Squamous Cell Cervical Cancer Research Articles

Cancer stem cell biomarkers SOX2 and Oct4 in cervical cancer patients undergoing chemoradiotherapy.

Cancer stem cell biomarkers SRY (sex-determining region Y)-box 2 (SOX2) and octamer-binding transcription factor 4 (Oct4) account for radioresistance in cervical squamous cell cancers (CSCCs). Their clinical implications are limited and contradictory. In this prospective cohort study, we recruited patients with FIGO IB2-IVA CSCC treated with primary chemoradiotherapy on regular follow-up. Tissue biopsy specimens were evaluated for SOX2 and Oct4 expression by immunohistochemistry, quantified by a product of proportion and intensity scores. A total of 59 patients were included. Most had a moderately differentiated (81%), keratinizing (59%) CSCC, and ≥FIGO stage IIB disease (95%). SOX2 expression (high:low 21:38 patients) and Oct4 expression (high:low 4:55 patients) had a significant interrelation (p=0.005, odds ratio (95% CI) - 1.23 (1.004-1.520)). At a median follow-up of 36 months, the 3-year overall survival (OS) was 60% and 53% for low and high SOX2 expression (p=0.856), and 54% and 100% for low and high Oct4 expression (p=0.114). The 3-year disease-frese survival (DFS) was 65% and 50% in the low and high SOX2 expression (p=0.259), and 59% and 75% for low and high Oct4 expression (p=0.598). SOX2 expression was the only variable significantly associated with a lower OS and DFS on regression analysis. Our study demonstrated a trend toward improved OS and DFS with low SOX2 and high Oct4 expression in CSCC patients undergoing chemoradiotherapy.

Metastasis of cervical cancer indicated by elevation of serum CA125 produced by mediastinal lymph nodes: a case report

BackgroundIn patient assessment for recurrence of neoplasia, a biomarker that shows an elevated serum value before the first treatment is a candidate for follow-up examination. The biomarker squamous cell carcinoma antigen is usually utilized for follow-up of squamous cell cancer of the cervix.Case presentationWe herein report a 30-year-old Japanese woman of postoperative metastasis of cervical squamous cell cancer to the mediastinal and supraclavicular lymph nodes as indicated by an elevated serum cancer antigen 125 concentration and not by the squamous cell carcinoma antigen value. After chemoradiotherapy and chemotherapy, the serum cancer antigen 125 concentration decreased to a normal value. Squamous cell carcinoma antigen was found to be distributed in both the squamous cell cancer tissue of the cervix and the supraclavicular lymph node metastatic tissue. By contrast, cancer antigen 125 was distributed in the supraclavicular lymph node metastatic tissue but not in the original squamous cell cancer tissue of the cervix.ConclusionIn this case, metastasis of cervical cancer to the mediastinal and supraclavicular lymph nodes was shown by the biomarker cancer antigen 125, which was not present in the original neoplasia.

Labeled-free quantitative proteomic analysis of cervical squamous cell carcinoma identifies potential protein biomarkers.

Cervical cancer remains a prevalent cancer among women, and reliance on surgical and radio-chemical therapies can irreversibly affect patients' life span and quality of life. Thus, early diagnosis and further exploration into the pathogenesis of cervical cancer are crucial. Mass spectrometry technology is widely applied in clinical practice and can be used to further investigate the protein alterations during the onset of cervical cancer. Employing labeled-free quantitative proteomics technology and bioinformatics tools, we analyzed and compared the differential protein expression profiles between normal cervical squamous cell tissues and cervical squamous cell cancer tissues. GEPIA is an online website for analyzing the RNA sequencing expression data of tumor and normal tissue data from the TCGA and the GTEx databases. This approach aided in identifying qualitative and quantitative changes in key proteins related to the progression of cervical cancer. Compared to normal samples, a total of 562 differentially expressed proteins were identified in cervical cancer samples, including 340 up-regulated and 222 down-regulated proteins. Gene ontology functional annotation, and KEGG pathway, and enrichment analysis revealed that the differentially expressed proteins mainly participated in metabolic pathways, spliceosomes, regulation of the actin cytoskeleton, and focal adhesion signaling pathways. Specifically, desmoplakin (DSP), protein phosphatase 1, regulatory (inhibitor) subunit 13 like (PPP1R13L) and ANXA8 may be involved in cervical tumorigenesis by inhibiting apoptotic signal transmission. Moreover, we used GEPIA database to validate the expression of DSP, PPP1R13L and ANXA8 in human cancers and normal cervix. In this study, we identified 562 differentially expressed proteins, and there were three proteins expressed higher in the cervical cancer tissues. The functions and signaling pathways of these differentially expressed proteins lay a theoretical foundation for elucidating the molecular mechanisms of cervical cancer.

