No significant differences were observed in the oncologic and toxicity outcomes among MRI PreBT, MRI ≥1Fx, and MRI EveryFx. CONCLUSIONS: CT-guided IGABT yielded an acceptable 5-year OS, LC, and toxicity profile compared with all MRI scenarios and is a potentially feasible option in resource-limited settings.

The level of expression of HPV16 early transcripts is not associated with the natural history of cervical lesions.

The natural history of cervical cancer is closely linked to that of high-risk human papillomaviruses (HPV) infection. It is recognized that upon HPV DNA integration, partial or complete loss of the E2 open reading frame precludes expression of the corresponding protein, resulting in upregulation of the E6 and E7 viral oncoproteins. To better characterize HPV16 infection at the cervical level, viral load, viral DNA integration, and viral early transcript expression (E2, E5, and E6) were analyzed in a series of 158 cervical specimens representative of the full spectrum of cervical disease. Overall, the frequency of early transcript detection varied from 45% to 90% and tended to increase with lesion severity. In addition, the levels of E2, E5, and E6 transcript expression were slightly higher in high-grade lesions than in cervical specimens without abnormalities. Notably, early transcript expression was clearly associated with viral load, and no inverse correlation was found between the expression of E2 and E6 transcripts. No clear association was found between early transcript expression and HPV16 DNA integration, with the exception that samples with a fully integrated HPV16 genome did not harbor E2 or E5 transcripts. In conclusion, early HPV16 transcript expression appears to be associated with viral load rather than lesion grade. From a practical point of view, quantification of HPV16 early transcripts is difficult to translate into a relevant biomarker for cervical cancer screening.

Long-term outcomes of sentinel lymph node navigation surgery for early-stage cervical cancer.

BACKGROUND: Sentinel lymph node navigation surgery, which identifies the sentinel lymph node in early cervical cancers and omits systemic pelvic lymphadenectomy in cases where no lymph node metastasis is present, has recently gained attention. However, there are few reports on lymph node recurrence and the long-term outcomes of cervical cancer surgery performed using sentinel lymph node navigation surgery. In this study, we aimed to evaluate the long-term outcomes of sentinel node navigation surgery for early-stage cervical cancer. METHODS: One hundred thirty-eight patients with cervical cancer were enrolled. Sentinel lymph nodes were identified by injecting 99 m Technetium-labeled phytate and indocyanine green into the uterine cervix. Surgery and survival outcomes were also analyzed. RESULTS: The median age and body mass index of the patients were 40 years (20-78) and 21.7 kg/m2 (16.5-50.4), respectively. Open surgery, laparoscopic surgery, and robotic surgery were performed in 77 (56%), 53 (38%), and 8 (6%) patients, respectively. The overall and bilateral detection rates of the sentinel lymph node were 100% and 94%, respectively. Only one case (0.7%) exhibited lower extremity lymphedema, and pelvic lymphocele was observed in three cases (2.2%). Four cases (3%) experienced recurrence over a median follow-up of 57.5 months (range, 2-115 months), with five-year recurrence-free and overall survival rates of 97% and 97.3%, respectively. CONCLUSIONS: Our results demonstrate that sentinel node navigation surgery may be safe and effective for early-stage cervical cancer.

Salvage hysterectomy for persistent residual cervical cancer: assessment of prognostic factors.

In this multicenter retrospective cohort study of 99 patients who underwent salvage hysterectomy for residual disease in the uterine cervix following the completion of definitive radiotherapy for cervical cancer across 25 Japan Clinical Oncology Group-affiliated centers from 2005-2014, (i) time duration from the completion of definitive radiotherapy to the diagnosis of residual disease in the uterine cervix, (ii) salvage hysterectomy surgical margin status, and (iii) extent of residual disease, were independently associated with progression-free survival (PFS). Specifically, (i) time duration to identify residual disease of >62 days was associated with decreased PFS compared to ≤62 days (4-year rates 21.8% vs. 55.0%, adjusted-hazard ratio [aHR]=2.69, 95% confidence interval [CI]=1.55-4.67); (ii) presence of tumor in the surgical margin of hysterectomy specimen was associated with 4 times increased risk of disease progression compared to tumor-free surgical margin (4-year PFS rates 0% vs. 45.3%, aHR=4.27, 95% CI=2.20-8.29); and (iii) hazards of disease progression was 4.5-fold increased when the residual disease extended beyond the uterine cervix compared to residual disease within the uterine cervix only (4-year PFS rates 11.1% vs. 50.6%, aHR=4.54, 95% CI=2.60-7.95). In the absence of these 3 prognostic factors, 4-year PFS rate reached nearly 80% (78.6%, SAL-HYS criteria). In sum, these data suggested that early detection of persistent, residual disease following definitive radiotherapy for cervical cancer may be the key to improve survival if salvage hysterectomy is considered as a tailored treatment option. Ideal surgical candidate would be uterine cervix-contained disease and assurance of adequate tumor-free surgical margin.

