Squamous Cervical Cancer Research Articles

Septin9 DNA methylation as a promising biomarker for cervical cancer

Aberrant Septin9 methylation in cervical cancer has been rarely studied. We aimed to identify its diagnostic value in cervical cancer using cervical scrapings, and its predictive potential in plasma for pelvic nodal metastasis of cervical cancer. The statuses of methylated Septin9 in fresh cervical lesions and cervical scrapings were first evaluated by using quantitative methylation-specific PCR. Subsequently, the relationship between Septin9 methylation in 113 plasma samples and pelvic nodal metastasis of cervical cancer was evaluated. Methylated Septin9 was detected in all cancerous tissues, but not in cervicitis. The degrees of Septin9 methylation increased with growing severity of cervical lesions in cervical scrapings. The sensitivity of methylated Septin9 was lower than that of cytology, while it yielded a high specificity and area under the curve in detecting high-grade squamous intraepithelial lesion or cervical cancer; and when Septin9 methylation combined with HPV16/18 genotyping, the sensitivity would increase from 70.42% to 82.39%. Plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%. In conclusion, we demonstrated methylated Septin9 to be an innovative diagnostic biomarker for cervical cancer and its non-invasive predictive potential in plasma for pelvic nodal metastasis of cervical cancer. Impact statement What is already known on this subject? The occurrence of cervical cancer is related to Septin9 methylation. In fresh specimens and cervical scrapings, we found the degrees of methylated Septin9 increased with growing severity of cervical lesions. Compared with HPV16/18 genotyping and cytological detection, Septin9 methylation had a better specificity and AUC in detecting ≥ HSIL. Furthermore, plasma-based Septin9 methylation also had a high specificity for pelvic lymphatic metastasis prediction. What the results of this study add? Methylation analysis of Septin9 indicated a similar sensitivity, specificity and AUC in detecting ≥ HSIL, relative to HPV16/18 genotyping. Compared with cytological method, Septin9 methylation also yielded a higher specificity and AUC in detecting ≥ HSIL. And we also found plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%; additionally an increasing sensitivity from 50% to nearly 80% was found when combined with SCCAg. What the implications are of these findings for clinical practice and/or further research? This study aimed to evaluate the relationship between Septin9 methylation and cervical cancer, and to explore the value of methylated Septin9 in the detection of cervical (pre)cancerous lesions. Moreover, we would explore plasma-based ctDNA biomarkers for pelvic lymphatic metastasis prediction of cervical cancer, to improve non-invasive predictive accuracy of pelvic nodal metastasis and reduce the complications caused by pelvic lymphadenectomy.

Long-read sequencing reveals oncogenic mechanism of HPV-human fusion transcripts in cervical cancer

Integration of high-risk human papillomavirus (HPV) into the host genome is a crucial event for the development of cervical cancer, however, the underlying mechanism of HPV integration-driven carcinogenesis remains unknown. Here, we performed long-read RNA sequencing on 12 high-grade squamous intraepithelial lesions (HSIL) and cervical cancer patients, including 3 pairs of cervical cancer and corresponding para-cancerous tissue samples to investigate the full-length landscape of cross-species genome integrations. In addition to massive unannotated isoforms, transcriptional regulatory events, and gene chimerism, more importantly, we found that HPV-human fusion events were prevalent in HPV-associated cervical cancers. Combined with the genome data, we revealed the existence of a universal transcription pattern in these fusion events, whereby structurally similar fusion transcripts were generated by specific splicing in E6 and a canonical splicing donor site in E1 linking to various human splicing acceptors. Highly expressed HPV-human fusion transcripts, eg, HPV16 E6*I-E7-E1SD880-human gene, were the key driver of cervical carcinogenesis, which could trigger overexpression of E6*I and E7, and destroy the transcription of tumor suppressor genes CMAHP, TP63 and P3H2. Finally, evidence from in vitro and in vivo experiments demonstrates that the novel read-through fusion gene mRNA, E1-CMAHP (E1C, formed by the integration of HPV58 E1 with CMAHP), existed in the fusion transcript can promote malignant transformation of cervical epithelial cells via regulating downstream oncogenes to participate in various biological processes. Taken together, we reveal a previously unknown mechanism of HPV integration-driven carcinogenesis and provide a novel target for the diagnosis and treatment of cervical cancer.