Predictive factors of lymph node metastasis in patients with 2014 figo stage Ib1-IIa2 cervical squamous cell cancer: A multicentric study

Predictive factors of lymph node metastasis in patients with 2014 figo stage Ib1-IIa2 cervical squamous cell cancer: A multicentric study

Therapeutic pathomorphosis of stage IB–IIA cervical cancer cells after various regimens of preoperative HDR brachytherapy

Background. Despite of the constant improvement of existing treatment methods, involving the latest technologies into the treatment programs, the results of the treatment remain unsatisfactory. It is impossible to prevent the dissemination of tumor cells during surgery, which cause the tumor recurrence. Even in case of early stage cervical cancer, after only adequate conducted surgery, the relapse-rate is 20–30%, and the five-year survival rate is 40–60%. The aim of the work is to evaluate the effectiveness of different doses of preoperative HDR-brachytherapy in cervical cancer patients stage IB–IIA, based on the data of therapeutic pathomorphosis of the tumor. Materials and methods. There was investigated the structural and functional status of cells of squamous cell cervical cancer stage IB–IIA in two treatment schemes. According to the first scheme, there was conducted two sessions of brachytherapy with a single dose of 5 Gy with an interval of 7 days, up to the common dose of 10 Gy (5+5 Gy). According to another scheme, the single dose at the first session was 7 Gy, at the second session – 5 Gy, total dose was 12 Gy. The comparison group included primary patients with squamous cell cervical cancer and patients, who received fractional EBRT and EBRT + LDR-brachytherapy, total dose of 20 Gy and 40 Gy respectively. The morphofunctional status of cancer cells was investigated using standard electron microscopy methods. In all studied groups, there was detected the frequency of tumors samples, which contain large cells, the frequency of tumors with the presence of mitoses, and frequency of cases with significant therapeutic pathomorphosis. The obtained data was processed by the application of non-parametric statistical methods, using the «Biostat» software, and non-parametric criterion of the most plausible reliability assessment for small selections. Results. It is established that 26.9% of primary patients with cervical cancer had tumors with large cancer cells. After fractional irradiation with total doses of 20 and 40 Gy, an increase in the frequency of cases of tumors with such cells to 37.5 and 50.0%, respectively, was observed although these changes were unreliable in comparison with the control group of primary patients. However, after the first session of HDR-brachytherapy in a single dose of 5 or 7 Gy, in contrast to the indicators in the group of primary patients, there was a sharp and reliable increase in the frequency of tumors cases with large cancer cells up to 83.3% and 90%, respectively. At the same time, pronounced therapeutic pathomorphosis did not exceed 10.0–16.7% of cases. The second session of HDR brachytherapy at a dose of 5 Gy (total doses of 10 and 12 Gy) led both to a decrease in the frequency of tumors with large cancer cells to the level of control values (20 and 27.3%), and to a dose-dependent increase in the indicators of pronounced therapeutic pathomorphosis ( 40 and 70% respectively). Conclusions. There has been established that HDR-brachytherapy with the initial single dose of 5 or 7 Gy initiate a significant reaction, when the primary population of cancer cells is replaced by others, where prevail their large forms, which may be giant polyploid cancer cells. After the second session of brachytherapy of 5 Gy, the proportion of tumors, which are composed of large cells, significantly decreases simultaneously with the increase of significant therapeutic pathomorphosis in the cellpopulation of cervical cancer. The application of HDR-brachytherapy of 7 Gy at the first session will lead to the higher efficacy of the proposed scheme of the preoperative irradiation in cervical cancer patients stages IB–IIA, when the therapeutic pathomorphosis reaches 70%, when at the same time with a total dose of brachytherapy of 10 Gy, therapeutic pathomorphosis is only 40%.