Mid-treatment MRI-based tumor response assessment for tumor recurrence and patient survival in locally advanced adenocarcinoma of the cervix: A retrospective multicenter study of KROG 23-03.

OBJECTIVE: To evaluate the significance of response assessment with magnetic resonance imaging (MRI) during chemoradiotherapy (CRT) for outcomes of adenocarcinoma of the cervix. METHODS: A retrospective analysis of 102 patients diagnosed with FIGO 1B3-IVa cervical adenocarcinoma was conducted. Patients underwent definitive CRT and brachytherapy. Mid-treatment MRI-assessments were used to evaluate tumor response during radiotherapy, focusing on tumor volume reduction rate (TVRR), which was defined as an optimal reduction rate from initial tumor volume for tumor progression. Locoregional recurrence (LRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS) rates according to the tumor response were analyzed. RESULTS: Forty-five (44.1 %) of 102 patients experienced tumor downstaging during CRT, with 72 (70.5 %) demonstrating a complete response on post-treatment MRI three months after radiotherapy. With a median follow-up of 35.5 months, the 3-year PFS and overall OS rates for all patients were 60.0 % and 84.0 %, respectively. LRR and DM rates at 3 years were 25.2 % and 23.3 %, respectively. Patients with TVRR≥81.8 % had significantly longer 3-year PFS (75.4 % vs. 36.2 %, P < 0.001) and OS (93.2 % vs. 69.0 %, P = 0.002) rates than the other patients with TVRR<81.8 %. LRR (10.6 % vs. 45.6 %, P = 0.003) and DM (14.6 % vs. 33.5 %, P = 0.008) rates at 3 years were significantly lower in TVRR≥81.8 % group compared to TVRR<81.8 % group. In the multivariate analysis, positive initial lymph node (hazard ratio [HR], 2.11; confidence interval [CI], 1.25-3.87; P = 0.02] and TVRR (HR, 0.42; CI, 0.19-0.93; P = 0.03) were significantly associated with PFS. CONCLUSION: Mid-treatment MRI assessment is crucial and higher rates of tumor volume reduction during radiotherapy indicates better prognosis for tumor recurrence and patient survival in cervical adenocarcinoma.

Surgical treatment of recurrent gynecological malignancies.

OBJECTIVE: A comprehensive overview of surgical treatment of recurrent gynecological malignancies. Recurrent breast malignancies are not included in this review. METHODOLOGY: A review providing overview of surgical treatment options for recurrent malignancies of adnexa of the uterus (ovary, fallopian tube), uterine corpus, uterine cervix, and carcinoma of the vagina and vulva. CONCLUSION: Optimal surgical treatment for patients with recurrent cancer is based on multidisciplinary approach with stratification according to individual prognostic markers. These include patient's performance status, outcome of primary surgery, current extent of recurrence, and histopathological, molecular, and biochemical characteristics. Decision about choice of treatment should be individually discussed and evaluated by the multidisciplinary oncogynecological commission board.

Trojan-horse inspired nanoblaster: X-ray triggered spot attack on radio-resistant cancer through radiodynamic therapy.

Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.

Human papillomavirus vaccination and Pap test uptake, awareness, and barriers among young adults in Gulf Cooperation Council countries: A comparative cross-sectional survey.