S2784 A Case of Delayed Cervical Cancer Diagnosis in a Patient With Crohn’s Disease

Introduction: Increased cancer risk in inflammatory bowel disease (IBD) is thought to be due to immunosuppression from biologic therapy and/or inflammation. Women with IBD have an increased risk of melanoma and adenocarcinoma of the small bowel and colon, and those that are on an immunosuppressive regimen that includes azathioprine have an additional increased risk of lymphoma and squamous cell carcinoma of the skin and cervix. Here we present a case of a patient with an atypical and rare malignancy, whose diagnosis was delayed due to overlap in the symptoms of the malignancy and her known IBD diagnosis. Case Description/Methods: A woman in her mid 40s with a 28-year history of colonic Crohn’s disease maintained on ustekinumab injection. She was previously taking azathioprine for 7 years and initially responded to adalimumab, but after a flare, was switched to ustekinumab with symptomatic and endoscopic response. She then presented to her gynecologist in November 2020 with complaints of bloating and large amounts of clear vaginal discharge. A cervical exam and routine pap smear of the ectocervix showed normal cytology. Eight months later, the patient presented to her gastroenterologist with worsening bloating, hematochezia, left lower quadrant pain, and persistent vaginal discharge. The patient was concerned for an IBD flare, but noted that the abdominal bloating and vaginal discharge were different than her usual flare. After CT abdomen/pelvis revealed 2 large pelvic complex cystic lesions, her biologic was stopped and she underwent a hysterectomy with bilateral salpingo-oophorectomy. Pathology revealed non-HPV associated invasive moderately differentiated gastric-type endocervical adenocarcinoma. She completed treatment with an anti-VEGF antibody, but a restaging PET scan six months later showed uptake consistent with peritoneal carcinomatosis. Discussion: This immunosuppressed patient had an advanced and aggressive non-HPV endocervical cancer which was missed on ectocervical pap smear. Pap smears that include inadequate endocervical samples are considered suboptimal, but are usually not grounds for further testing in the average patient. However, Crohn’s disease patients have increased risk of low- and high-grade squamous epithelial cervical lesions and cervical cancer compared to women without IBD, likely due to a combination of elevated inflammatory state and immunosuppressive medications. Cervical cancer screening in immunosuppressed patients with IBD should include adequate endocervical sampling.

Pllans-II Induces Cell Death in Cervical Cancer Squamous Epithelial Cells via Unfolded Protein Accumulation and Endoplasmic Reticulum Stress.

Due to the lack of chemotherapeutic drugs that selectively affect cervical cancer cells, natural sources such as snake venom are currently being investigated for molecules with antitumor potential. Pllans–II, a phospholipase A2 type–Asp49 from Porthidium lansbergii lansbergii snake venom, induced cell death in a cervical cancer cell line—Ca Ski—related to dysfunction in the ability to resolve endoplasmic reticulum stress, evidenced by sub–expression of genes such as PERK, ERO1 PDIs, HSP70, and CHOP. Western blot analysis validated the last two genes′ sub–expression at the protein level. In addition, Pllans–II presented a dose–dependent cytotoxic effect on cancer cells and an insignificant effect on healthy endothelial cells (HUVEC). Additionally, Pllans–II inhibited cancer cells′ adhesion and migration capacity, induced cell cycle arrest in the G2/M phase, and induced apoptosis stimulated possibly by the extrinsic route. These results demonstrate for the first time that Pllans–II has an antitumor effect on a squamous epithelial cervical cancer cell line and represents a possible biotechnological tool for designing a prominent antitumor agent.

S3519 A Rare Case of Epigastric Pain Caused by Duodenal Metastatic Cervical Cancer

