Nomograms for predicting prognostic value of combined neutrophil-to-lymphocyte ratio and SCC-Ag in locally advanced cervical cancer.

Background: Accumulating evidence supports the important role of inflammation in tumorigenesis and progression. Squamous cell carcinoma-associated antigen (SCC-Ag) is a tumor marker widely used to predict the prognosis of patients with cervical squamous cell carcinoma. This paper explored the predictive value of combined detection of neutrophil-to-lymphocyte ratio (NLR) to SCC-Ag for prognosis in patients with locally advanced cervical cancer (LACC). Methods: A retrospective analysis was conducted on 190 LACC patients who underwent concurrent chemoradiotherapy (CCRT) from January 2012 to December 2016. NLR and SCC-Ag were analyzed before treatment. Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal cutoff point for NLR and SCC-Ag. Kaplan-Meier analysis and Cox regression analysis were performed to assess their prognostic values. Nomograms were established to predict progression-free survival (PFS) and overall survival (OS), and the Harrell's concordance index (C-index) was introduced to evaluate the accuracy of predictions. Results: The optimal cutoff values for SCC-Ag and NLR were 3.25 ng/mL and 2.52, respectively. Patients with SCC-Ag >3.25 ng/mL and NLR >2.52 were significantly associated with decreased PFS and OS. Multivariate analysis indicated that SCC-Ag and NLR were independent prognostic factors for PFS (P=0.022 and P=0.004, respectively) and OS (P=0.031 and P=0.001, respectively). The area under the curve of SCC-Ag, NLR and their combination to predict PFS and OS of LACC were 0.688, 0.623, 0.708 and 0.684, 0.658, 0.723, respectively. C-index of nomograms based on PFS and OS were 0.725 [95% confidence interval (CI): 0.653-0.797] and 0.731 (95% CI: 0.658-0.804), respectively. Conclusions: The combination of SCC-Ag and NLR could provide a better predictive prognosis than SCC-Ag or NLR alone, and nomograms based on PFS and OS can be recommended as practical models for evaluating the prognosis of LACC patients.

Serum CYFRA21-1 and SCC-Ag levels in women during pregnancy and their diagnostic value for cervical cancer.

OBJECTIVES: The incidence of cervical cancer increases every year during pregnancy. Cervical cytology in pregnant women has a unique morphology and liquid-based cytology methods are prone to cause false positives. The aim of this study was to investigate the serum cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and squamous cell carcinoma associated antigen (SCC-Ag) concentrations in healthy pregnant women during pregnancy and to assess their diagnostic value for cervical cancer in pregnancy. METHODS: In this prospective study, 165 healthy non-pregnant women, 441 healthy pregnant women and 22 patients with cervical cancer in pregnancy were recruited. The healthy pregnant women group included 143 women in the first trimester (T1), 147 in the second (T2) and 151 in the third (T3). RESULTS: Both SCC-Ag and CYFRA21-1 levels were significantly different in the healthy pregnant women group compared to the control group. The CYFRA21-1 and SCC-Ag were higher in the T1 and T3 than in the control groups. However, there was no statistically significant difference in serum CYFRA21-1 and SCC-Ag levels in the T2 group compared to the control group. The AUCs of CYFRA21-1, SCC-Ag and CYFRA21-1 combined with SCC-Ag were 0.674, 0.792, and 0.805, respectively. The cut-off values of CYFRA21-1 and SCC-Ag were 6.64 ng/mL and 1.75 ng/mL, respectively. CONCLUSIONS: Serum CYFRA21-1 and SCC-Ag levels were higher in pregnant women during early and late pregnancy compared to non-pregnant individuals, while they were not statistically different from non-pregnant women during mid-trimester. CYFRA21-1 and SCC-Ag have diagnostic value for cervical cancer in pregnancy.

Study on the preoperative value of serum SCC-Ag in predicting the stromal invasion of cervical squamous cell carcinoma.

OBJECTIVE: To investigate the preoperative value of serum SCC-Ag in predicting the stromal invasion of cervical squamous cell carcinoma. METHODS: This study retrospectively analyzed 78 patients with early cervical squamous cell carcinoma who underwent surgery as initial treatment at the Senior Department of Obstetrics and Gynecology, the Seventh Medical Center of PLA General Hospital from January 2018 to September 2022 was implemented. The clinicopathological characteristics were statistically compared. The ROC curve was drawn to determine the optimal critical level of  preoperative serum SCC-Ag value for predicting cervical stromal invasion. RESULTS: The depth of myometrial invasion was not related to the age of diagnosis and HPV infection (p > 0.05), while it was related to tumor size, staging, tissue differentiation, LVSI, lymph node metastasis (LNM) and preoperative serum SCC-Ag value (p < 0.05).The area under the curve (AUC) of serum SCC-Ag value was 0.894 (p = 0.000, 95% CI 0.824-0.964), and preoperative serum SCC-Ag value 1.65 ng/ml was the best cutoff for predicting cervical stromal invasion in cervical squamous cell carcinoma. The sensitivity and specificity of diagnosis were 92.3% and 78.8%, respectively. CONCLUSION: If the preoperative serum SCC-Ag leval more than 1.65 ng/ml in patients with cervical squamous cell carcinoma, the risk of cervical stromal invasion will increase, which can provide a reference for clinical treatment.