BACKGROUND: Human papillomavirus (HPV) vaccination and Pap tests are recognized as effective preventive measures to reduce the incidence of HPV-related diseases among young adults. The objective of this study was to assess HPV vaccination and Pap test uptake, awareness, and barriers among young adults in the Gulf Cooperation Council (GCC) countries, including Bahrain, Kuwait, Oman, Qatar, the Kingdom of Saudi Arabia (KSA), and the United Arab Emirates (UAE). METHODS: A comparative cross-sectional study was conducted from January to April 2024, involving 831 young adults aged 18-39 residing in GCC countries. The main outcome measures were HPV vaccination and Pap test uptake rates, awareness of the HPV vaccine and Pap testing, and barriers to vaccination. Data were collected using online platforms. The Chi-square test and Fisher's exact test were used for data analysis. RESULTS: The UAE had the highest vaccination rate at 18.9% (50/264), followed by Qatar at 5.8% (6/104), and KSA at 4.6% (10/216), p < 0.001. Individuals with health insurance had higher vaccination rates than those without (11% vs. 5.4%, p = 0.006). Awareness of the HPV vaccine was highest in the UAE (49.6%) and KSA (58.8%), while awareness of Pap smear testing among females was similarly high in these countries (62.4% and 65.9%, respectively). However, actual Pap smear testing rates were highest in Bahrain (15.9%) and Qatar (13.4%). The main barriers to vaccination cited by participants were lack of knowledge (53.6%) and the absence of medical recommendations (13.2%). CONCLUSION: The study's findings suggest the need of targeted educational campaigns to increase HPV vaccine uptake among both genders and Pap test participation among females. Additionally, incorporating HPV screening and vaccination into routine national programs in GCC countries and emphasising the crucial role of healthcare providers in influencing vaccination decisions are recommended strategies.

Hispanic individuals' cervical cancer screening disparities amidst the COVID-19 pandemic.

OBJECTIVE: To examine the impact of the COVID-19 pandemic on cervical cancer screening rates of Hispanic individuals compared to non-Hispanic White (NHW) individuals in the United States, whether a responsive surge in catch-up screenings occurred as society adapted to pandemic changes, and to investigate the sociodemographic characteristics between the study populations. METHODS: Using cross-sectional data from the All of Us Research Program, which incorporates electronic health record data and survey data from a demographically, geographically, and medically diverse participant group, we assessed the annual cervical cancer screening rates during 2019-2021 by race/ethnicity among eligible individuals ages 21-64. RESULTS: Among 116,052 unique individuals (78,829 NHW and 37,223 Hispanic), Hispanic individuals had lower annual cervical cancer screening rates than NHWI across the three years studied. They experienced a more significant decrease in screening from 2019 to 2020 (39.27 %) compared to NHWIs (21.15 %) and less of a rebound increase in the following year, 2021 (10.33 % vs 13.83 %). Hispanic individuals aged 50-64 experienced the sharpest decline in screening rates (-43.01 % from 2019 to 2020). Hispanic individuals also experienced greater adverse social conditions, including lack of insurance or employment, lower educational attainment, and lower household income. CONCLUSIONS: Hispanic individuals experienced a more significant decrease in cervical cancer screening rates with the onset of the COVID-19 pandemic compared with NHW individuals and did not experience a robust rebound in cervical cancer screening rates in 2021. As a result, the disparity in cervical cancer screening rates between NHW and Hispanic individuals considerably worsened with the COVID-19 pandemic.

3D-printed individual template brachytherapy for the treatment of intractable central pelvic recurrent cervical cancer: A single institution experience.