Orbital Metastasis of Cervical Squamous Cell Cancer during Treatment with Pembrolizumab

Purpose: This case report presents a rare occurrence of squamous cell carcinoma metastasizing to the orbit from the cervix.Case summary: A 48-year-old female with cervical cancer and multiple bone metastases experienced binocular diplopia two days prior to admission to the Department of Gynecology for scheduled chemotherapy. She was undergoing treatment with pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, for metastatic cervical cancer. The patient exhibited unilateral ptosis and restricted eyeball movement in the right eye. Brain MRI revealed a well-defined lobulated lesion attached to the superior rectus muscle in the right orbit and orbital apex. In suspicion of metastasis, radiation therapy with a dosage of 3,600 cGy was administered to the right orbital area, resulting in a reduction in size of the metastatic lesion. However, distant metastases subsequently developed in the bone and soft tissue, leading to the patient's demise one month later.Conclusions: This report emphasizes the importance of considering orbital metastasis from cervical cancer in patients undergoing advanced stage chemotherapy. It highlights the rarity of such cases and underscores the need for heightened awareness of this malignancy in patients with underlying cancer.

Comparing the Diagnostic Performance of Quantitative PCR, Digital Droplet PCR, and Next-Generation Sequencing Liquid Biopsies for Human Papillomavirus–Associated Cancers

HPV-associated cancers, including oropharyngeal squamous cell carcinoma(HPV+OPSCC), cervical cancer(HPV+CC), and squamous cell carcinoma of the anus(HPV+SCCA), release circulating tumor HPV DNA(ctHPVDNA) into the blood. The diagnostic performance of ctHPVDNA detection depends on the approaches utilized and the individual assay metrics. A comparison of these approaches has not been systematically performed to inform expected performance, which in turn impacts clinical interpretation. A meta-analysis was performed using Ovid MEDLINE, Embase, and Web of Science Core Collection databases to assess the diagnostic accuracy of ctHPVDNA detection across cancer anatomic sites, detection platforms, and blood components. The population included HPV+OPSCC, HPV+CC, and HPV+SCCA patients with pre-treatment samples analyzed by quantitative PCR(qPCR), digital droplet PCR(ddPCR), or next generation sequencing(NGS). 36 studies involving 2,986 patients met the inclusion criteria. The sensitivity, specificity and quality of each study were assessed and pooled for each analysis.The sensitivity of ctHPVDNA detection was greatest with NGS, followed by ddPCR and lastly qPCR when pooling all studies, while specificity was similar(sensitivity: ddPCR>qPCR, p<0.001; NGS>ddPCR, p=0.014). ctHPVDNA from OPSCC was more easily detected compared to CC and SCCA, overall(p=0.044). In conclusion, detection platform, anatomic site of the cancer and blood component utilized impacts ctHPVDNA detection and must be considered when interpreting results. Plasma NGS-based testing should be considered the most sensitive approach for ctHPVDNA overall.

Do higher radiation doses improve survival for cervical esophageal squamous cell cancer patients treated with definitive chemoradiotherapy using intensity-modulated radiotherapy? A propensity-score matched analysis.

This study was conducted to determine whether higher doses of intensity-modulated radiotherapy (IMRT) could improve the survival rate in patients of cervical esophageal squamous cell carcinoma (CESCC), and lead to more severe treatment-related toxicity. The clinical records of stage I-IVA CESCC patients treated with definitive chemoradiotherapy (CRT) using IMRT between January 2013 and June 2018 were retrospectively analyzed. The patients in the high-dose (HD) group received ≥60 Gy and those in the standard-dose group received <60 Gy. A propensity score matching (PSM) was applied to balance the confounding factors between both groups. The primary endpoint was over-survival (OS). progression-free survival (PFS), loco-regional control (LRC), and treatment-related toxicity were also evaluated. A total of 136 patients with CESCC were included. Patients with N1-3 nodal and stages III-IVA of the disease (P < 0.05) were included in the HD group. The differences in the OS, PFS, and LRC between the two groups were not statistically significant (P = 0.350, 0.063, and 0.099, respectively). After PSM, significantly longer PFS and LRC were observed in the HD group. The difference in OS between the two groups was not statistically significant. There was no significant difference in the incidence of treatment-related toxicity between the two groups. The results of this PSM analysis suggested that higher doses may improve PFS and LRC for CESCC patients receiving CRT using OMRT, but do not demonstrate any statistically significant advantage in improving OS.

Correlation of immediate prevalence of cervical squamous cell precancers and cancers with HPV genotype and age in women with LSIL cytology: A retrospective analysis of 1617 cases.