Highly expressed circ_0000285 from serum and cervical exfoliated cells as a novel biomarker for the diagnosis of early stage-cervical cancer.

Circ_0000285 is reported to play an oncogenic role in the development of cervical cancer (CC). The aim of this research was to investigate the diagnostic power of circ_0000285 in CC. The expression of circ_0000285 in 116 healthy volunteers, 65 early-stage CC (ESCC) patients, and 87 locally advanced CC (LACC) patients was detected by qRT-PCR. The diagnostic values of circ_0000285 for CC and ESCC were evaluated by ROC curves analysis. The circ_0000285 expression was upregulated in serum and cervical exfoliated cells from preoperative CC patients compared to that of healthy volunteers. Increased circ_0000285 expression was found in preoperative LACC patients more than that in ESCC patients. The circ_0000285 expression was downregulated in serum from CC patients after surgery. The postoperative CC patients with high serum circ_0000285 expression was more prone to have a tumour relapse. High circ_0000285 expression was positively correlated with SCC-Ag level and HPV positive rate. The AUC of circ_0000285 for the diagnosis of CC and ESCC were 0.855 and 0.804, better than CA125 and SCC-Ag. When circ_0000285, CA125, SCC-Ag and HPV were combined, the AUC could reach 0.911 and 0.894. In summary, highly expressed circ_0000285 from serum and cervical exfoliated cells might be a promising diagnostic biomarker for ESCC.Impact statementWhat is already known on this subject? The CA125 and SCC-Ag have limitations in the diagnosis of ESCC. Recently, circRNAs have caused great attention and have been developing rapidly in clinical diagnosis of malignant tumours.What do the results of this study add? Highly expressed circ_0000285 from serum and cervical exfoliated cells might be used as a novel, non-invasive biomarker for the diagnosis of ESCC.What are the implications of these findings for clinical practice and/or further research? Circ_0000285 is superior to CA125 and SCC-Ag for the diagnosis of ESCC in clinical practice. The results help to supplement the shortcomings of traditional tumour markers and improve the diagnosis of ESCC.

SCC Antigen Concentrations in Fine-Needle Aspiration Samples to Detect Cervical Lymph Node Metastases: A Prospective Analysis.

OBJECTIVE: To determine the diagnostic value of measuring squamous cell carcinoma antigen (SCC-Ag) and cancer antigen 15-3 (CA15-3) concentrations in fine-needle aspiration (FNA) samples for the detection of squamous cell carcinoma (SCC) metastases in cervical lymph nodes. STUDY DESIGN: A prospective study with patients consecutively included between November 2018 and May 2021. SETTING: A tertiary head and neck oncologic center. METHODS: Out of 138 patients, SCC-Ag concentrations were analyzed in 168 FNA cervical lymph node samples and CA15-3 in 152 samples. Results were compared with FNA cytology (FNAC) or definitive histology to establish sensitivity and specificity rates. RESULTS: For the detection of cervical SCC lymph node metastases, SCC-Ag measurement had an 89.4% sensitivity and 79.3% specificity at a cutoff concentration of 0.1 µg/L. Measurement of CA15-3 concentration in addition to SCC-Ag concentration did not lead to improved accuracy for the detection of SCC. In histology-confirmed cases, FNAC had an 80.0% sensitivity and 100% specificity, as opposed to 93.3% and 57.1%, respectively, for SCC-Ag. CONCLUSION: Measurement of SCC-Ag concentration for detection of SCC lymph node metastases has a sensitivity at least comparable to FNAC and could be used as a relatively cheap screening tool in samples with nondiagnostic or indeterminate FNAC results or when multiple lymph nodes are sampled. However, SCC-Ag in FNA samples has a lower specificity than FNAC assessed by pathologists experienced in head and neck oncology. Addition of CA15-3 measurement did not lead to improved accuracy.

CXCL10 serves as a potential serum biomarker complementing SCC-Ag for diagnosing cervical squamous cell carcinoma.

