Early Cervical Cancer Research Articles

Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria

BackgroundHigh risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC).MethodsThis was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC.ResultsWe enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43–58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC.ConclusionVaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.

CD39 Expression in Peripheral T Cells is Associated with Clinicopathological Characteristics in Patients with Cervical Cancer.

CD39 is an inhibitory checkpoint exerting rate-limiting effects on the ATP-adenosine pathway. It can be targeted to block adenosine-mediated immunosuppression. To analyze the relationship between the CD39 expression and clinicopathological characteristics including FIGO stage, lymph node and distant metastasis, and to further explore its potential role in cervical cancer. Peripheral blood was collected from 59 healthy people and 43 patients with cervical cancer. The percentage and absolute counts of CD3-positive, CD4-positive and CD8-positive T lymphocytes, CD4/CD8 ratio and the percentage of the CD39+ T cells in T lymphocytes were assessed by flow cytometry, and their correlations with clinical parameters were analyzed. Absolute numbers of CD8+ T lymphocytes, CD4/CD8 ratios, and the percentage of the CD39+ T cells were linked with FIGO stage, lymph node metastasis, and distant metastasis. The total numbers of CD8+ T lymphocytes were significantly higher in the peripheral blood of patients with cervical cancer in the early and middle stages than in the advanced stage. In addition, patients with early and middle-stage cervical cancer had considerably lower percentage of CD4+ CD39 + and CD8 + CD39 + T lymphocytes than those with advanced cervical cancer. These results suggest that the absolute counts of CD8+ T lymphocytes may be associated with the patient's prognosis and that the CD39 molecule, expressed on the surface of CD8+ T cells, is also related to FIGO stage, lymph node metastasis, and distant metastasis. CD39 expression on CD8-positive T cells exhibits a negative correlation with the number of CD8-positive T lymphocytes.

Digital droplet PCR-based quantification of ccfHPV-DNA as liquid biopsy in HPV-driven cervical and vulvar cancer.

More than 99% of cervical cancers and up to 40% of vulvar cancers are human papillomavirus (HPV) related. HPV 16 and 18 are the most relevant subtypes. Novel technologies allow the detection of minimal amounts of circulating cell-free HPV DNA (ccfHPV-DNA). The aim of this study was to evaluate ccfHPV-DNA assessed by droplet digital PCR (ddPCR) as a biomarker for molecular therapy monitoring in early, advanced, relapsed and metastatic HPV-driven cervical and vulvar cancer. Inclusion criteria of the study were histologically proven HPV 16/18-driven cervical and vulvar cancer with first diagnosed disease, newly diagnosed recurrence, or progression of disease. Blood samples were taken pre- and post-therapeutically. Circulating cell-free HPV DNA was quantified using ddPCR and the results were correlated with clinical data. The mean copy number of ccfHPV-DNA was 838.6 (± 3089.1) in pretreatment and 2.3 (± 6.4) in post-treatment samples (p < 0.05). The copy number of ccfHPV-DNA increased with higher FIGO stages (p < 0.05), which are commonly used for clinical staging/assessment. Furthermore, we compared the distribution of copy numbers between T-stage 1 versus T-stage 2/3. We could show higher copy number level of ccfHPV-DNA in T-stage 2/3 (p < 0.05). Therapy monitoring with determination of ccfHPV-DNA by ddPCR with a small amount of plasma reflects response to therapy and appears feasible for patients in advanced cancer stages of cervical and vulvar cancer. This promising tool should be examined as marker of therapy monitoring in particular in novel HPV-directed therapies.

Determinants of cervical cancer screening among women living with HIV in Zimbabwe.

In sub-Saharan Africa (SSA), cervical cancer (CC) is the second leading cause of cancer-related deaths, with human immunodeficiency virus (HIV) seropositive women being particularly vulnerable. Despite the benefits of early CC screening in reducing HIV-related CC deaths, CC screening uptake remains limited, with wide disparities in access across SSA. As part of a larger study, this paper examines the determinants of CC screening among HIV-seropositive women of reproductive age (15-49 years) in Zimbabwe. Using the 2015 Zimbabwe Demographic and Health Survey, we conducted multilevel analyses of CC screening among 1490 HIV-seropositive women, nested in 400 clusters. Our findings revealed that, even though 74% of HIV-seropositive women knew about CC, only 17.6% of them reported ever screening for it. Women who held misconceptions about HIV (OR = 0.47, p = 0.01) were less likely to screen for CC compared to those with accurate knowledge about HIV and CC. HIV-seropositive women with secondary or higher education were more likely to screen (OR = 1.39, p = 0.04) for CC compared to those with a primary or lower level of education. Age was positively associated with screening for CC. Furthermore, locational factors, including province and rural-urban residence, were associated with CC screening. Based on these findings, we call for integrated care and management of HIV and non-communicable diseases in Southern Africa, specifically, Zimbabwe due to the legacy of HIV in the region.