To evaluate the immediate risk of cervical squamous cell precancers and cancers in women with low-grade squamous intraepithelial lesion (LSIL) cytology according to different high-risk human papillomavirus (hrHPV) results and age stratification. The study included 1617 women with LSIL cytology and underwent simultaneous Aptima HPV genotyping (E6/E7 mRNA test) followed by cervical biopsy. Among 1317 hrHPV positive cases, other 11 types of hrHPV were the most frequent (68.8%), followed by HPV16 (11.1%), HPV18/45 (4.1%), and HPV16/HPV18/45 (0.5%). Compared to other groups, HPV18/45 positive group and other 11 types of hrHPV group showed significantly higher prevalence of intraepithelial neoplasia grade (CIN)1 (p < .0001), while HPV16 positive and HPV16/HPV18/45 dual positive groups showed significantly higher prevalence of CIN2/3 (p < .0001). In addition, hrHPV positive, 25-39 years-old age group showed a significantly higher prevalence of CIN1 (p = .032) than the other age groups. Furthermore, CIN1 prevalence was significantly higher in patients under 40 or 50 years of age than in those over 40 or 50 years of age (p = .005 and p = .011, respectively). However, there was no significant difference among the different age groups in CIN2/3 prevalence in women with LSIL cytology. In southern Chinese women population, LSIL cytology carries very low immediate risk of high-grade squamous intraepithelial lesions (HSIL) (CIN2/3) in general. However, HPV16 positive and HPV16/HPV18/45 dual positive indicated a higher immediate risk of high-grade squamous intraepithelial lesions (HSIL) (CIN2/3). Age is not an immediate risk factor in this patient population for high-grade squamous lesions or SCC. These results are similar to data from cytology laboratories in the United States and other international settings, therefore strongly support the usage of ASCCP guidelines in this patient population.

Unclear tumor border in magnetic resonance imaging as a prognostic factor of squamous cell cervical cancer

Magnetic resonance imaging (MRI) is used for pretreatment staging in cervical cancer. In the present study, we used pretreatment images to categorize operative cases into two groups and evaluated their prognosis. A total of 53 cervical cancer patients with squamous cell carcinoma who underwent radical hysterectomy were included in this study. Based on MRI, the patients were classified into two groups, namely clear and unclear tumor border. For each patient, the following characteristics were evaluated: overall survival; recurrence-free survival; lymph node metastasis; lymphovascular space invasion; and pathological findings, including immunohistochemical analysis of vimentin. The clear and unclear tumor border groups included 40 and 13 patients, respectively. Compared with the clear tumor border group, the unclear tumor border group was associated with higher incidence rates of recurrence (3/40 vs. 3/13, respectively), lymphovascular space invasion (24/40 vs. 13/13, respectively), lymph node metastasis (6/40 vs. 10/13, respectively), and positivity for vimentin (18/40 vs. 10/13, respectively). Despite the absence of significant difference in recurrence-free survival (p = 0.0847), the unclear tumor border group had a significantly poorer overall survival versus the clear tumor border group (p = 0.0062). According to MRI findings, an unclear tumor border in patients with squamous cell cervical cancer is linked to poorer prognosis, lymph node metastasis, and distant recurrence of metastasis.

Poly(A)-specific ribonuclease protein promotes the proliferation, invasion and migration of esophageal cancer cells.

Bioinformatics analysis showed that the expression of the poly(A)-specific ribonuclease (PARN) gene in gastric cancer, head and neck squamous cell carcinoma, melanoma, cervical cancer and lung squamous cell carcinoma tissues was significantly higher than that in normal tissues and was associated with high stage and poor prognosis. The expression of the PARN gene in esophageal cancer (EC) tissue is also significantly higher than that in normal tissues, but the effect of PARN on the proliferation, migration and invasion of EC cells remains unclear. To investigate the relationship between PARN and the proliferation, migration and invasion of EC cells. The EC tissues of 91 patients after EC surgery and 63 paired precancerous healthy tissues were collected. PARN mRNA levels were measured using a tissue microarray, and the PARN expression level was evaluated using immunohistochemistry to analyze the relationship between PARN expression and clinicopathologic features as well as the survival and prognosis of patients. In addition, the effects of PARN gene knockout on tumor cell proliferation, invasion and migration were studied by using shRNA during the in vitro culture of EC cell lines Eca-109 and TE-1, and the effects of the PARN gene on tumor growth in vivo were verified by a xenotransplantation nude mice model. The expression of PARN in EC tissues was higher than that in adjacent normal tissues, and the level of PARN expression was significantly positively correlated with lymphatic metastasis. Patients with high PARN levels had poor overall survival. BIM, IGFBP-5 and p21 levels were significantly increased in the PARN knockout group, while the expression levels of the antiapoptotic proteins Survivin and sTNF-R1 were significantly decreased in the apoptotic antibody array data. In addition, the expression levels of Akt, p-Akt, PIK3CA and CCND1 in the downstream signaling pathway regulating EC progression were significantly decreased. The culture of EC cell lines confirmed that the apoptosis rate of EC cells was significantly increased, the growth and proliferation of tumor cells were significantly inhibited, and the invasion and migration ability of tumor cells were significantly decreased after PARN gene knockout. In vivo experiments of BALB/c nude mice transfected with Eca-109 cells expressing control shRNA (sh-NC) and PARN shRNA (sh-PARN) showed that the tumor volume and weight of nude mice treated with sh-PARN were significantly decreased compared with those of nude mice treated with sh-NC, indicating that PARN knockdown significantly inhibited tumor growth in vivo. PARN has antiapoptotic effects on EC cells and promotes their proliferation, invasion and migration, which is associated with the development of EC and poor patient prognosis. PARN may become a potential target for the diagnosis, prognosis prediction and treatment of EC.