Introduction: Cervical cancer was previously one of the most common causes of death for women in the United States but survival has since improved with the use of screening and the HPV vaccine. Metastatic cervical cancer spread to the duodenum is rare and presents a diagnostic challenge due to vague symptoms. We present a case of epigastric pain caused by invasive squamous cell cervical cancer with duodenal metastasis. Case Description/Methods: A 59-year-old female with a history of GERD and treated cervical cancer (2 years prior) and currently on pembrolizumab presented to clinic for 3 months of progressive upper abdominal pain and dyspepsia. Last upper endoscopy a year ago was normal. Physical exam was notable for epigastric tenderness without guarding. Laboratory data was remarkable for downtrending hemoglobin, normal liver function tests, normal lipase, and negative stool H pylori antigen. She was referred for EGD. A contrasted CT of the abdomen and pelvis performed revealed multiple enlarged lymph nodes of the mesentery. Upper endoscopy revealed thickened folds of the second portion of the duodenum and multiple biopsies taken of this site. It was an otherwise normal upper endoscopy. The duodenal biopsies were positive for metastatic squamous cancer of the cervix. The patient was transitioned to treatment with gemcitabine and carboplatin due to progressive disease on pembrolizumab. She unfortunately succumbed to her disease six months later. (Figure) Discussion: There is an estimated 7.5 per 100,000 new cases of cervical cancer per year with death rate of 2.2 per 100,000 in the United States. Cervical cancer is usually locally invasive and spreads by lymphatics or hematogenously with most common metastatic sites of lungs, liver, and bone. In a previous review, liver metastases was in up to 12.5% of patients but did not mention a single case of luminal disease. It is very rare for most cancers to metastasize to the gastrointestinal tract, but when present, metastasis has a predilection for the stomach and duodenum. Few case reports are available for cervical cancer metastasis to the GI tract specifically, with about 16 identified. These patients generally presented with gastrointestinal bleeding, bowel perforation, nonspecific abdominal pain or obstructive symptoms. In conclusion, duodenal metastasis of cervical cancer is rare and can be frequently missed. A high degree of suspicion can expedite referral for upper endoscopy to diagnose and allow for treatment to extend patients’ quality of life.Figure 1.: Thickened folds in the second portion of duodenum.

Radiomic Analysis for Pretreatment Prediction of Recurrence Post-Radiotherapy in Cervical Squamous Cell Carcinoma Cancer.

Background: The current study aims to predict the recurrence of cervical cancer patients treated with radiotherapy from radiomics features on pretreatment T1- and T2-weighted MR images. Methods: A total of 89 patients were split into model training (63 patients) and model testing (26 patients). The predictors of recurrence were selected using the least absolute shrinkage and selection operator (LASSO) regression. The machine learning used neural network classifiers. Results: Using LASSO analysis of radiomics, we found 25 features from the T1-weighted and 4 features from T2-weighted MR images, respectively. The accuracy was highest with the combination of T1- and T2-weighted MR images. The model performances with T1- or T2-weighted MR images were 86.4% or 89.4% accuracy, 74.9% or 38.1% sensitivity, 81.8% or 72.2% specificity, and 0.89 or 0.69 of the area under the curve (AUC). The model performance with the combination of T1- and T2-weighted MR images was 93.1% accuracy, 81.6% sensitivity, 88.7% specificity, and 0.94 of AUC. Conclusions: The radiomics analysis with T1- and T2-weighted MR images could highly predict the recurrence of cervix cancer after radiotherapy. The variation of the distribution and the difference in the pixel number at the peripheral and the center were important predictors.

MRI outcome evaluation in patients with IB2 and IIA2 squamous cervical cancer stages: preliminary results

ObjectivesTo evaluate the therapeutic effect of neoadjuvant therapy (NAT) followed by radical hysterectomy and concurrent chemoradiotherapy (CCRT) in stage IB2 and IIA2 squamous cervical cancer (SCC) and investigate the value of apparent diffusion coefficient (ADC) in outcome evaluation of different treatment strategies in the patients.MethodsA total of 149 patients with IB2 and IIA2 SCC who underwent pretreatment MRI and DWI scan were included. Patients were treated with NAT + RH or CCRT. Clinical indices and pathological factors were recorded. The imaging indices were measured including tumor size and tumor ADC values. Intraclass correlation coefficient was employed to evaluate the consistency of the indices measured by two observers. ROC curves were used to evaluate the cutoff values of clinical and imaging indices. Kaplan–Meier and Cox proportional hazard model were used to analyze the independent factors of disease-free survival (DFS).ResultsThe median follow-up period was 42.3 months. SCC-Ag, ADCmax and ADCmin were independent factors for DFS in the entire cohort. SCC-Ag, ADCmin and vascular invasion were independent factors for DFS in NAT + RH group. ADCmax and ADCmin were independent factors for DFS in CCRT group. ADCmin was the strongest independent factor for DFS in NAT + RH group, while ADCmax was that in CCRT group.ConclusionThe NAT + RH patients had similar DFS to that of CCRT in IB2 and IIA2 SCC, which could be a potential feasible alternative treatment. ADCmin and ADCmax were more valuable in evaluating the outcome of patients who underwent NAT + RH or CCRT, respectively.