OBJECTIVE: The prognosis of recurrent cervical cancer tends to be poor and there are limited effective treatments currently available for these patients. This study was developed to find a safe and effective treatment for patients with central pelvic recurrent cervical cancer. MATERIALS AND METHODS: This retrospective study analyzed patients with central pelvic recurrent cervical cancer who received 3D-printed individual template (3D-PIT) brachytherapy between February 2019 and June 2023. Analyses of dosimetric parameters, toxicity-related complications, and survival were conducted based on the data of these patients. RESULTS: Twenty-one patients with central pelvic recurrent cervical cancer patients were enrolled. All of them received 3D-printed individual template (3D-PIT) brachytherapy. The mean respective adjusted cumulative HRCTV-D90 and HRCTV-D98 values for these patients were 86.9 Gy and 75.4 Gy. And the local control (LC) rate of these patients was 57.1%. In these 21 patients, only 2 (9.5%) of them experienced grade 3-4 rectal adverse reactions, while 7 (33.3%) patients experienced grade 3-4 bladder adverse reactions. 5(23.8%) patients had fistula, while 3 of these 5 patients had undergone prior anti-VEGF targeted drug treatment which is a risk factor of fistula. The respective 2-year rates of overall and progression-free survival (OS and PFS) for these patients were 72.9% and 57.4%, with a 26-month median PFS. CONCLUSIONS: These single-institution data highlight the potential viability of 3D-PIT brachytherapy as an approach to managing intractable central pelvic recurrent cervical cancer following first-line treatment.

Diagnostic value for methylation in cervical cancer based on a small-molecule fluorescent probe targeting DNMT1.

BACKGROUND: Value analysis of a small-molecule fluorescent probe for methylation detection in different cervical lesions. MATERIALS AND METHODS: (1) The grayscale values of distinct lesion tissues were remarkably distinct among the four groups (p < 0.05). The comparison of the grayscale value between the two groups showed that the CA group noticeably exceeded the LSIL and cervicitis groups, and the HSIL group was apparently higher than the LSIL and cervicitis groups (p < 0.05); (2) The mean grayscale values of the enrolled subjects were calculated with 55.21 as the midline, with >55.21 as positive and ≤55.21 as negative. RESULTS: The results showed that the positive rate of the cervicitis group was 0.00%, the LSIL group 67.74%, the HSIL group 83.33%, and the CA group 100.00%. The results among the four groups were notably distinct (p < 0.05); (3) The comparison among DAPI, probe, bright, and merged images of cervicitis, LSIL, HSIL, and CA indicated that different cervical lesions were with quite various stains. CONCLUSION: The grayscale value, positive rate, and stained picture of distinct cervical lesions were remarkably different. The small-molecule fluorescent probe has a good value in differentiating cervical lesions and can be considered for popularization and application.

Cone-Beam Computed Tomography (CBCT)-Guided Adaptive Boost Radiotherapy for a Patient With Locally Advanced Cervical Cancer Ineligible for Brachytherapy.

Brachytherapy is a critical component of locally advanced cervical cancer treatment, and patients ineligible for brachytherapy historically have poor outcomes. Delivery of boost with stereotactic body radiation therapy (SBRT) has been studied, though toxicity is a concern. Recent case reports have explored adaptive radiation boost, which can adjust plans for inter-fraction motion using magnetic resonance guidance. Herein, we report the first patient with locally advanced cervical cancer ineligible for brachytherapy who was treated with a cone-beam computed tomography (CBCT)-guided adaptive boost following completion of chemoradiation. A 71-year-old female with locally advanced cervical cancer was treated with chemoradiation and was deemed ineligible for a brachytherapy boost due to tumor size, geometry, and a fistula with a tumor in the bladder. She was prescribed a boost to the primary tumor of 25 Gy in five fractions using CBCT-guided adaptive radiation following the completion of chemoradiation. A simulation was performed using a non-contrast CT fused with a mid-chemoradiation magnetic resonance imaging (MRI) scan to create an initial plan. For each treatment fraction, kilovoltage CBCTs were acquired, contours of organs at risk (OARs) were adjusted to reflect anatomy-of-the-day, and an adapted plan was generated. The initial and adapted plans were compared using dose-volume histogram objectives, and the adapted plan was used if it resolved OAR constraint violations or improved target coverage. The use of the initial treatment plan would have resulted in constraint violations for the rectum, sigmoid, and bladder in all fractions. The adapted plans achieved hard constraints in all fractions for all four critical OARs. The mean total treatment time across all five fractions was 58 minutes. This case demonstrates the feasibility of a CBCT-guided adaptive boost approach and the dosimetric benefits of plan adaptation in this setting. Though larger-scale and longer-term data are needed, CBCT-guided adaptive radiation may present a feasible alternative modality to deliver boost doses for brachytherapy-ineligible patients.