BACKGROUND: Cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer which is the major cause of death in women worldwide. Although squamous cell carcinoma antigen (SCC-Ag) is widely used to detect CESC, it is not sensitive and specific enough to predict the disease. METHODS: We investigated serum CXC motif chemokine 10 (CXCL10) as potential diagnostic biomarker in detecting CESC in this study. Serum levels of CXCL10 and SCC-Ag were measured by ELISA or automated immunoassay in 345 participants, including 189 patients with different stages of CESC, 75 patients with cervical intraepithelial neoplasia, and 81 healthy individuals. Performances of CXCL10 and SCC-Ag as single biomarkers were analyzed by the ROC curves. The changes of serum levels of CXCL10 and SCC-Ag in 10 longitudinal followed-up CESC patients with partial response (PR) during chemoradiotherapy or chemotherapy were evaluated. RESULTS: The two markers showed similar diagnostic capacity in distinguishing both CESC early stage from healthy controls (AUCCXCL10 = 0.740, AUCSCC-Ag = 0.710) and all CESC from healthy controls (AUCCXCL10 = 0.775, AUCSCC-Ag =0.793). Moreover, CXCL10 showed ability in distinguishing cervical intraepithelial neoplasia from healthy control (AUCCXCL10 = 0.727) and cervical cancer SCC-Ag-negative from healthy control. (AUCCXCL10 = 0.739). The combination of CXCL10 and SCC-Ag displayed significant improvement of AUCs than individual SCC-Ag or CXCL10 in the analysis groups (healthy vs all cervical cancer, healthy vs cervical cancer early stage). The AUCs were improved to 0.877 (AUCSCC-Ag = 0.793, P < 0.05) to distinguish healthy controls from all CESC and 0.828(AUCSCC-Ag = 0.710, P < 0.05) to distinguish healthy controls from CESC early stage by the combination of the two markers, respectively. Significant differences of serum CXCL10 levels were found between CESC patients at late tumor stage and CESC patients at early tumor stage (P < 0.01). Serum CXCL10 levels of the CESC patients who had partial response after treatment significantly decreased during treatment (P = 0.013), whose consistent and inconsistent frequency with the response were the same as serum SCC-Ag levels. CONCLUSIONS: The results indicated that CXCL10 is a potential serum biomarker complementing SCC-Ag in prediction of CESC. CXCL10 showed ability in the diagnosis of SCC-Ag negative CESC and the combination of CXCL10 and SCC-Ag inhibited improved performance compared with SCC-Ag alone.

The prognostic significance of pretreatment squamous cell carcinoma antigen levels in cervical cancer patients treated by concurrent chemoradiation therapy and a comparison of dosimetric outcomes and clinical toxicities between tomotherapy and volumetric modulated arc therapy.

BACKGROUND: To analyze the prognostic factors associated with stage IB-IVA cervical cancer in patients who underwent concurrent chemoradiation therapy (CCRT) and to compare the clinical toxicities and dosimetric parameters of organs at risk between the different radiotherapy techniques. METHODS: This retrospective study enrolled 93 patients with stage IB-IVA cervical cancer who underwent definitive CCRT between April 2009 and December 2017. Nine patients (9.7%) received 3DCRT, 43 patients (46.2%) underwent VMAT, and 41 patients (44.1%) received tomotherapy, and all of them followed by brachytherapy using a 2D planning technique. The treatment outcomes and related prognostic factors were analyzed. We also compared the clinical toxicities and dosimetric parameters between the different techniques used for the last 30 patients. RESULTS: With a median follow-up of 52.0 months, the 5-year overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastases-free survival (DMFS) were analyzed. In a Cox proportional hazards regression model, pretreatment SCC Ag > 10 ng/mL was a significant prognostic factor for PFS (hazard ratio [HR] 2.20; 95% confidence interval [CI] 1.03-4.70; P = 0.041), LRRFS (HR, 3.48; 95% CI 1.07-11.26; P = 0.038), and DMFS (HR 2.80; 95% CI 1.02-7.67; P = 0.045). Increasing the rectal volume receiving a radiation dose exceeding 30 Gy (V30 of rectum; odds ratio [OR] 1.15; 95% CI 1.10-1.30; P = 0.03) was associated with a higher possibility of ≥ Grade 2 acute radiation therapy (RT)-related diarrhea. The median rectal V30 values were 56.4%, 97.5%, and 86.5% for tomotherapy, 3-dimensional conformal radiation therapy (3DCRT), and volumetric modulated arc therapy (VMAT), respectively (P < 0.001). In addition, the chance of experiencing ≥ Grade 2 acute diarrhea were 10.0%, 66.7%, and 54.5% for tomotherapy, 3DCRT, and VMAT, respectively (P = 0.029). CONCLUSIONS: Patients with pretreatment SCC Ag ≤ 10 ng/mL have better PFS, LRRFS, and DMFS than those with pretreatment SCC Ag > 10 ng/mL. The rectal V30 is a significant predictor of severe acute diarrhea. Tomotherapy significantly decreased the rectal V30, reducing the severity of acute RT-related diarrhea during external beam RT. Trial registration This study was approved by the institutional review board at Kaohsiung Medical University Hospital. The registration number is KMUHIRB-E(I)-20190054 and retrospectively registered on 2019/3.

Prognostic value of tumor measurement parameters and SCC-Ag changes in patients with locally-advanced cervical cancer.