Pilot Cervical Cancer Navigation Program Outcomes from a Tertiary Tanzanian Academic Institute (037)

Pilot Cervical Cancer Navigation Program Outcomes from a Tertiary Tanzanian Academic Institute (037)

Identification of critical genes associated with radiotherapy resistance in cervical cancer by bioinformatics.

BackgroundCervical cancer (CC) is one of the common malignant tumors in women, Currently, 30% of patients with intermediate to advanced squamous cervical cancer are still uncontrolled or recurrent after standard radical simultaneous radiotherapy; therefore, the search for critical genes affecting the sensitivity of radiotherapy may lead to new strategies for treatment.MethodsFirstly, differentially expressed genes (DEGs) between radiotherapy-sensitivity and radiotherapy-resistance were identified by GEO2R from the gene expression omnibus (GEO) website, and prognosis-related genes for cervical cancer were obtained from the HPA database. Subsequently, the DAVID database analyzed gene ontology (GO). Meanwhile, the protein-protein interaction network was constructed by STRING; By online analysis of DEGs, prognostic genes, and CCDB data that are associated with cervical cancer formation through the OncoLnc database, we aim to search for the key DEGs associated with CC, Finally, the key gene(s) was further validated by immunohistochemistry.Result298 differentially expressed genes, 712 genes associated with prognosis, and 509 genes related to cervical cancer formation were found. The results of gene function analysis showed that DEGs were mainly significant in functional pathways such as variable shear and energy metabolism. By further verification, two genes, ASPH and NKAPP1 were identified through validation as genes that affect both sensitivities to radiotherapy and survival finally. Then, immunohistochemical results showed that the ASPH gene was highly expressed in the radiotherapy-resistant group and had lower Overall survival (OS) and Progression-free survival (PFS).ConclusionThis study aims to better understand the characteristics of cervical cancer radiation therapy resistance-related genes through bioinformatics and provide further research ideas for finding new mechanisms and potential therapeutic targets related to cervical cancer radiation therapy.

The role of selenoprotein P in the determining the sensitivity of cervical cancer patients to concurrent chemoradiotherapy: A metabonomics-based analysis

BackgroundThe effect of selenoprotein P (SELENOP) levels on the sensitivity of cervical cancer patients to concurrent chemoradiotherapy (CCRT) has not been reported. In this study, the effects of the variations in plasma SELENOP levels on the sensitivity of cervical cancer patients to CCRT were investigated using metabonomics. MethodsTwo patient groups were evaluated, i.e., the case group: 11 patients with intermediate to advanced primary squamous cervical cancer, who developed resistance against CCRT, and the sensitivity group: 11 patients who did not develop resistance were matched in a 1:1 ratio (controls). Blood samples were collected before and after CCRT, and the plasma SELENOP levels were measured by ELISA. The different metabolites present in the plasma were analyzed by UPLC-MS-MS. ResultsSELENOP levels exhibited a significant reduction in both the resistant and sensitive groups after CCRT (F = 50.705, P < 0.001), and interaction effects between sensitivity and pre-and post-treatment on SELENOP levels were observed (F = 7.414, P = 0.013). Further, a more significant reduction in the SELENOP levels was observed in the CCRT-resistant group (mean reduction, 0.028 µg/mL; P < 0.001) than in the sensitive group (mean reduction, 0.013 µg/mL; P = 0.006). Four metabolic biomarkers, i.e., C18, C19, C20 sphingomyelin, and phosphatidylcholine 20:2/22:6, were shown to be differentially expressed between the resistant and sensitive groups pre-and post-treatment. C20 sphingomyelin levels exhibited a significant correlation with SELENOP levels (r = −0.326, P = 0.031). ConclusionThe levels of plasma SELENOP in the CCRT-resistant group decreased significantly, suggesting that SELENOP might affect the sensitivity by modulating lipid synthesis and metabolism.