Exploring the Impact of COVID-19 on Cervical Cancer Screening Services: A Qualitative Study of Healthcare Providers' and Women's Perspectives and Experiences.

A qualitative exploration was conducted to analyse the reasons behind the low utilisation of cervical cancer screening services in Gwanda district, Zimbabwe, focusing on the impact of the COVID-19 pandemic. The study involved 5 focus group discussions with 36 women, utilising maximum variation sampling to explore the effects of COVID-19 on screening coverage. Additionally, in-depth interviews were conducted with 25 health-care providers from primary health facilities and the provincial hospital offering screening services. The results suggest a decline in the progress of the cervical cancer screening programme due to the disruptions caused by COVID-19 which subsequently reduced women's access to screening and treatment services. It was anticipated that restoring women's confidence in adherence to screening would require time post-pandemic. Moreover, findings highlighted the potential progression of undetected precursor lesions to advanced cancer stages during non-screening periods, which may increase future cervical cancer morbidity and mortality. The findings underscore the importance of integrating cervical cancer screening messaging within broader health communication strategies to emphasise the significance of health interventions for overall well-being. This study recommends the adoption of more efficient screening methods, such as Human-Papillomavirus self-sampling to mitigate future disruptions in screening services, thereby guiding policymakers towards implementing best screening approaches.

The value of contrast-enhanced ultrasound in cervical cancer assessed in comparison with magnetic resonance imaging.

Introduction: Currently, magnetic resonance imaging (MRI) is the most commonly used imaging method in the assessment of the loco-regional extension in cervical cancer. Contrast-enhanced ultrasound (abbreviated CEUS) is being investigated as an alternative or complement to the MRI investigation. Objectives: To evaluate the performance of CEUS in identifying loco-regional invasion of cervical cancer compared to MRI, considered the accepted reference standard. Methods: Sixty-one patients with histopathologically confirmed cervical cancer were investigated as part of the pre-treatment workup by CEUS and MRI. We calculated the accuracy and concordance of CEUS versus MRI for tumor invasion in the vagina, bladder, rectum, parametrium, and uterus. For the time-intensity curve associated parameters analyzed (TTPK, AUC, peak intensity, wash in and wash out gradient) we calculated sensitivity, specificity and threshold value of positivity, for tumor invasion at the above-mentioned sites, with graphical representation of the ROC (receiver operating characteristic) curve. Results: CEUS was highly accurate in detecting bladder (93.4%, 95% CI: 87.2-99.6) and uterine invasion (88.5%, 95% CI: 80.5-96.5). Substantial agreement between CEUS and MRI was observed for invasion in the uterine body (k=0.77, 95% CI: 0.56-0.98) and bladder (k=0.56, 95% CI: 0.35-0.77). ROC curve analysis for loco-regional invasions showed that the wash in gradient at a cut-off value of 2.23 had a sensitivity of 76% and a specificity of 67% in predicting uterine invasion. Conclusions: Our results demonstrate high accuracy and good agreement between CEUS and MRI regarding especially uterine and bladder invasion. This imaging method could help select patients in early stages for fertility sparing surgery, and also be of use in cases in which early bladder invasion is suspected.

Prognosis and treatment regimens for patients with different lymph node statuses in locally advanced cervical cancer.