A novel human papillomavirus and host DNA methylation score and detection of cervical adenocarcinoma.

The widespread introduction of Pap testing in the 1960s was followed by substantial reductions in the incidence of cervical squamous cell cancer (SCC). However, the incidence of cervical adenocarcinoma (ADC) did not decrease, likely because of low Pap test sensitivity for ADC and adenocarcinoma in situ (AIS). This study assessed a novel human papillomavirus (HPV) and host DNA Methylation Score for AIS and ADC screening. We measured methylation levels at CpG sites in the L2/L1 open reading frames of HPV16, HPV18, and HPV45-as well as 2 human loci, DCC and HS3ST2. Specifically, we tested exfoliated cervicovaginal cells from women in the HPV Persistence and Progression (PaP) cohort who were positive for 1 of HPV16, 18, or 45, including: 1) 176 withAIS/ADC, 2) 353 with cervical intraepithelial neoplasia-3 (CIN3) or SCC, and 3) controls who either cleared (HPV-Clearers; n = 579) or had persistent HPV16, 18, or 45 infection (HPV-Persisters; n = 292). CpG site-specific methylation percentages were measured using our reported next-generation methods. The Methylation Score was the average methylation percentage across all 35 CpG sites tested. Each individual CpG site had higher methylation percentages in exfoliated cervicovaginal cells collected from patients with AIS/ADC, and as well as those with CIN3/SCC, relative to either control group (weakest P = .004). The Methylation Score for AIS/ADC had a sensitivity of 74% and specificity of 89%. The multivariate odds ratio (OR) between the Methylation Score (4th vs 1st quartile) for AIS/ADC was ORq4-q1 = 49.01 (PBenjamini-Hochberg = 4.64E-12), using HPV-Clearers as controls. CIN3/SCC had similar, albeit weaker, associations with the Methylation Score. HPV16/18/45-infected women with Methylation Scores in the highest quartile had very high odds of AIS/ADC, suggesting they may warrant careful histologic evaluation of the cervical transition zone (eg, conization or loop electrosurgical excision procedure [LEEP]).

Single-Nucleus Transcriptome Profiling of Locally Advanced Cervical Squamous Cell Cancer Identifies Neural-Like Progenitor Program Associated with the Efficacy of Radiotherapy.

Radiotherapy is the first-line treatment for locally advanced cervical squamous cell cancer (CSCC). However, ≈50% of patients fail to respond to therapy and, in some cases, tumors progress after radical radiotherapy. Here, single-nucleus RNA-seq is performed to construct high-resolution molecular landscapes of various cell types in CSCC before and during radiotherapy, to better understand radiotherapy related molecular responses within tumor microenvironment. The results show that expression levels of a neural-like progenitor (NRP) program in tumor cells are significantly higher after radiotherapy and these are enriched in the tumors of nonresponding patients. The enrichment of the NRP program in malignant cells from the tumors of nonresponders in an independent cohort analyzed by bulk RNA-seq is validated. In addition, an analysis of The Cancer Genome Atlas dataset shows that NRP expression is associated with poor prognosis in CSCC patients. In vitro experiments on the CSCC cell line demonstrate that downregulation of neuregulin 1 (NRG1), a key gene from NRP program, is associated with decreased cell growth and increased sensitivity to radiation. Immunohistochemistry staining in cohort 3 validated key genes, NRG1 and immediate early response 3 from immunomodulatory program, as radiosensitivity regulators. The findings reveal that the expression of NRP in CSCC can be used to predict the efficacy of radiotherapy.