Informativity of Locally Estimated Odd-Numbered Higher Fatty Acids for Differential Diagnosis of HSIL and Cervical Cancer

Background. Current issues in the cytological assessment of cervical epithelium can hamper differential diagnosis of high-grade squamous intraepithelial lesion (HSIL) and cervical cancer.Aim. To determine the informativity of locally estimated values of odd-numbered higher fatty acids as differential markers in HSIL and cervical cancer.Materials and methods. Previous original data on the higher fatty acids content in cervical biopsy of primary pre-treatment HSIL and cervical cancer patients were analysed retrospectively. The study cohorts: clinical cohort I — 30 HSIL patients; clinical cohort II — 45 primary stage I squamous cervical cancer patients. Statistical methods included the analyses of ROC curves, sensitivity (Se), specificity (Sp) and accuracy (Ac).Results. Among all odd-numbered higher fatty acids, the following molecular markers (local thresholds) are differential for cervical cancer: C15:0 ≤1.91 %/cell (Se = 0.81; Sp = 0.84; Ac = 0.83; AUC = 0.81); C15:1 ≤1.72 %/cell (Se = 0.96; Sp = 0.91; Ac = 0.92; AUC = 0.96); C17:0 ≤2.95 %/cell (Se = 0.94; Sp = 0.93; Ac = 0.97; AUC = 0.97); C17:1 ≤1.11 %/cell (Se = 0.96; Sp = 0.98; Ac = 0.96; AUC = 1.0); C19:0 ≤1.17 %/cell (Se = 1.0; Sp = 1.0; Ac = 1.0; AUC = 1.0).Discussion. Tumour cells are known to possess atypical metabolism, which produces large amounts of higher fatty acids with odd numbers of carbon atoms. The study focused on the value of locally estimated odd-numbered higher fatty acids as differential molecular markers in HSIL and cervical cancer.Conclusion. The results suggest that C19:0 estimates are applicable in diagnosis of HSIL and cervical cancer.

Assessment of Response Rate and Toxicity in Locally Advanced Squamous Cell Carcinoma Cervix with Induction Chemotherapy Followed by Radiotherapy in Comparison with Concurrent Chemoradiation

Objective: To compare the toxicity, response rate, and survival of concurrent chemo radiotherapy and induction chemotherapy followed by radiotherapy alone in squamous cell cervical cancer patients. Place and duration of study: Radiation Oncology Department of Nishtar Hospital for 1 year Study design: A comparative retrospective study Methodology: A total of 60 women were included in the study who have been diagnosed with stage IB2 to stage IIIB squamous cell cervical carcinoma. After passing the inclusion and exclusion criteria, patients were divided into two groups, a concurrent chemo radiotherapy group (30 patients) and a radiotherapy group (30 patients) by consecutive data sampling. All the patients were subject to external beam radiotherapy to the 45 Gy to whole pelvis with 15 MV X-rays 5 days/week by using the four-field technique. The patients in the radiotherapy group were given induction chemotherapy with cisplatin 50 mg/m2 every 21 days with paclitexal 175mg/m2 (2 cycles) followed by radiotherapy alone. For the patients of concurrent chemo radiotherapy, patients were administered 40 mg/m2 cisplatin weekly with radiations for 5 cycles. Results: The overall response rate for CCRT group and RT group was 65% (n=30) and 50% (n=30) respectively. The overall survival rate was 12 months and 8 months for the CCRT group and RT group respectively. Similarly, relapse-free survival was 10 months in CCRT patients and 6 months in RT patients. The rate of hematological toxicities was more in CCRT patients. The most common adverse effect was diarrhea with 3 (10%) patients in the CCRT and 2 (6.6%) patients in the RT group. No deaths occurred due to treatment. Conclusion: The efficacy and toxicity of CCRT show promising results in squamous cell cervical carcinoma patients as compared to induction chemotherapy followed by radiotherapy treatment alone. Keywords: Concurrent chemoradiotherapy. Radiotherapy, squamous cell cervical carcinoma, toxicity

HNF1A-AS1: A Tumor-associated Long Non-coding RNA.