OBJECTIVE: The survival outcomes of Stage IIIC1 in FIGO 2018 showed significant heterogeneity and it seems unreasonable to administer a uniform treatment regimen for Stage IIIC1 patients. This study aimed to assess the survival outcomes among patients with locally advanced cervical cancer based on various lymph node statuses, T-stage classifications, and treatment modalities. METHODS: This is a population-based cohort study utilizing the Surveillance, Epidemiology, and End Results Program from 2004 to 2018. Propensity score-based inverse probability of treatment weighting was used to achieve covariate balance. Women with locally advanced cervical cancer on different lymph node statuses who underwent radical hysterectomy + pelvic lymphadenectomy + chemoradiotherapy, chemoradiotherapy, or radiotherapy alone were examined. Trends, patient characteristics, and survival outcomes were compared across different treatment regimens. RESULTS: Among 8777 patients analyzed, patients with early T-stage and married were identified as independent protective factors for cancer-specific survival regardless of lymph node status. The survival outcomes ranked in descending order as follows: T1N0>T2N0>T1N1 = T2N1>T3N0>T3N1. Therefore, the FIGO Stage IIIC1 was re-stratified into IIC (T1N1+T2N1) and IIIC1(T3N1). Patients who underwent radical hysterectomy combined with adjuvant therapy exhibited superior 5-year cancer-specific survival rates compared to those treated with chemoradiotherapy among IB3, IIA2, and IIC. The therapeutic efficacy of chemoradiotherapy surpassed that of radiotherapy alone in IIIA, IIIB, IIIC1(T3N1), and IVA patients. CONCLUSION: Restratification of Stage IIIC1 based on T-stage effectively discerns patients with divergent prognoses. Radical surgery + chemoradiotherapy is significantly associated with improved survival in early T-stage, regardless of lymph node status in locally advanced cervical cancer.

Development and Validation of Radiomics-Based Models for Predicting the Parametrial Invasion in Stage IB1 to IIA2 Cervical Cancer.

Objective: To develop an early warning system that enables accurate parametrial invasion (PMI) risk prediction in cervical cancer patients with early-stage. Methods: We retrospectively collected 218 early-stage cervical cancer patients who were treated in Jingzhou Central Hospital from January 31, 2015, to January 31, 2023, and diagnosed with early stage cervical cancer by pathology. The prediction model training is achieved by randomly dividing 70% of the training queue population, with the remaining 30% used as the testing queue. Then, a prediction model based on machine learning algorithms (including random forest, generalized linear regression, decision tree, support vector machine, and artificial neural network) is constructed to predict the risk of PMI occurrence. Ultimately, the analysis of receiver operating characteristic curve (ROC) and decision curve analysis (DCA) is used to evaluate the predictive ability of various prediction models. Results: We finally included radiomics-based candidate variables that can be used for PMI model. Multivariate logistic regression analysis showed that energy, correlation, sum entropy (SUE), entropy, mean sum (MES), variance of differences (DIV), and inverse difference (IND) were independent risk factors for PMI occurrence. The predictive performance AUC of five types of machine learning ranges from 0.747 to 0.895 in the training set and can also reach a high accuracy of 0.905 in the testing set, indicating that the predictive model has ideal robustness. Conclusion: Our ML-based model incorporating GLCM parameters can predict PMI in cervical cancer patients with stage IB1 to IIA2, particularly the RFM, which could contribute to distinguishing PMI before surgery, especially in assisting decision-making on surgical scope.

Associations of clinical and modifiable behavioral risk factors with the histological progression of squamous intraepithelial lesions.

Cervical cancer is the third most common cancer in women worldwide. Human papillomavirus (HPV) has been established as a cause of invasive cervical cancer. However, HPV is predominantly transient and only a minority of cases persist and progress clinically. Certain epidemiological factors have been suggested to increase the risk of HPV persistence and progression. In the present study, 893 women were investigated, with an age range from 25 to 60 years old. PAP smears and colposcopy were used for assessment. Of these women, 108 were diagnosed with squamous intraepithelial lesions (SILs) and were further divided into high-grade SIL (HSIL) and low-grade SIL (LSIL). The dietary habits, sleep patterns and gynecological histories of these participants were studied, and it was found that the probability of having <3 meals a day [odds ratio (OR), 4.35; 95% confidence interval (CI), 1.73-10.95], having an unbalanced diet (OR, 3.90; 95% CI, 1.44-10.55), breakfast skipping (OR, 6.32; 95% CI, 2.40-16.61) and disrupted sleep (OR, 4.42; 95% CI, 1.79-10.93) was significantly higher in the HSIL group compared with the probability in the LSIL group. In addition, participants who had pregnancies prior to the age of 20 were 2.85 times more likely to have more advanced disease (OR, 2.85; 95% CI, 1.22-6.71). Cervical erosion was higher in the HSIL group compared with that in the LSIL group (OR, 3.31; 95% CI, 1.36-6.96). The present study highlights the protective effects of meal numbers, nutritious diet and sleep hygiene against HPV and the progression of SIL.