OBJECTIVE: To investigate the prognostic relevance of specific measurement parameters such as tumor diameter, tumor volume, tumor volume reduction rate (TVRR), and changes in the squamous cell carcinoma antigen (SCC-Ag) level in patients with locally-advanced cervical cancer (LACC) undergoing concurrent radiotherapy and chemotherapy. METHODS: This was a retrospective study of 203 patients with stage IIA-IVA cervical squamous cell carcinoma who were newly diagnosed at our hospital between January 2011 and March 2015. Clinical data and pre-and post-treatment imaging information were collected and each parameter was calculated using 3DSlicer software. The pre/post-treatment tumor diameter (TDpre/post), tumor volume (TVpre/post), SCC-Ag (SCCpre/post), and TVRR, SCC-Ag reduction rate (SCCRR) were analyzed and their prognostic relevance evaluated. RESULTS: The median follow-up was 69 months. The 5-year overall survival (OS) and disease progression-free survival (PFS) rates were 69.5% and 64.5%, respectively. On univariate analysis, TDpre/post, TVpre/post, TVRR, SCCpre/post and SCCRR showed significant association with OS and PFS (P < 0.05). On multivariate analysis, TDpre [Hazard ratio (HR) = 0.373, P = 0.028], TDpost (HR = 0.376, P = 0.003) and SCCpost (HR = 0.374, P = 0.001) were independent predictors of OS. TVRR (HR = 2.998, P < 0.001), SCCpre (HR = 0.563, P = 0.041), and SCCpost (HR = 0.253, P < 0.001) were independent predictors of PFS. Tumor measurement parameters showed a positive correlation with SCC-Ag (P < 0.05). CONCLUSION: TDpre/post, TVpre/post, TVRR, SCCpre/post, and SCCRR were prognostic factors in LACC. TDpre/post and SCCpost showed the most significant prognostic value. TVRR and SCCpre/post were closely related to disease progression. Further studies should investigate the correlation between measurement parameters of tumor and SCC-Ag.

Squamous cell carcinoma antigen combined with HPV-16 infection in predicting high-grade squamous intraepithelial lesions of the cervix.

An early screening of HPV and the Thinprep Cytology Test (TCT) can effectively prevent cervical cancer. However, patients with high-grade cervical intraepithelial neoplasia usually escape current screening methods and commonly develop cervical cancer. Hence, to identify effective and specific screening methods for high-grade cervical intraepithelial neoplasia is of vital necessity. In this study, 541 patients collected in Sun Yat-Sen hospital from January 2007 to December 2016 were selected. HPV genotype detection and SCC-ag detection were done in these patients. It was found that when serum SCC-ag level exceeded over 0.39 ng/ml in HPV-16 positive patients, the sensitivity and specificity of this novel approach to predict high-grade cervical intraepithelial neoplasia could reach to 83.1% and 62.1%, respectively. The result suggested that the combination of serum SCC-ag level and HPV-16 infection could be used as a novel approach for high-grade cervical intraepithelial neoplasia screening.Impact statementWhat is already known on this subject? Patients with a high-grade cervical intraepithelial neoplasia usually escape current screening methods.What do the results of this study add? When serum SCC-ag level exceeded over 0.39 ng/ml in HPV-16 positive patients, the sensitivity and specificity to predict high-grade cervical intraepithelial neoplasia could reach to 83.1 and 62.1%, respectively.What are the implications of these findings for clinical practice and/or further research? Combination of serum SCC-ag level and HPV-16 infection could be used to screen high-grade cervical intraepithelial neoplasia.

Assessment of retroperitoneal lymph node status in locally advanced cervical cancer.

BACKGROUND: The assessment of retroperitoneal lymph node status in patients with locally advanced cervical cancer is still a problem. This study aimed to explore the choice of these assessment methods. METHODS: Laparoscopic retroperitoneal lymphadenectomy was performed in 96 patients with advanced cervical cancer. The positive rates of lymph node metastasis were analyzed. The values of computed tomography lymph node minimum axial diameter (MAD) and squamous cell carcinoma antigen (SCC-Ag), and their combination in predicting retroperitoneal lymph node metastasis were compared. High-risk factors for common iliac lymph node (CILN) and/or para-aortic lymph node (PALN) metastasis were analyzed. RESULTS: The lymph node metastasis rate was 62.50% and the CILN and/or PALN metastasis rate was 31.25%. Overall, 96 patients had 172 visible lymph nodes. The positive rate of lymph node metastasis was significantly higher in the MAD ≥1.0 cm group (83.33%) than in the 0.5 cm ≤ MAD < 1.0 cm group (26.82%). The critical values of MAD and SCC-Ag in determining lymph node metastasis were 1.0 cm and 5.2 ng/mL, respectively. The accuracy, specificity, and Youden index of MAD ≥1.0 cm combined with SCC-Ag ≥ 5.2 ng/mL for evaluating lymph node metastasis were 75.71%, 100%, and 0.59, respectively, and were significantly different from the values for the MAD ≥1.0 cm (72.09%, 80.56%, and 0.47, respectively) and SCC-Ag ≥ 5.2 ng/mL (71.43%, 68.97%, and 0.42, respectively) groups. Correlation analysis showed that non-squamous cell carcinoma, pelvic lymph node (PLN) MAD ≥1.0 cm plus number ≥ 2, and 1 PLN MAD ≥1.0 cm with CILN and/or PALN MAD 0.5-1.0 cm were risk factors for CILN and/or PALN metastasis. CONCLUSION: Patients with MAD ≥1.0 cm and SCC-Ag ≥ 5.2 ng/mL, as well as high risk factors for CILN and/or PALN metastasis, should undergo resection of enlarged lymph nodes below the common iliac gland and lymphadenectomy of CILN/PALN to reduce tumor burden and to clarify lymph node metastasis status for accurate guidance in follow-up treatment. Patients with MAD < 1.0 cm and SCC-Ag < 5.2 ng/mL may be treated with chemoradiotherapy directly based on imaging, given the low lymph node metastasis rate.