Concurrent intensity-modulated radiation therapy and chemotherapy plus nimotuzumab for locally advanced cervical squamous cell cancer: A long-term follow-up result

The study aimed to evaluate the safety and efficacy of concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy plus nimotuzumab for the treatment of locally advanced cervical squamous cell cancer (LACSCC). From December 2013 to March 2017, 34 patients with stages IB2&amp;ndash;IVA (FIGO 2009) cervical squamous cell cancer were enrolled and received concurrent chemoradiotherapy plus nimotuzumab. The prescription radiation dose was 50.4 Gy/28 F on the pelvic field with or without extended-field radiation. An additional 30&amp;ndash;36 Gy to Point A was delivered with high-dose-rate brachytherapy. Cisplatin 40 mg/m2 and nimotuzumab 200 mg were infused intravenously weekly. The main and secondary outcome measures were toxicity evaluated using common terminology criteria for adverse events 4.03. and the outcome evaluated using response evaluation criteria in solid tumors 1.1, respectively. The median follow-up duration was 66 months (13 &amp;ndash; 98 months). All patients received 6 times of IMRT, brachytherapy, and nimotuzumab. Among them, 24 received six cycles of chemotherapy, while 11 received 4&amp;ndash;5 cycles. No life-threatening toxicity was found. The incidence of acute Grade 3 bone marrow depression was 52.9% (18/34), and Grade 3 gastrointestinal tract reaction was 8.8% (3/34). The incidence of late toxicities was 58.8% (20/34), including vaginal-rectal fistula, intestinal obstruction, rectal hemorrhage, hematuria, vaginal stenosis, and paresthesia. About 90% of those were Grades 1&amp;ndash;2. Complete response was achieved in 33 cases (97.1%). The 3-year disease-free survival, local progression-free survival (LPFS), and overall survival rates were 79.4%, 91.2%, and 82.4%, respectively. The corresponding 5-year values were 79.4%, 91.2%, and 79.3%. In conclusion, concurrent IMRT and chemotherapy plus nimotuzumab may represent a well-tolerated and effective treatment regimen in patients with LACSCC.

Purple Urine Bag Syndrome in a Woman with Squamous Cell Cervical Cancer

Purple urine bag syndrome is a rare phenomenon whose striking presentation can lead to earlier recognition and treatment of a potentially serious medical condition. This is a unique condition of long11 term indwelling catheter associated urinary tract infection with distinct, purple-colored urine caused by bacterial metabolites. This infrequent occurrence was seen in a patient with stage IIIb squamous cervical cancer who presented to the emergency department with symptoms of a urinary tract infection in setting of indwelling bilateral percutaneous nephrostomy tubes. The patient’s physical exam was notable for left costovertebral tenderness, purple urine in bilateral nephrostomy bags and urine culture significant for proteus mirabalis. The patient was treated with intravenous antibiotics and fluid resuscitation. She unfortunately left against medical advice shortly after being admitted. She re presented to an outside hospital with fevers and non-draining nephrostomy tubes notable to have purulent discharge at the nephrostomy sites. The scant urine through the nephrostomy tubes was also noted to have a purple hue. She was found to have another urinary tract infection with Enterobacter cloacae and subsequently treated with intravenous antibiotics. During this admission, she underwent bilateral nephrostograms notable for significant clogging of tubes and bilateral ureteral patency. After the study, she underwent removal of the long-term indwelling catheters and was able to continue voiding spontaneously. She was discharged in good condition on a ten-day course of oral antibiotics. The occurrence of purple urine is highly associated with urinary tract infections. This process is thought to be caused by a metabolism of dietary tryptophan by intestinal bacteria to indole that is then absorbed into the circulation and then converted to indoxyl sulfate by hepatic enzymes. This substrate returns to circulation and is excreted in the urine where in the presence of bacteria with sulfatase and phosphatase activity converts indoxyl sulfate to indigo and indirubin resulting in the characteristic purple hue of the urine. Catheter associated urinary tract infections require antibiotic treatment and timely removal of catheter when appropriate to prevent complications including pyelonephritis and sepsis.

Expression of Vascular Endothelial Growth Factor-A (VEGF-A) in Adenocarcinoma and Squamous Cell Cervical Cancer and Its Impact on Disease Progression: Single Institution Experience.

Background and Objectives: The aim of this retrospective study was to determine the difference in VEGF-A expression in adenocarcinoma and squamous cell cervical cancer and to show the influence of VEGF-A expression on clinical, pathological, and therapeutic prognostic factors on the outcome of treatment and the survival of patients. Materials and Methods: The study included patients with cervical cancer who were treated in the period from 1 January 2010 to 31 December 2021 at the Clinic for Gynecology and Obstetrics, University Hospital Centre, Osijek. The researchers conducted a retrospective analysis of data from patients' medical history, along with the pathohistological findings and oncologist findings. The study included 66 patients with cervical cancer (divided into two subgroups of 33 with adenocarcinoma or squamous cell cervical cancer). Diagnosis was based on the pathohistological status and FIGO staging. VEGF-A expression was significantly higher in adenocarcinoma. Subjects with a higher expression of VEGF-A had a significantly higher rate of disease progression and a higher possibility for lethal outcome. Results: Statistically significant prognostic factors in bivariate analysis in predicting a negative treatment outcome were: older age, greater depth of stromal invasion, FIGO IIB stage, chemotherapy, and positive lymph nodes. In the multivariate analysis, age and positive lymph nodes were shown to be significant predictors for a negative treatment outcome. Conclusions: VEGF-A has shown to be statistically more expressed in adenocarcinoma, which correlates with disease progression, but not statistically significant in multivariate regression analysis as an independent prognostic factor for poor survival of the subjects.

The spectrum of homologous recombination deficiency in cervical cancer: Is it also a cervical issue?

5543 Background: Tumors deficient in homologous recombination DNA damage repair (HR-DDR) demonstrate sensitivity to therapeutic agents targeting the HR-DDR pathway, such as poly-ADP ribose phosphate (PARP) inhibitors. The landscape of homologous recombination deficiency (HRD) is not well-characterized for cervical cancer; thus, we sought to analyze the prevalence of somatic pathogenic gene variants (PGVs) in HRD genes in cervical cancers. Methods: The American Association for Cancer Research’s (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database version 13.0 was queried for all cervical cancer tumors via cBioPortal (http://genie.cbioportal.org). This is a publicly available, multi-institutional database of next-generation sequencing (NGS) genomic profiles of multiple tumors. PGV frequencies of 27 genes involved in HR-DDR were descriptively reported for cervical cancer tumors, with histologic stratification: ATM, ARID1A, ATRX, BRCA1, BRCA2, BARD1, BRIP1, BLM, BAP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, MRE11, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, WRN. Results: A total of 857 cervical tumors from 817 patients were included for analysis. At least one somatic PGV in an HRD gene was found in 16.5% of all tumors (141/857). When stratified by histological subtypes with at least 25 tumors sequenced, highest frequencies of ≥1 PGV in HRD genes were observed in mucinous cervical cancer (13/66, 19.7%), cervical adenocarcinoma (48/262, 18.3%), squamous cell cervical cancer (53/349, 15.2%), adenosquamous cervical cancer (6/43, 14.0%) and neuroendocrine cervical cancers (5/42, 11.9%). Substantial rates of PGVs in HRD genes were also observed in histological subtypes with fewer than 25 sequenced tumors. Across all tumors, HRD genes with the highest frequencies of PGVs were ARID1A (9%), BAP1 (3%), ATM (1.6%) and BRCA1 (1.6%). Conclusions: NGS data demonstrate a substantial rate of somatic PGVs in HRD genes in cervical cancers, including among HPV related subtypes. These data suggest the need to expand routine functional HRD status assessment to cervical cancers in order to further characterize the landscape of HRD in these tumors. Furthermore, genetically driven clinical trials are warranted to evaluate the efficacy of HRD-targeted therapies such as PARP inhibitors, ataxia telangiectasia, and Rad-3 related kinase (ATR) inhibitors. [Table: see text]

Phase II study combining an anti-core 1 O-glycans targeting humanized monoclonal antibody NEO-201 with pembrolizumab in adults with chemo-resistant solid tumors.

e14515 Background: NEO-201 is a humanized IgG1 mAb which binds to Core 1 and/or extended Core 1 O-glycans expressed by solid and hematological cancers. NEO-201 reacts against cancer tissues but not most normal tissues. NEO-201 can identify and kill immune suppressor cells (iSCs), such as regulatory T cells (Tregs), neutrophils, and granulocytic myeloid-derived suppressor cells (gMDSCs) in human PBMCs via antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). We observed a reduction in the percentage of circulating Tregs in subjects with stable disease (SD) following single-agent NEO-201 treatment in our Phase 1 study. Resistance to PD-1/PD-L1 blockade in solid cancers may be due to the activity of iSCs in the tumor microenvironment (TME). Based on this, we launched a Phase II study with a safety lead-in combining NEO-201 with pembrolizumab in adults who have progressed on prior checkpoint therapy. Methods: The recommended phase 2 dose (RP2D) of NEO-201 was determined to be 1.5 mg/kg IV every 2 weeks. Cohorts consisting of advanced non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), uterine or cervical cancer who progressed during or after one front-line standard of care treatment, including chemotherapy, checkpoint therapy and/or targeted therapy were eligible. Three patients received NEO-201 at the RP2D with pembrolizumab 400 mg IV every 6 weeks (1 cycle) and were evaluated for safety 2 weeks following the 1st cycle of the therapy. DLTs were defined as specific Grade 3 or 4 toxicities related to NEO-201. Results: Safety lead-in was successfully completed at RP2D with no DLTs. Four subjects were enrolled in the safety lead-in; one subject electively discontinued after the first infusion and was not evaluable for DLT. Of the 3 evaluable subjects, 1 subject with refractory cervical cancer remained on study with SD for 8.5 months, electively coming off study for surgical debulking. The other 2 subjects developed progressive disease. All subjects had grade 3-4 transient neutropenia, which was expected. Other common toxicities included grade 3-4 decreased white blood cells and lymphocytes, grade 3 anemia and grade 2 infusion reactions. Conclusions: NEO-201 has demonstrated the ability to bind and kill iSCs in vitro and this phenomenon was observed in the initial first in human clinical study. This Phase II study was designed to determine if NEO-201 can reactivate the effectiveness of checkpoint inhibitor therapy in subjects who previously progressed on check point therapy. The safety of combining NEO-201 with pembrolizumab has been successfully established and all 4 disease cohorts are now open to accrual with response rate as the primary endpoint. The maximum accrual on this study will be 126 patients. Clinical trial information: NCT03476681 .

COST ANALYSIS OF PATIENTS WITH SQUAMOUS CELL CERVICAL CANCER STAGE IIB-IIIB WITH PACLITAXEL CISPLATIN CHEMOTHERAPY FROM THE SOCIETAL PERSPECTIVE

Background: The high prevalence of cervical cancer patients and the variety of necessary expenses needed causing financial hardship to both the patient and hospital. Furthermore, the disparity between the INA-CBGs rates and the costs of treatment incurred by hospitals and the limited information regarding the costs of cervical cancer undergoing cisplatin paclitaxel chemotherapy as viewed from a societal perspective were the reasons to conduct this research. Objective: The aim of this study was to determine the cost of squamous cell cervical cancer patients at stage IIB-IIB who received cisplatin paclitaxel chemotherapy from a social perspective. So in this study the difference in costs is used to calculate costs from a hospital perspective. Methods: This research was an observational study with a prospective incidence approach and consecutive sampling as the sampling method. This research was conducted from January to June 2017 at Sanglah General Hospital, Denpasar. Cost data from a societal perspective for six chemotherapy series were obtained from the Claim Guarantee Installation, Fund Mobility Section, interviews and filling in the logbook by patients and then calculated using the micro-costing method. Results: The results of this study obtained five patients who met the inclusion criteria. From the perspective of BPJS Kesehatan, the average cost of cervical cancer with paclitaxel cisplatin chemotherapy was IDR 24.703.470,00. From a hospital perspective, the average cost of cervical cancer with paclitaxel cisplatin chemotherapy was IDR 6.619.204,00., and from the perspective of patients and their families, the average burden of costs for cervical cancer with paclitaxel cisplatin chemotherapy was IDR 9.149.300,00. Conclusion: Cost analysis on five squamous cell cervical cancer patients with stage IIB-IIIB with six series of paclitaxel cisplatin chemotherapy viewed from the perspective of BPJS Kesehatan, hospital was IDR 24,703,470.00, IDR 6,619,204.00, and IDR 9,149,300.00, respectively.&#x0D; Keywords: Cervical Cancer; Chemotherapy; Cost Analysis; Paclitaxel Cisplatin; Societal Perspective

Skin metastasis in squamous cell cancer of cervix: A case report

AbstractCervical cancer, the fourth most common cancer among females in the world, ranks the second in China. In advanced disease, metastases may be commonly present in the lungs, bones, liver and lymph nodes or elsewhere, but uncommon to the skin. In this report, a 63‐year‐old woman was diagnosed as stage IVB cervical squamous cell cancer in January 2021. The patient was scheduled for concurrent chemoradiotherapy; however, a metastatic lesion of skin was proved by biopsy during the process of treatment. She died 1 month after confirmed skin metastases. Cutaneous metastasis of cervical cancer may predict the mix of lymphatic and hematogenous metastasis and the rapid fatal termination.