Hepatocyte nuclear factor 1 homeobox A antisense RNA 1 (HNF1A-AS1) is a Long non-coding RNA (LncRNA) that participates in the occurrence and development of lots of tumors and is supposed to be a new biomarker. The text aims to illustrate the biological effect, specific mechanism and clinical significance of HNF1A-AS1 in various tumors. Via consulting the literature, analyze and summarize the relationship between HNF1A-AS1 and all kinds of tumors and the specific mechanism. This is a review paper about the tumor-associated long non-coding RNA HNF1A-AS1. Many researches show that LncRNA HNF1A-AS1 is related to the development of tumorous tumors. Its expression is up-regulated in numerous tumors, such as oral squamous cell carcinoma, hepatocellular carcinoma, breast cancer, osteosarcoma, lung cancer, cervical cancer, bladder cancer, colon cancer, colorectal cancer, oesophageal adenocarcinoma and laryngeal squamous cell carcinoma. However, HNF1A-AS1 is down-regulated in gastroenteropancreatic, neuroendocrine neoplasms, oral squamous cell carcinoma. Furthermore, HNF1A-AS1 can affect tumor proliferation, invasion, migration and apoptosis by targeting some microRNAs-miR-661 and miR-124. HNF1A-AS1 can also influence the development of tumors by regulating EMT. These studies show that LncRNA-HNF1A-AS1 is closely related to the occurrence development of numerous cancers. Through various molecular mechanisms to regulate tumor growth, HNF1A-AS1 can possibly become the new biological biomarker and therapeutic target for many kinds of tumors.

Down-regulated expression of miR-99a is associated with lymph node metastasis and predicts poor outcome in stage IB cervical squamous cell carcinoma: a case-control study.

Background Lymph node metastasis (LNM) accounts for the most important route of metastasis for cervical cancer. Yet, the status of LNM is different in patients with similar clinico-pathological variables. It has been revealed that microRNAs are widely involved in the occurrence and development of various malignancies, and the tumor-suppressive or promoting effects of microRNA-99 (miR-99) family have been previously reported. This study sought to investigate the predictive value of miR-99a for lymphogenous spread and its effect on the survival of patients with early-stage cervical squamous cell cancer (CSCC).MethodsPatients with stage IB squamous cervical cancer who were treated surgically between October 2015 and November 2018 were enrolled. A total of 21 formalin-fixed paraffin-embedded tissues of pathologically confirmed positive lymph nodes were retrieved, and an additional 21 tissues of negative lymph nodes from patients well-matched on baseline characteristics were collected as the control group. TaqMan real-time quantitative polymerase chain reaction was used to examine the expression levels of miR-99a in the samples. Differential expression levels of miR-99a were compared between the 2 groups using independent sample t-test. Furthermore, the associations between miR-99a expression level and clinico-pathological parameters of these 42 patients was evaluated by Chi-square test or Fisher’s exact-probability method, and their effects on survival were assessed using Kaplan-Meier product-limit method.ResultsThere were no significant differences in baseline clinico-pathological parameters between the 2 groups (P>0.05). The expression levels of miR-99a in the node-positive group and control group were 1.61±3.09 and 16.77±30.40, respectively (P=0.029). Downregulated expression of miR-99a was closely related to depth of invasion (DOI) and lymph-vascular space invasion (P<0.05). Univariate analysis revealed that downregulated miR-99a and deeper DOI were associated with worse 5-year disease-free survival, while multivariate analysis showed that only the expression level of miR-99a was an independent factor for disease-free survival (HR =0.120; 95% CI: 0.015–0.979; P=0.048). Patients with downregulated miR-99a tended to have more unfavorable overall survival, but the difference did not reach statistical significance.Conclusions MiR-99a plays an inhibitory role in the pathogenesis of lymph node metastasis and may serve as a novel prognostic biomarker for patients with CSCC.

Implications of Persistent HPV52 and HPV58 Positivity for the Management of Cervical Lesions.

ObjectiveThis study aimed to compare the variability of HPV16/18/52/58 subtype infections in patients with different cervical lesions, to explore the guiding significance of persistent positive HPV subtypes 52 and 58 in the stratified management of cervical lesions, and to determine the appropriate management model.MethodThis study was conducted through a retrospective analysis of 244,218 patients who underwent HPV testing at the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University from September 2014 to December 2020 to examine the distribution of different types of HPV infection. From March 2015 to September 2017, 3,014 patients with known HPV underwent colposcopy to analyze high-risk HPV infection for different cervical lesions. Meanwhile, from September 2014 to December 2020, 1,616 patients positive for HPV16/18/52/58 alone with normal TCT who underwent colposcopy in our hospital were retrospectively analyzed for the occurrence of cervical and vulvovaginal lesions, with colposcopic biopsy pathology results serving as the gold standard for statistical analysis.ResultAnalysis of 244,218 patients who had HPV tested revealed that the top 3 high-risk HPV types were HPV52, HPV58, and HPV16. Further analysis of 3,014 patients showed that 78.04% of patients referred for colposcopy had HPV16/18/52/58 alone. Among high-grade squamous intraepithelial lesions (HSIL) and cervical cancer, the most common is HPV16, followed by HPV58 and then HPV52 (p < 0.05). A total of 1,616 patients with normal TCT who were referred for colposcopy due to HPV16/18/52/58 infection were further analyzed. Based on pathological findings in lesions of HSIL and CC, HPV16 is the most common, followed by HPV58 and then HPV18 (p < 0.05). In the 1,616 patients analyzed, high-grade vulvovaginal lesions were detected, with HPV58 being the most common, followed by HPV16 and then HPV52 (p < 0.05).Conclusion1. In patients with positive HPV58 alone and normal TCT, the indications for colposcopy may be relaxed, with particular attention paid to the possibility of vulvar and vaginal lesions.2. Patients with a positive HPV type 52 alone and normal TCT may be considered for a follow-up review and, if necessary, a colposcopy.3. The development of a more suitable HPV vaccine for the Asian population, such as HPV16/18/52/58, may better protect women’s health.

The Role of Calgranulin B Gene on the Biological Behavior of Squamous Cervical Cancer in vitro and in vivo [Retraction

[This retracts the article DOI: 10.2147/CMAR.S153036.].

Role of APOA1 in the resistance to platinum-based chemotherapy in squamous cervical cancer

BackgroundTo investigate the mechanism by which apolipoprotein A1 (APOA1) enhances the resistance of cervical squamous carcinoma to platinum-based chemotherapy.MethodsTwo cervical squamous carcinoma cell lines (SiHa and Caski) overexpressing APOA1 were constructed, treated with carboplatin, and compared to normal control cells.ResultsIn both SiHa and Caski cell lines, the clone-forming ability of CBP-treated cells was lower than that of untreated cells, and the change in the number of clones of overexpressing cells was lower than that of normal control cells (p < 0.05), indicating that APOA1 overexpression enhanced chemoresistance. A screen for APOA1 downstream proteins affecting platinum-based chemoresistance using Tandem Mass Tag revealed 64 differentially expressed proteins in SiHa cells, which were subjected to Gene Ontology (annotation, Kyoto Encyclopedia of Genes and Genomes enrichment, subcellular localization, structural domain annotation and enrichment, clustering, and interaction network analyses. Sixty-four differentially expressed proteins matching cancer-relavent association terms were screened and parallel response monitoring identified 29 proteins as possibly involved in the mechanism of platinum-based chemoresistance.ConclusionsOur analysis suggested that the mechanism may involve numerous regulatory pathways, including promoting tumor growth via the p38 MAPK signaling pathway through STAT1, promoting tumor progression via the PI3K signaling pathway through CD81 and C3, and promoting resistance to platinum-based chemotherapy resistance through TOP2A. The present study aimed to preliminarily explore the function and mechanism of APOA1 in platinum-based chemoresistance in cervical cancer, and the detailed mechanism needs to be further studied.

Prognostic Effect of Primary Recurrence Patterns in Squamous Cervical Carcinoma After Radical Surgery

ObjectiveTo examine the effect of primary recurrence patterns on the prognosis of squamous cervical cancer after initial treatment.MethodsPrimary recurrence patterns and prognostic factors were examined in stage IB-IIA cervical cancer patients after initial treatment. Recurrence site (locoregional recurrence and distant metastasis or in-field and out-field recurrence for patients receiving adjuvant radiotherapy) and subtype (nodal and organ recurrence) were examined. Clinicopathological characteristics and survival rates were evaluated to generate a prognostic nomogram.ResultsA total of 472 patients were included. The median follow-up period, 5-year overall (OS) rate, and median OS were 59.1 months, 33.7%, and 24.0 months, respectively. Overall, 38.8% and 61.2% of the patients had locoregional recurrence and distant metastasis, respectively, and survival rates were comparable in these groups. Patients with nodal recurrence had better OS than those with organ recurrence (38.3% vs 30.7%, respectively; P = 0.001). Patients not receiving adjuvant radiotherapy had increased risk of pelvic recurrence [odds ratio (OR) = 0.148; 95% confidence interval[(CI): 0.075–0.291, P = 0.000]. Positive lymph-vascular space invasion (OR= 1.928; 95% CI: 1.151–3.229, P = 0.013) and no chemotherapy (OR = 0.521; 95% CI: 0.317–0.733, P = 0.040) increased the risk of distant metastasis. Positive lymph node status after initial treatment were associated with nodal recurrence (OR = 3.729; 95% CI: 1.838–7.563, P = 0.000), while elevated preoperative squamous cell carcinoma antigen (SCC-Ag) levels were associated with organ recurrence (OR = 1.642; 95% CI: 1.325–2.265, P = 0.002). Recurrence subtype, therapy for relapse, the International Federation of Gynecology and Obstetrics stage, adjuvant radiotherapy, preoperative SCC-Ag levels, and risk subgroup were independently associated with OS.ConclusionsPrimary recurrence patterns were associated with specific clinicopathological characteristics of cervical cancer. Recurrent cervical cancer prognosis was mainly affected by recurrence location and subtype.

Review on Immuno-Oncology agents for Cancer Therapy

Until recently, cancer therapy comprised of four main types of treatment: surgery, radiotherapy, chemotherapy and targeted therapy. Over the past decade, immuno-oncology (IO) has emerged as a novel and important approach to cancer treatment through the stimulation of the body’s own immune system to kill cancer cells. This newly recognised method of treating cancer is rapidly developing, with many accelerated approvals by the US Food and Drug Administration and European Medicines Agency in 2019. Several therapeutic classes have emerged within IO, and are the focus of this review article. In particular, the immune checkpoint inhibitors have had remarkable success across multiple malignancies, and are the most well-established therapeutic class of IO agents to date. Biomarker testing for the programmed death-ligand 1 (PD-L1) checkpoint target has been developed and is now obligatory before treatment with pembrolizumab (Keytruda, Merck) when used for non-small-cell lung carcinoma, gastric cancer, head and neck squamous cell carcinoma and cervical cancer, as well as before treatment with atezolizumab (Tecentriq, Roche) when used for urothelial carcinoma. However, ambiguity remains as to the relevance of PD-L1 expression for checkpoint inhibition therapy for other tumour types. More recently, combining IO agents with conventional therapies has been evaluated with some significant improvements in patient outcomes. While IO agents are rapidly changing the standard of care for people with cancer, there are still many challenges to overcome in terms of managing their toxicities and ensuring that healthcare systems, such as the NHS, can afford the high cost of these therapies. The IO pipeline also includes chimeric antigen receptor T-cell therapies and cancer vaccines, both of which show great promise for the future but have their own unique toxicity and cost-effectiveness issues.

Review on Immuno-Oncology Agents for Cancer Therapy

Until recently, cancer therapy comprised of four main types of treatment: surgery, radiotherapy, chemotherapy and targeted therapy. Over the past decade, immuno-oncology (IO) has emerged as a novel and important approach to cancer treatment through the stimulation of the body’s own immune system to kill cancer cells. This newly recognised method of treating cancer is rapidly developing, with many accelerated approvals by the US Food and Drug Administration and European Medicines Agency in 2019. Several therapeutic classes have emerged within IO, and are the focus of this review article. In particular, the immune checkpoint inhibitors have had remarkable success across multiple malignancies, and are the most well-established therapeutic class of IO agents to date. Biomarker testing for the programmed death-ligand 1 (PD-L1) checkpoint target has been developed and is now obligatory before treatment with pembrolizumab (Keytruda, Merck) when used for non-small-cell lung carcinoma, gastric cancer, head and neck squamous cell carcinoma and cervical cancer, as well as before treatment with atezolizumab (Tecentriq, Roche) when used for urothelial carcinoma. However, ambiguity remains as to the relevance of PD-L1 expression for checkpoint inhibition therapy for other tumour types. More recently, combining IO agents with conventional therapies has been evaluated with some significant improvements in patient outcomes. While IO agents are rapidly changing the standard of care for people with cancer, there are still many challenges to overcome in terms of managing their toxicities and ensuring that healthcare systems, such as the NHS, can afford the high cost of these therapies. The IO pipeline also includes chimeric antigen receptor T-cell therapies and cancer vaccines, both of which show great promise for the future but have their own unique toxicity and cost-effectiveness issues.