The value of combined detection of CEA, CYFRA21-1, SCC-Ag, and pro-GRP in the differential diagnosis of lung cancer.

BACKGROUND: To investigate the value of carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC-Ag), and gastrin-releasing peptide (pro-GRP) in the differential diagnosis of lung cancer. METHODS: We enrolled 120 patients with malignant lung cancer who were treated at our hospital between June 2018 to June 2020. A further 58 patients with benign lung tumors and 60 healthy volunteers were also enrolled. Serum levels of CEA, CYFRA21-1, SCC-Ag, and pro-GRP were determined and compared across different populations, different pathological types, and different TNM stages. An ROC curve was drawn to evaluate the value of the four indicators when combined for the diagnosis of lung cancer. RESULTS: The levels of CEA, CYFRA21-1, SCC-Ag, and pro-GRP in the malignant group were significantly higher than those in the benign and healthy groups (P<0.05). CEA in adenocarcinoma was significantly higher than that in squamous cell carcinoma (SCC) and small cell carcinoma (P>0.05), and CYFRA21-1 in non-small cell carcinoma was significantly higher than that in small cell carcinoma (P<0.05). Pro-GRP in small cell carcinoma was significantly higher than that in non-small cell carcinoma (P<0.05), and the SCC-Ag level in SCC was significantly higher than that in small cell carcinoma and adenocarcinoma (P<0.05). There was no statistically significant difference in CEA among various pathological types (P>0.05). However, there were significant differences in the levels of CEA and pro-GRP in different TMN stages (P<0.05), and in the levels of CEA and pro-GRP in different TMN stages (P<0.05) where from stage I to stage IV CEA, pro -GRP levels increased. There was a significant difference in CYFRA21-1 levels in stages I-III (P<0.05), and in stages III and IV, although there was no statistically significant difference in SCC-Ag in different stages (P>0.05). The area under the curve (AUC) for the combined diagnosis of lung cancer with the four markers was 0.9250 (95% CI: 0.8866-0.9634), the sensitivity was 93.29%, and the specificity was 84.32%. CONCLUSIONS: Joint inspection of CEA, CYFRA21-1, SCC-Ag, and pro-GRP levels has certain clinical value for the differential diagnosis of lung cancer.

Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review.

BACKGROUND: Cervical cancer screening is slowly transitioning from Pappanicolaou cytologic screening to primary Visual Inspection with Acetic Acid (VIA) or HPV testing as an effort to enhance early detection and treatment. However, an effective triage tests needed to decide who among the VIA or HPV positive women should receive further diagnostic evaluation to avoid unnecessary colposcopy referrals is still lacking. Evidence from experimental studies have shown potential usefulness of Squamous Cell Carcinoma Antigen (SCC Ag), Macrophage Colony Stimulating Factor (M-CSF), Vascular Endothelial Growth Factor (VEGF), MicroRNA, p16INKa / ki-67, HPV E6/E7/mRNA, and DNA methylation biomarkers in detecting premalignant cervical neoplasia. Given the variation in performance, and scanty review studies in this field, this systematic review described the diagnostic performance of some selected assays to detect high-grade cervical intraepithelial neoplasia (CIN2+) with histology as gold standard. METHODS: We systematically searched articles published in English between 2012 and 2020 using key words from PubMed/Medline and SCOPUS with two reviewers assessing study eligibility, and risk of bias. We performed a descriptive presentation of the performance of each of the selected assays for the detection of CIN2 + . RESULTS: Out of 298 citations retrieved, 58 articles were included. Participants with cervical histology yielded CIN2+ proportion range of 13.7-88.4%. The diagnostic performance of the assays to detect CIN2+ was; 1) SCC-Ag: range sensitivity of 78.6-81.2%, specificity 74-100%. 2) M-CSF: sensitivity of 68-87.7%, specificity 64.7-94% 3) VEGF: sensitivity of 56-83.5%, specificity 74.6-96%. 4) MicroRNA: sensitivity of 52.9-67.3%, specificity 76.4-94.4%. 5) p16INKa / ki-67: sensitivity of 50-100%, specificity 39-90.4%. 6) HPV E6/E7/mRNA: sensitivity of 65-100%, specificity 42.7-90.2%, and 7) DNA methylation: sensitivity of 59.7-92.9%, specificity 67-98%. CONCLUSION: Overall, the reported test performance and the receiving operating characteristics curves implies that implementation of p16ink4a/ki-67 assay as a triage for HPV positive women to be used at one visit with subsequent cryotherapy treatment is feasible. For the rest of assays, more robust clinical translation studies with larger consecutive cohorts of women participants is recommended.

Combined Detection of ACTN4 and SCC-Ag is a Promising Serological Biomarker for Cervical Intraepithelial Neoplasia 3 or Worse: A Case-Control Study.

PURPOSE: Cervical cancer (CC) is a common malignancy in women. Squamous cell carcinoma antigen (SCC-Ag) and cancer antigen (CA)-125 are widely used to help diagnose CC, but novel tumour markers with superior sensitivity and specificity are needed. α-Actinin 4(ACTN4) is overexpressed in CC, though its diagnostic value for CC is unclear. This study examined the diagnostic value of ACTN4 and SCC-Ag as biomarkers for cervical intraepithelial neoplasia (CIN) 3 or worse. METHODS: Women screened for CC at Fujian Medical University Union Hospital were recruited from 2017.1 to 2018.5. Cervical tissues and blood were collected at the same time. Patients pathologically diagnosed as CIN3+ or NILM/CIN1/CIN2 were classified into the case and control groups, respectively. ACTN4 mRNA and protein levels were detected through quantitative PCR and immunohistochemistry, respectively, and ACTN4 and SCC-Ag concentrations were analysed by ELISA. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood rate (PLR), negative likelihood rate (NLR), and Youden index (YI) of ACTN4 and SCC-Ag were evaluated. The optimum cut-off points for ACTN4 and SCC-Ag were determined by receiver operating characteristic (ROC) curve analysis, and accuracy was evaluated by the area under the ROC curve. RESULTS: In total, 105 patients were classified as CIN3+ cases and 106 as controls. The median ACTN4 levels in case and control tissues were 10.6 and 4.15, respectively. The ACTN4 and SCC-Ag concentrations were significantly higher in cases than controls (PACTN4=0.0007; PSCC-Ag=0.0067). The sensitivity, specificity, PPV, NPV, PLR, NLR and YI of ACTN4 were 68.6%, 76.3%, 76.3%, 72.5%, 2.89, 0.41 and 44.9, respectively; SCC-Ag had a similar diagnostic value (P>0.05), and ACTN4 combined with SCC-Ag had a superior diagnostic value (75.6%, 87.5%, 88.6%, 73.7%, 6.05, 0.28, and 63.1, respectively). CONCLUSION: Combined ACTN4 and SCC-Ag detection is a promising serological biomarker for patients with CIN3 or worse.

Detection of Recurrent Cervical Cancer and Prediction of Its Patient Survival with Serum Squamous-Cell Carcinoma-Antigen and 2-[18F] Fluoro-2-Deoxy-d-Glucose-Positron Emission Tomography/Computed Tomography.

AIM: To evaluate the usefulness of serum squamous-cell carcinoma antigen (SCC-Ag) and 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) for the detection of recurrent squamous-cell carcinoma (SqCC) of the uterine cervix, and its prediction of patient survival. METHODS: FDG-PET/CT was performed for patients with serum SCC-Ag levels elevated to ≥1.5 ng/mL (Group 1) and those with suspicious recurrences without any increase in serum SCC-Ag levels (Group 2). The results were analyzed on the basis of histological data, disease progression and/or clinical follow-up. Recurrence was defined as evidence of recurrent lesions within 6 months of FDG-PET/CT. The outcome was determined using medical records. RESULTS: In total, 88 consecutive patients with cervical SqCC cancer with suspected recurrence (62 in Group 1 and 26 in Group 2) were enrolled. Recurrences were observed in 55 patients (77.4% (48/62) in Group 1 vs. 26.9% (7/26) in Group 2, p < 0.001). The overall sensitivity, specificity and accuracy of serum SCC-Ag were 87.3%, 57.6% and 76.1%, respectively, and those of FDG-PET/CT were 98.2%, 90.9% and 95.5%, respectively; the corresponding values were 97.9%, 92.9% and 96.8% for Group 1 and 100%, 89.5% and 92.3% for Group 2. Surgical resection was performed for 16 patients. At the end of the study, 40.3% (25/62) of Group 1 patients and 88.5% (23/26) of Group 2 patients were alive (p < 0.001). The survival of patients who underwent surgical resection for recurrent tumors was higher than that of patients who did not undergo resection (62.5% (10/16) vs. 17.9% (7/39), p = 0.001). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from FDG-PET/CT showed significantly different in-patient survival. CONCLUSIONS: Serum SCC-Ag could predict tumor recurrence and the survival of patients with SqCC cervical cancer. As such, the surgical resection of limited recurrent disease, as determined using FDG-PET/CT, might improve the survival of patients with cervical cancer. MTV and TLG may serve as a prognostic biomarker of survival in patients with recurrent cervical cancer.

Clinical Value of Tumor Marker Index Based on Preoperative CYFRA 21-1 and SCC-Ag in the Evaluation of Prognosis and Treatment Effectiveness in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: This study aimed to investigate the prognostic value of tumor marker index (TMI) based on preoperative cytokeratin 19 fragment (CYFRA 21-1) and squamous cell carcinoma antigen (SCC-Ag) and the relationship between preoperative TMI and treatment effectiveness of postoperative adjuvant chemotherapy for patients with esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Between January 2009 and December 2014, a total of 267 patients with ESCC who underwent radical resection were retrospectively enrolled. The TMI was defined as the geometric mean of normalized CYFRA 21-1 and SCC-Ag levels. The clinical and prognostic values of TMI were determined using univariate and multivariate survival analyses. RESULTS: Preoperative TMI level was associated with age, tumor size, pT stage, pN stage, and CYFRA 21-1, SCC-Ag, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) levels. The 5-year overall survival rate of patients with high TMI was significantly lower than that of patients with low TMI (P < 0.001). Univariate and multivariate analyses revealed that TMI (P = 0.031) was an independent prognostic factor. Patients with ESCC with high TMI level who underwent surgery combined with postoperative chemotherapy had a significantly better prognosis than those who underwent surgery alone (P = 0.015). However, no significant difference was observed in patients with low TMI level (P = 0.682). CONCLUSION: TMI as a prognostic indicator of ESCC is superior to CYFRA 21-1 and SCC-Ag. The TMI might be useful in predicting the therapeutic effectiveness of postoperative chemotherapy and selecting patients who may benefit from postoperative chemotherapy.

Diagnostic Value of Albumin to Fibrinogen Ratio in Cervical Cancer.

BACKGROUND: Albumin to fibrinogen ratio (AFR) play a crucial role in the progression and prognosis of many malignant tumors. This study aimed to comprehensively assess the diagnostic value of AFR as single markers or in combination with squamous cell carcinoma antigen (SCC-Ag), cancer antigen 125 (CA-125) in cervical cancer. METHODS: A total of 323 cervical cancer inpatients, 143 patients with cervical intraepithelial neoplasia (CIN) and 317 healthy controls were analyzed. Differences in laboratory parameters and clinicopathological features were calculated using the Mann-Whitney U or Kruskal-Wallis H test. The receiver operating characteristic (ROC) curve was used to evaluate the predicted value of AFR, alone or combined with SCC-Ag, CA-125 for the diagnosis of cervical cancer. RESULTS: The levels of AFR in patients with cervical cancer were significantly lower than those in the CIN patients and the control subjects. AFR were not only negatively correlated with the tumor stage, but also related to histology typing, lymph node metastasis, distant metastasis, depth of stromal infiltration, tumor size, and tumor stage; however, it was not associated with the blood group. AFR combined with SCC-Ag possessed a larger area under the curve (AUC; AUCAFR+SCC-Ag = 0.924, 95% confidence interval (CI) 0.900, 0.944) than AFR (P < 0.001), SCC-Ag (P < 0.001), or CA-125 (P < 0.001) did alone. CONCLUSIONS: The pretreatment levels of AFR, alone or combined with SCC-Ag, CA-125 could improve the diagnostic efficiency of cervical cancer.

Serum miR-638 Combined with Squamous Cell Carcinoma-Related Antigen as Potential Screening Biomarkers for Cervical Squamous Cell Carcinoma.

Aims: Cervical cancer is the second most common cause of cancer-related deaths in developing nations. Human papillomavirus prophylactic vaccines are not widely available, and there are shortages of gynecologists and cytologists in the already overburdened health care systems. The aim of this study was to identify circulating microRNAs (miRNAs) that could be used as feasible screening tests for cervical cancer in low-resource regions. Materials and Methods: Serum expression levels of five miRNAs were measured and validated by quantitative real-time polymerase chain reaction in cervical squamous cell carcinoma (CSCC) patients, cervical intraepithelial neoplasia patients, and healthy individuals. Squamous cell carcinoma-related antigen (SCC-Ag) was also measured in the serum. Results: Serum miR-638, miR-203a-3p, miR-1914-5p, and miR-521 levels were downregulated in the CSCC group (p < 0.05). Receiver operating characteristic (ROC) curve analysis indicated that the area under the ROC curve (AUC) values for miR-638 and miR-521 were 0.734 and 0.742, respectively, for discriminating CSCC patients from healthy controls. Furthermore, the combined use of miR-638 and SCC-Ag yielded the best screening performance and increased the AUC value, sensitivity, and specificity to 0.956, 94.87%, and 80.00%, respectively. Conclusion: This study suggested that miR-638 and miR-521 have independent screening value and that the combined measurement of miR-638 and SCC-Ag resulted in a better ability to discriminate patients with CSCC from healthy individuals.

Prognostic significance of serum carcinoembryonic antigen and squamous cell carcinoma antigen in patients with esophageal squamous cell carcinoma undergoing radical esophagectomy.

BACKGROUND: It is generally believed that the preoperative serum carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) levels are independent predictors of prognosis in multiple malignant tumors. However, their predictive value in esophageal squamous cell carcinoma (ESCC) is still unknown. Therefore, the main purpose of this study is to detect the serum CEA and SCC-Ag levels of ESCC patients before operation, in order to clarify the clinical significance of them as prognostic factors. METHODS: We conducted a retrospective review of 348 patients with ESCC treated by esophagectomy between February 2009 and October 2012. We Analyzed the influence of serum CEA and SCC-Ag level on prognosis. We used a receiver operating characteristic (ROC) curve to identify the serum CEA and SCC-Ag level for predicting survival. We used Log-rank test to compare survival curves, and Cox regression analysis to clarify significant prognostic factors. RESULTS: The cutoffs for CEA and SCC-Ag were 2.28 ng/mL and 0.75 ng/mL, respectively, Under curve area of CEA was 0.600 (95% CI: 0.541-0.660; P=0.001) and under curve area of SCC-Ag was 0.567 (95% CI: 0.507-0.628; P=0.030). According to the Kaplan-Meier curves, the overall survival rate (OS) and disease-free survival rate (DFS) of patients with CEA ≤2.28 ng/mL were higher than those with CEA >2.28 ng/mL. Meanwhile, patients with serum levels of SCC-Ag ≤0.75 ng/mL had a more favorable OS and DFS than those of patients with SCC-Ag >0.75 ng/mL. Cox regression analysis showed that the total mortality of patients with CEA >2.28 ng/mL was higher than that of patients with CEA ≤2.28 ng/mL (HR 1.76; 95% CI: 1.39-2.39; P<0.001). Additionally, SCC-Ag >0.75 ng/mL was an independent negative prognostic factor for DFS (HR 1.86; 95% CI: 1.17-2.96; P=0.009). As the nomogram showed, the survival rate of ESCC patients with high preoperative serum CEA and SCC-Ag levels was relatively low. CONCLUSIONS: High levels of serum CEA and SCC-Ag were independent and significant predictors of ESCC patients after surgical treatment.

Predictive significance of CYFRA21-1, squamous cell carcinoma antigen and carcinoembryonic antigen for lymph node metastasis in patients with esophageal squamous cancer.

From January 2018 to May 2018, 108 patients with thoracic esophageal cancer underwent esophagectomy with two- to three-field lymph node dissection. Serum cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), squamous cell carcinoma antigen, and carcinoembryonic antigen levels were detected before surgery. Preoperative serum levels of CYFRA21-1 and squamous cell carcinoma antigen were correlated closely with pN stage (P = 0.000 and P = 0.045). CYFRA21-1 and pathological T status were independent predictors of lymph node metastasis (P = 0.000). The area under the curve values of CYFRA21-1 and squamous cell carcinoma antigen for predicting lymph node metastasis were 0.731 (P =0.000) and 0.650 (P =0.007), respectively. Our study demonstrated that serum CYFRA21-1 and squamous cell carcinoma antigen levels were associated with lymph node metastasis in esophageal squamous cell carcinoma, especially in patients at the early T stage. The preoperative serum CYFRA21-1 level was an independent predictor of lymph node metastasis.

Squamous cell carcinoma antigen concentration in fine needle aspiration samples: A new method to detect cervical lymph node metastases of head and neck squamous cell carcinoma.

BACKGROUND: The purpose of this study was to determine the additional diagnostic value of squamous cell carcinoma antigen (SCC-Ag) in cervical lymph node fine needle aspiration (FNA) samples for the detection of regional metastases of head and neck squamous cell carcinoma (HNSCC). METHODS: In 149 FNA samples of 114 patients, SCC-Ag concentration was retrospectively analyzed and associated with diagnosis to establish a cutoff concentration in relation to sensitivity and specificity of HNSCC detection. RESULTS: SCC-Ag was elevated in lymph nodes from patients with HNSCC compared to lymph nodes from other patients (P < 0.01). With 0.3 µg/L as the cutoff concentration, SCC-Ag has 96% sensitivity for detecting HNSCC. CONCLUSIONS: SCC-Ag in FNA is a reliable test for detecting HNSCC in cervical lymph nodes.