Survival outcome and prognostic factors post inadvertent hysterectomy in carcinoma cervix treated with salvage chemo-radiation.

The standard of care for treating early invasive cervical cancer is radical hysterectomy or radiation alone while chemo-radiation is a definitive treatment for advanced disease. Occasionally, a simple hysterectomy is performed in the cancer cervix and these patients merit adjuvant treatment in view of the high chances of loco-regional recurrences. The aim of the study was to analyze the survival outcome of these patients treated with salvage chemo-radiotherapy and also to determine the prognostic factors affecting survival. The medical records of all patients with cervical cancer post simple hysterectomy outside and who received salvage treatment in our department between 2014 and 2020 were retrieved. The data regarding clinical, treatment details and survival were analyzed. A total of 198 patients were included. Median follow-up duration was 45.5months. Gross disease and lymphadenopathy were seen in 60% and 28% patients, respectively. The 5-year progression-free survival(PFS) and overall survival(OS) was 75% and 76%, respectively. Concurrent chemotherapy alone or in combination with induction chemotherapy using three-drug regimens showed better survival compared to those treated by radiation alone. On multivariate analysis, factors found to be adversely affecting OS and PFS were lymph node (LN) size of more than 2cm, non-squamous histology, overall treatment time(OTT) of more than 12weeks and use of non three-drug chemotherapy regimen. Subtotal hysterectomy results in a higher incidence of local recurrence of disease. Factors that impair the outcome in this sub-group of patients are gross lymphadenopathy, non-squamous histology and prolong OTT.

VEGFR2 targeted microbubble-based ultrasound molecular imaging improving the diagnostic sensitivity of microinvasive cervical cancer

BackgroundThe current diagnostic methods of microinvasive cervical cancer lesions are imaging diagnosis and pathological evaluation. Pathological evaluation is invasive and imaging approaches are of extremely low diagnostic performance. There is a paucity of effective and noninvasive imaging approaches for these extremely early cervical cancer during clinical practice. In recent years, ultrasound molecular imaging (USMI) with vascular endothelial growth factor receptor type 2 (VEGFR2) targeted microbubble (MBVEGFR2) has been reported to improve the early diagnosis rates of breast cancer (including ductal carcinoma in situ), pancreatic cancer and hepatic micrometastases. Herein, we aimed to assess the feasibility of MBVEGFR2-based USMI in extremely early cervical cancer detection to provide an accurate imaging modality for microinvasive cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) Stage IA1 and IA2).ResultsWe found MBVEGFR2-based USMI could successfully distinguish extremely early lesions in diameter < 3 mm from surrounding normal tissues (all P < 0.05), and the sensitivity gradually decreased along with increasing tumor diameter. Moreover, normalized intensity difference (NID) values showed a good linear correlation with microvessel density (MVD) (R2 = 0.75). In addition, all tumors could not be identified from surrounding muscles in subtracted ultrasound images when mice were administered MBCon.ConclusionsOverall, MBVEGFR2-based USMI has huge potential for clinical application for the early detection of microinvasive cervical cancer (FIGO Stage IA1 and IA2), providing the foothold for future studies on the imaging screening of this patient population.

Morbidity of adjuvant treatment in early cervical cancer: a retrospective cohort study in a Latin American center.

Radical hysterectomy with pelvic lymph node assessment is the standard of treatment in early cervical cancer. Adjuvant radiotherapy or chemoradiotherapy are offered to patients with risk factors for recurrence. The objective of this study was to compare the incidence of severe (> G3) early or late morbidity related to treatment in patients with cervical cancer undergoing radical surgery with/without adjuvant treatment in a Latin American center. Retrospective cohort study of patients diagnosed with cervical cancer stage IA1 to IB1. Complications were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The cumulative incidence of severe morbidity was estimated. