Uterine Cervical Carcinoma Research Articles

ZNF281 Facilitates the Invasion of Cervical Cancer Cell Both In Vivo and In Vitro †.

Background: Cervical cancer is the fourth most common cancer among women worldwide. The zinc finger transcription factor 281 (ZNF281)/ZBP-99 protein specifically binds to GC-rich DNA sequences and regulates gene expression, and it has been shown to promote tumor progression. In this study, we aim to investigate the function and molecular mechanism of ZNF281 in uterine cervical carcinoma. Methods: We conducted immunohistochemistry and Western blot assays to determine the expression of ZNF281 in eight human cervical cancer tissues. And, xenograft experiments involving the injection of HeLa cells into nude mice was used to determine the function of ZNF281 on proliferation. Transwell assays were used to detect the migration and invasion of HeLa cells after indicated that ZNF281 overexpression. Results: Our results indicated that ZNF281 protein levels were higher in cervical cancer tissues compared to normal cervical tissues. Additionally, ZNF281 was expressed in human cervical carcinoma cell lines, including HeLa, SiHa, C-33 A, CaSki, and HT-3, and is localized in both the cell nucleus and cytoplasm. ZNF281 overexpression did not influence HeLa cell proliferation or tumor size in situ. Moreover, nude mice injected with ZNF281-overexpressing cell lines developed more tumor lesions in the lungs compared to those injected with control cell lines. Conclusions: These findings suggest that ZNF281 is associated with tumor metastasis without affecting cell proliferation, both in vivo and in vitro.

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.

A rare instance of latent systematic error in volumetric-modulated arc therapy with field-extended multi-isocentre irradiation leading to a serious dose-delivery accident.

Volumetric-modulated arc therapy (VMAT) with field-extended multi-isocentre irradiation (VMAT-FEMII) is an effective irradiation technique, particularly for large planning target volumes in the craniocaudal direction. A variety of treatment planning techniques have been reported to reduce the dosimetric impact. However, there is no guarantee that unexpected latent systematic errors would not occur. Herein, we report the experience with a rare case that could have led to a serious VMAT-FEMII-related accident. A patient with uterine cervical carcinoma was scheduled for VMAT-FEMII to the whole pelvis and the para-aortic lymph node region. A combination of the two sets of field groups with different isocentres was planned: one to cover the para-aortic lymph nodes and the other to cover the whole pelvis. Measurements based on the pretreatment dose delivery quality assurance (QA) revealed an unexpected overdose of >20% in the field overlap region. This overdose phenomenon is not reflected in the calculated dose distribution in the radiotherapy treatment planning system. Therefore, the plan was altered; a homogeneous dose distribution inside the dose junction was achieved. Several analyses were performed to elucidate the overdosing phenomenon. However, no conclusive answer was found to why non-reflection at the calculated dose distribution was found. The limitations to VMAT-FEMII are primarily related to systematic errors in the positional setup from patient-derived and/or mechanical sources. However, this report highlights a rare case of overdosing caused by inverse optimization and dose calculation. We recommend checking the aperture status of the jaw and multi-leaf collimator at each control point of the treatment plan and using a high-resolution image measurement system on a VMAT-FEMII QA to confirm the dose junction status.

Assessment of malignant potential for HPV types 16, 52, and 58 in the uterine cervix within a Korean cohort

High-risk human papillomavirus (HR-HPV) is the primary carcinogen in uterine cervical carcinoma. While genotype-specific carcinogenic risks have been extensively studied in Western populations, data from Korean are sparse. This study evaluates the malignant potential of the three most prevalent HR-HPVs in Korea: HPV16, HPV52, and HPV58. We analyzed 230 patients who underwent cervical conization and had been tested for HPV within a year prior to the procedure, excluding those with multiple infections. This analysis was confined to patients with single HPV infections and assessed outcomes of CIN3+, which includes carcinoma in situ (CIN3) and invasive carcinoma. The incidence of invasive cervical cancer was 6.7% for HPV16, 1.7% for HPV52, and 2.0% for HPV58; however, these differences were not statistically significant (p = 0.187). The rate of CIN3+ for HPV16, HPV52, and HPV58 were 70.6%, 51.7%, and 58.8%, respectively. Despite the small sample size, which may limit the robustness of statistical analysis, the data suggest a higher observed risk with HPV16. These findings highlight the need for vigilant clinical management tailored to specific HPV genotypes and support the implementation of a nine-valent vaccine in Korea. Physicians should be aware of these genotype-specific risks when treating patients.

Evaluation of malignant potential based on infection with high-risk human papillomaviruses 16, 52, and 58 in the uterine cervix.

e17511 Background: The high-risk human papilloma virus (HR-HPV) has been known as the most important carcinogen in uterine cervical carcinoma. Generally, gynecologists recommend medical interventions for patients diagnosed with HSIL or higher. Previous studies have evaluated genotype-specific risk for carcinogenesis. However, the genotype-specific risk remains still unclear due to some limitations of those studies. This study aimed to evaluate the malignant potential of the three most prevalent HR-HPVs in Korea. Methods: Patients who underwent uterine cervical conization were included. They had received HPV test within a year before the surgery and those exhibiting concurrent multiple infections with HR-HPVs were excluded. Of single infections with HR-HPV, the three most prevalent HR-HPVs were included to analyze. To evaluate their malignant potential, CIS+, including carcinoma in situ (CIS) and invasive carcinoma, was categorized in each HR-HPV group. The ratios of pathologic diagnoses and odds ratios for malignant potential were evaluated between the three most prevalent HR-HPVs. Results: Totally 230 patients were found to have a single infection with HR-HPV16, HR-HPV52, or HR-HPV58. Of the included patients, 119 (51.7%), 60 (26.1%), and 51 (22.8%) were noted to be infected with HR-HPV genotypes 16, 52, and 58, respectively. CIS was diagnosed in 59 (49.6%), 27 (45.0%), and 25 (49.0%) patients in the HPV16, HPV52, and HPV58 single infection groups, respectively ( p = 0.839). Invasive carcinoma, regardless of histology such as squamous cell carcinoma or adenocarcinoma, was diagnosed in 8 (6.7%), 1 (1.7%), and 1 (2.0%) patient in the HPV16, HPV52, and HPV58 single infection groups, respectively ( p = 0.187). The CIS+ ratio was not significantly different among the HPV16, HPV52, and HPV58 single infection groups (67 [56.3%] vs. 28 [46.7%] vs. 26 [60.0%], [ p = 0.460]). Conclusions: Among the Korean women with single HR-HPV infection, HPV16, HPV52, and HPV58 were the three most common genotypes, in descending order. Although HPV16 was the most prevalent among the three, its malignant potential was not significantly different from those of HPV52 and HPV58 in the uterine cervix. This result supports the need for a nine-valent vaccine against HR-HPVs, covering HPV52, HPV58, and HPV16.

Role of the gel spacer in safely delivering whole pelvic radiation therapy without central shielding in computed tomography-based image-guided adaptive brachytherapy for uterine cervical cancer patients

BackgroundTo protect the rectum and bladder from high dose exposure, the Japanese guidelines for managing uterine cervical carcinoma recommend pelvic irradiation with central shielding (CS). Conversely, the European Society for Radiotherapy and Oncology (ESTRO) and the American Brachytherapy Society (ABS) guidelines recommend delivering ≥ 85 Gy to high-risk clinical target volume D90 (CTVHR D90%). In this study, we investigated whether a gel spacer can enable the safe delivery of the ESTRO/ABS-recommended doses to the target while observing dose constraints for the OARs without using CS in external beam radiation therapy (EBRT). Materials and MethodsTwenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between April 2017 and May 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy expressed in the form of the equivalent dose in 2 Gy fractions (EQD2) were calculated. Treatment outcomes and incidence of adverse events were also examined. ResultsThe median cumulative CTVHR D90%, rectum D2cm3, and bladder D2cm3 were 86.6 Gy (range, 69.8–103.7), 62.9 Gy (range, 55.3–72.5), and 72.0 Gy (range, 62.9–84.1), respectively. The median follow-up was 35.9 months (range, 10.9–70.3). The 2-year local control rate was 95% (95% CI: [69–99%]). There were no CTCAE ≥Grade 3 late gastrointestinal or genitourinary adverse events. ConclusionsThe use of gel spacer can enable ESTRO/ABS-recommended dose constraints even without using CS in EBRT, with favorable outcomes and low adverse event rates.

Baseline and early response 2-[18F]FDG-PET/MRI for prediction of radiotherapy outcome in uterine cervical squamous cell carcinoma: a prospective single-center observational cohort study

BackgroundShould early response imaging predict tumor response to therapy, personalized treatment adaptations could be feasible to improve outcome or reduce the risk of adverse events. This prospective single-center observational study on 2-fluorine-18-fluoro-deoxy-glucose (2-[18F]FDG) positron-emission tomography/magnetic resonance imaging (PET/MRI) features aims to investigate the association between semantic 2-[18F]FDG-PET/MRI imaging parameters and outcome prediction in uterine cervical squamous cell carcinoma (CSCC) treated with radiotherapy.ResultsEleven study participants with previously untreated CSCC were examined with 2-[18F]FDG-PET/MRI at baseline and approximately one week after start of curative radiotherapy. All study participants had at least 24 months clinical follow-up. Two patients relapsed during the follow-up period. Reduced tumor size according to visual assessment was present in 9/11 participants (median change in sum of largest diameters (SLD) − 10.4%; range − 2.5 to − 24.6%). The size reduction was less pronounced in the relapse group compared to the no relapse group, with median change in SLD − 4.9%, versus − 10.4%. None of the reductions qualified as significantly reduced or increased in size according to RECIST 1.1., hence all participants were at this stage classified as non-responders/stable disease. Median baseline functional tumor volume (FTV) for the relapse group was 126 cm3, while for the no relapse group 9.3 cm3. Median delta FTV in the relapse group was 50.7 cm3, representing an actual increase in metabolically active volume, while median delta FTV in the no relapse group was − 2.0 cm3. Median delta apparent diffusion coefficient (ADC) was lower in the relapse group versus the no relapse group (− 3.5 mm2/s vs. 71 mm2/s).ConclusionsEarly response assessment with 2-[18F]FDG-PET/MRI identified potentially predictive functional imaging biomarkers for prediction of radiotherapy outcome in CSCC, that could not be recognized with tumor measurements according to RECIST 1.1. These biomarkers (delta FTV and delta ADC) should be further evaluated.Trial registration Clinical Trials, NCT02379039. Registered 4 March 2015—Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/study/NCT02379039.

Do Concurrent Multiple Infections with High-Risk HPVs Carry a More Malignant Potential than a Single Infection in the Uterine Cervix?

The high-risk human papillomavirus (HR-HPV) has been known as the most important carcinogen in uterine cervical carcinoma. However, there is limited evidence of the malignant potential of these concurrent multiple infections. This study included women who had undergone cervical conization. They underwent an HPV test by cervical swab within 12 months before the surgery. They were divided into two groups: one with a single infection with HR-HPV16 and the other with concurrent multiple infections with HR-HPVs, including genotype 16. Pathologic examination classified cases as CIS+ to assess and compare the malignant potential in both groups, including carcinoma in situ (CIS) and invasive carcinoma. Of the 220 patients infected with HR-HPV16, the single infection group consisted of 120 patients (54.5%), whereas the concurrent multiple infections consisted of 100 (45.5%) patients. The rates of HSIL were significantly higher in the concurrent multiple infection group. However, the odds ratio for CIS+ did not show a significant difference between both groups (1.417, 95% CI = 0.831-2.414, p = 0.200). The malignant potential was not significantly different between concurrent multiple infections with HR-HPVs, including 16, and a single infection with 16 in Korean women.

Crosstalk between cell fate and survival pathways during uterine cervical carcinoma progression: a molecular and clinical perspective

The development of uterine cervical cancer is primarily attributed to infection by high-risk human papillomaviruses (HR-HPVs). E5, E6 and E7, the three early oncoproteins of HR-HPVs, have been implicated in initiation and progression of cervical cancer. The intricate molecular mechanisms that orchestrate aberrant cellular transformations to establish carcinoma of the cervical epithelium following viral infections are poorly understood. Here, we discuss how deregulation of three major cell fate regulatory pathways, Hedgehog, Wnt and Notch, and cell survival strategies involving EGFR signaling and G1/S checkpoint contribute towards cervical cancer development and progression. Further exploration of protein interaction database has revealed several genes that are involved in cervical cancer initiation and progression, and the two crucial "driver” genes, MYC and CTNNB1 (β-catenin), have been identified as major players in protein-protein interaction network. GSK3β emerged as the key mediator of crosstalk between Hedgehog, Wnt and Notch signaling pathways. GSK3β regulates cytoplasmic stabilization and nuclear translocation of β-catenin, which further impacts the expression of MYC, critical for cell cycle progression. Collectively, our analyses suggest that combinatorial therapeutic targeting of these proteins may be more effective in blocking cervical cancer initiation and progression.

Does infection of multiple HPV high-risk genotypes carry a higher malignant potential than a single genotype in uterine cervix? A retrospective study.

86 Background: The high-risk genotype of human papilloma virus (HPV) has been known as the most important carcinogen in uterine cervical carcinoma. It remains unclear that the infection with multiple high-risk genotypes carry a higher malignant potential risk compared with a single genotype in uterine cervix. Methods: This is a retrospective study of 695 patients underwent conization at Kyungpook National University Hospital in South Korea from 2012 to 2023. Participants were required to have undergone an HPV test by cervical swab within 12 months prior to the surgery. Patients with a negative result or a previous history of cancer were excluded. Additionally, patients older than 50 years were excluded to reduce bias. We included patients with the most common genotype in the cohort with only one high-risk genotype, and patients with multiple high-risk genotypes including the most common genotype. We categorized them based on pathologic results. Patients with HSIL, carcinoma in situ (CIS), invasive carcinoma were classified as ≥HSIL, while those with CIS, invasive carcinoma were classified as ≥CIS. The HPV test was performed using DNA microarray or real-time polymerase chain reaction, can detect 18 high-risk genotypes and 14 low-risk genotypes. The infection status of low-risk HPV and the vaccination for HPV were not considered in this study. The statistical analysis was conducted using SPSS (version 26). Results: A total of 146 patients younger than 50 years found to be infected with HPV high-risk genotype 16 or 16 with other high-risk genotypes. The HPV 16 single infection and multiple infection were found in 79 (54.1%), 67 (45.9%), respectively. Among patients with HPV 16 single infection, 61 (77.2%) were diagnosed with ≥HSIL and 45 (57.0%) were ≥CIS. In the HPV 16 multiple infection group, 56 (83.6%) were diagnosed with ≥HSIL and 34 (50.7%) were ≥CIS. There was no statistically significant correlation based on the HPV 16 single or multiple infection status for either ≥HSIL (HPV 16 single infection vs. multiple infection, odds ratio (OR)=0.666 [95% CI=0.289-1.531], p=0.407) or ≥CIS (HPV 16 single infection vs. multiple infection, OR=1.285 [95% CI=0.668-2.471], p=0.507). Conclusions: Among young women with only a single HPV high-risk genotype, the genotype 16 was the most common. Compared to the infection group with a single HPV high-risk 16 genotype, the malignant potential was not found to be significantly increased in the infection group with multiple HPV high-risk genotypes, including HPV genotype 16. [Table: see text]

A prognostic model using FIGO 2018 staging and MRI-derived tumor volume to predict long-term outcomes in patients with uterine cervical squamous cell carcinoma who received definitive radiotherapy

BackgroundUterine cervical carcinoma is a severe health threat worldwide, especially in China. The International Federation of Gynecology and Obstetrics (FIGO) has revised the staging system, emphasizing the strength of magnetic resonance imaging (MRI). We aimed to investigate long-term prognostic factors for FIGO 2018 stage II–IIIC2r uterine cervical squamous cell carcinoma following definitive radiotherapy and establish a prognostic model using MRI-derived tumor volume.MethodsPatients were restaged according to the FIGO 2018 staging system and randomly grouped into training and validation cohorts (7:3 ratio). Optimal cutoff values of squamous cell carcinoma antigen (SCC-Ag) and tumor volume derived from MRI were generated for the training cohort. A nomogram was constructed based on overall survival (OS) predictors, which were selected using univariate and multivariate analyses. The performance of the nomogram was validated and compared with the FIGO 2018 staging system. Risk stratification cutoff points were generated, and survival curves of low-risk and high-risk groups were compared.ResultsWe enrolled 396 patients (training set, 277; validation set, 119). The SCC-Ag and MRI-derived tumor volume cutoff values were 11.5 ng/mL and 28.85 cm3, respectively. A nomogram was established based on significant prognostic factors, including SCC-Ag, poor differentiation, tumor volume, chemotherapy, and FIGO 2018 stage. Decision curve analysis indicated that the net benefits of our model were higher. The high-risk group had significantly shorter OS than the low-risk group in both the training (p < 0.0001) and validation sets (p = 0.00055).ConclusionsOur nomogram predicted long-term outcomes of patients with FIGO 2018 stage II–IIIC2r uterine cervical squamous cell carcinoma. This tool can assist gynecologic oncologists and patients in treatment planning and prognosis.

Uterine Cervical Angioleiomyoma Mimicking Squamous Cell Carcinoma.

Angioleiomyoma, a rare variant of leiomyoma, is a benign tumor of mesenchymal origin. Angioleiomyomas of the female urogenital tract are extremely rare, with only six cases of uterine cervical angioleiomyoma previously reported in the literature. In this case study, we report on a 49-year-old female patient who presented with menorrhagia whose initial magnetic resonance imaging (MRI) findings suggested cervical squamous cell carcinoma (SCC). However, following the hysterectomy, histological examination confirmed the lesion to be angioleiomyoma. To the best of our knowledge, there have been no previously reported cases of angioleiomyomas presenting with MRI findings that are suggestive of uterine SCC. Recognizing that angioleiomyomas can mimic uterine malignancies on MRI may prove beneficial for future diagnostic and treatment strategies.

Implications of viral infections and oncogenesis in uterine cervical carcinoma etiology and pathogenesis.

Uterine Cervical Carcinoma (UCC) is the most prevalent gynecological malignancy globally, with a rising incidence in recent years. Accumulating evidence indicates that specific viral infections, including human papillomavirus (HPV), Epstein-Barr virus (EBV), Hepatitis B and C viruses (HBV and HCV), and human herpesvirus (HHV), may contribute to UCC development and progression. Understanding the complex interplay between viral infections and UCC risk is crucial for developing novel preventative and therapeutic interventions. This comprehensive review investigates the association between viral infections and UCC risk by examining the roles of various viral pathogens in UCC etiology and pathogenesis, and possible molecular mechanisms. Additionally, we evaluate current diagnostic methods and potential therapeutic strategies targeting viral infections for UCC prevention or treatment. The prevention of UCC has been significantly advanced by the emergence of self-sampling for HPV testing as a crucial tool, allowing for early detection and intervention. However, an essential challenge in UCC prevention lies in understanding how HPV and other viral coinfections, including EBV, HBV, HCV, HHV, HIV, or their concurrent presence, may potentially contribute to UCC development. The molecular mechanisms implicated in the association between viral infections and cervical cancer development include: (1) interference of viral oncogenes with cellular regulatory proteins, resulting in uncontrolled cell proliferation and malignant transformation; (2) inactivation of tumor suppressor genes by viral proteins; (3) evasion of host immune responses by viruses; (4) induction of a persistent inflammatory response, contributing to a tumor-promoting microenvironment; (5) epigenetic modifications that lead to aberrant gene expression; (6) stimulation of angiogenesis by viruses; and (7) activation of telomerase by viral proteins, leading to cellular immortalization. Additionally, viral coinfections can also enhance oncogenic potential through synergistic interactions between viral oncoproteins, employ immune evasion strategies, contribute to chronic inflammation, modulate host cellular signaling pathways, and induce epigenetic alterations, ultimately leading to cervical carcinogenesis. Recognizing the implications of viral oncogenes in UCC etiology and pathogenesis is vital for addressing the escalating burden of UCC. Developing innovative preventative and therapeutic interventions requires a thorough understanding of the intricate relationship between viral infections and UCC risk.

Dynamic contrast-enhanced MR imaging of uterine endometrial carcinoma with/without squamous differentiation.

Endometrial carcinoma with strong enhancement on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is suggestive of high-grade type II endometrial carcinoma. However, low-grade type I endometrial carcinoma may also sometimes show strong enhancement. We hypothesized that squamous differentiation would contribute to the strong enhancement at the early phase on DCE-MRI-like uterine cervical squamous cell carcinoma and compared the DCE-MRI findings of endometrial carcinoma with and without squamous differentiation. DCE-MRI of endometrial carcinoma including 41 low-grade type I endometrial carcinomas without squamous differentiation (LG), 39 low-grade type I endometrial carcinomas with squamous differentiation (LGSD), and 20 high-grade type II endometrial carcinomas (HG) was retrospectively evaluated. Significant difference in the time-intensity curves was found between LG and HG and LG and LGSD, whereas no significant difference was seen between HG and LGSD. Curve type 3 (initial signal rise which is steeper than that of the myometrium) was more frequent in HG (60%) and LGSD (77%) than in LG (34%). It should be recognized as a pitfall that high-grade type II endometrial carcinoma and low-grade type I endometrial carcinoma with squamous differentiation may show similar early strong enhancement on DCE-MRI.

CD8-positive Tumor-infiltrating Lymphocytes and Prognosis in Radiotherapy for Uterine Cervical Squamous Cell Carcinoma.

Prognostic factors, including CD8-positive tumor-infiltrating lymphocytes (CD8+TILs), in definitive radiotherapy (RT) for squamous cell carcinoma (SqCC) of the uterine cervix need to be studied. This study aimed to explore these factors in a retrospective cohort. Patients with SqCC who underwent definitive RT comprising external beam RT and intracavitary brachytherapy at our facility between April 2006 and November 2013 were evaluated. CD8 immunohistochemistry was performed in pre-treatment biopsy samples to analyze the prognostic significance of CD8+TILs in the tumor nest. Positive staining was defined as at least one CD8+ lymphocyte infiltrating the tumor area in the specimen. In total, 150 consecutive patients were included. Among them, 66 (43.7%) patients had International Federation of Gynecology and Obstetrics (FIGO, 2008 edition) stage IIIA or higher progressive disease. The median follow-up period was 61 months. In the entire cohort, the 5-year cumulative rates of overall survival (OS), progression-free survival (PFS), and pelvic recurrence-free rate (PRFR) were 75.6%, 69.6%, and 84.8%, respectively. Of the 150 patients, 120 (80.0%) patients were CD8+TIL positive. The independent favorable prognostic factors were FIGO stage I or II disease, administration of concurrent chemotherapy, and CD8+TILs for OS (p=0.028, 0.005, and 0.038, respectively); FIGO stage I or II disease and CD8+TILs for PFS (p=0.015 and <0.001, respectively); and CD8+TILs for PRFR (p=0.017). The presence of CD8+TILs in the tumor nest may be a favorable prognostic factor of survival after definitive RT in patients with SqCC of the uterine cervix.

Prevalence of High-Risk Human Papillomavirus Types and Their Association with Cervical Squamous Cell Carcinoma, and High- and Low-Grade Squamous Intraepithelial Lesions in Turkish Women.

This study aimed to investigate human papillomavirus (HPV) type prevalence in our region and the relationship between uterine cervical HPV types and squamous cell carcinoma (SCC)/intraepithelial lesions. HPV test results were obtained from patient file archives of the Gynecology and Obstetrics Clinic. Pathology report results were obtained from the digital records of the Pathology Laboratory and the patient file archives of the Gynecology and Obstetrics Clinic in 2018. The most frequently detected was HPV16 (29.2%), followed by HPV51 (13.1%), HPV56 (11%), HPV31 (9.2%), HPV52 (8.4%), and HPV68 (8.2%). HPV16 was positive in 50% of patients diagnosed with SCC, 54.9% of patients with HSIL, 27% of patients with LSIL, and 25% of cases diagnosed as benign (P<0.001). HPV18 was positive in 25% of patients diagnosed with SCC, 11% of patients with HSIL, 4.7% of patients with LSIL, and 5.2% of cases diagnosed as benign (P=0.019). The most frequent hrHPV genotype was HPV16, followed by HPV51, HPV 56, and HPV 31. There is an increase in the frequency of HPV51 and HPV56. HPV51, not included in HPV vaccines and is the second most frequent, should be included in these vaccines. In addition, although the frequency of HPV18 has decreased, HSIL and SCC generation is still high together with HPV16.

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Uterine Cervical and Endometrial Carcinomas: Histopathological Analysis of Survival and Local Control. A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study

A retrospective comparative analysis of the outcomes of gamma knife radiosurgery (GKRS) for brain metastases from uterine cervical carcinoma (CC) and endometrial carcinoma (EC), investigated the efficacy and prognostic factors for survival and local tumor control. Histopathological analysis was also performed. The authors retrospectively reviewed 61 patients with 260 tumors of CC and 73 patients with 302 tumors of EC who had undergone GKRS. The survival times after GKRS had no difference between CC and EC. Uncontrolled primary cancer was significant unfavorable factor. CC resulted in significantly higher neurological death and post-GKRS neurological deterioration. New lesions appeared intracranially after GKRS, with no significant difference between CC and EC. Local tumor control rates at 6, 12, and 24months after GKRS were 90.0%, 86.6%, and 78.0% for CC and 92.2%, 87.9%, and 86.4% for EC. Primary cancer of CC, more than 7cm3 volume, and prescription dose less than 20Gy were significantly correlated in control failure. Local tumor control rates were significantly lower for squamous cell carcinoma in CC. No significant differences were found between histopathological subtypes of EC. This study established a relationship between the efficacy of GKRS for CC and EC brain metastases and the histopathological. Though, survival time after GKRS has no difference between CC and EC, CC was significantly higher neurogenic death and neurological deterioration after GKRS. Squamous cell carcinoma had a significantly lower rate of local tumor control among all CC, thereby resulting in CC having lower local tumor control than EC.

Exploratory analysis of radiomic as prognostic biomarkers in 18F-FDG PET/CT scan in uterine cervical cancer.

To evaluate the performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) radiomic features to predict overall survival (OS) in patients with locally advanced uterine cervical carcinoma. Longitudinal and retrospective study that evaluated 50 patients with cervical epidermoid carcinoma (clinical stage IB2 to IVA according to FIGO). Segmentation of the 18F-FDG PET/CT tumors was performed using the LIFEx software, generating the radiomic features. We used the Mann-Whitney test to select radiomic features associated with the clinical outcome (death), excluding the features highly correlated with each other with Spearman correlation. Subsequently, ROC curves and a Kaplan-Meier analysis were performed. A p-value < 0.05 were considered significant. The median follow-up was 23.5 months and longer than 24 months in all surviving patients. Independent predictors for OS were found-SUVpeak with an AUC of 0.74, sensitivity of 77.8%, and specificity of 72.7% (p = 0.006); and the textural feature gray-level run-length matrix GLRLM_LRLGE, with AUC of 0.74, sensitivity of 72.2%, and specificity of 81.8% (p = 0.005). When we used the derived cut-off points from these ROC curves (12.76 for SUVpeak and 0.001 for GLRLM_LRLGE) in a Kaplan-Meier analysis, we can see two different groups (one with an overall survival probability of approximately 90% and the other with 30%). These biomarkers are independent of FIGO staging. By radiomic 18F-FDG PET/CT data analysis, SUVpeak and GLRLM_LRLGE textural feature presented the best performance to predict OS in patients with cervical cancer undergoing chemo-radiotherapy and brachytherapy.

S2882 Uterine Cervical Squamous Cell Carcinoma: A Rare Cause of Biliary Obstruction

Introduction: The incidence of biliary obstruction is 5 cases per 1000 people in the United States with reports of 21% caused by metastatic lesions to the pancreaticobiliary system. Metastatic lesion to the pancreas is rare, with few cases on uterine squamous cell cancer (SCC) metastasizing to the pancreas. We present a case report of a uterine cervical SCC with metastasis to the pancreas resulting in biliary obstruction. Case Description/Methods: A 51-year-old female with a history of stage 4b uterine cervical SCC previously treated with radiation and chemotherapy six years prior presented with elevated aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels two times the upper limit of normal and jaundice. Prior to presentation she was in remission. However, CT on presentation demonstrated new thickening of the midthoracic esophagus, with subcarinal lymphadenopathy and a 1.9 x 2.2 cm mass in the uncinate process of the pancreas causing biliary dilation. Follow-up PET imaging showed evidence of a new intense uptake in the pre-carinal space and new pancreatic head involvement (Figure 1a). She simultaneously underwent an Endoscopic Ultrasound (EUS) and Endoscopic retrograde cholangiopancreatography (ERCP) for stent placement (Figure 1b). EUS showed a 21 mm x 20 mm hypoechoic lesion at the pancreatic head/uncinate process (Figure c). A fine needle biopsy was performed. Pathologic evaluation was consistent with a metastatic lesion secondary to a keratinizing SCC subtype was identified. (Figure d). Discussion: Metastasis to the pancreas accounts for 2-5% of pancreatic malignancies. Majority of SCC are associated with cervical high risk-human papilloma virus (HPV) with HPV-16 and HPV-18 being responsible for the most common types of cervical cancers. To date there have been only two published reports in the literature on SCC of the uterine cervix metastasizing to the pancreas. This case report emphasizes the importance of differentiating primary pancreatic carcinomas from metastatic lesions to the pancreas from other primary sources. There are various imaging modalities for diagnosis such as PET, CT, MRI/MRCP, ultrasonography, and EUS. In our case we were able to identify a new mass in the pancreas with CT, MRI and PET imaging and diagnose it with EUS. The usage of EUS to achieve accurate histopathologic diagnosis is becoming more important to tailor specific management and treatment options for pancreatic tumorsFigure 1.: a: PET avid lesion; b: Stricture as seen on ERCP within the distal CBD; c: Pancreatic mass on EUS; d: pancreatic tissue involved by sheets of cells with round to oval and angulated nuclei, moderate amounts of dense eosinophilic cytoplasm, intercellular bridges, and focal keratin formation. Scattered mitoses, dyskeratotic keratinocytes and apoptotic debris

Immune-related 3-lncRNA signature with prognostic connotation in a multi-cancer setting

BackgroundAdvances in our understanding of the tumor microenvironment have radically changed the cancer field, highlighting the emerging need for biomarkers of an active, favorable tumor immune phenotype to aid treatment stratification and clinical prognostication. Numerous immune-related gene signatures have been defined; however, their prognostic value is often limited to one or few cancer types. Moreover, the area of non-coding RNA as biomarkers remains largely unexplored although their number and biological roles are rapidly expanding.MethodsWe developed a multi-step process to identify immune-related long non-coding RNA signatures with prognostic connotation in multiple TCGA solid cancer datasets.ResultsUsing the breast cancer dataset as a discovery cohort we found 2988 differentially expressed lncRNAs between immune favorable and unfavorable tumors, as defined by the immunologic constant of rejection (ICR) gene signature. Mapping of the lncRNAs to a coding-non-coding network identified 127 proxy protein-coding genes that are enriched in immune-related diseases and functions. Next, we defined two distinct 20-lncRNA prognostic signatures that show a stronger effect on overall survival than the ICR signature in multiple solid cancers. Furthermore, we found a 3 lncRNA signature that demonstrated prognostic significance across 5 solid cancer types with a stronger association with clinical outcome than ICR. Moreover, this 3 lncRNA signature showed additional prognostic significance in uterine corpus endometrial carcinoma and cervical squamous cell carcinoma and endocervical adenocarcinoma as compared to ICR.ConclusionWe identified an immune-related 3-lncRNA signature with prognostic connotation in multiple solid cancer types which performed equally well and in some cases better than the 20-gene ICR signature, indicating that it could be used as a minimal informative signature for clinical implementation.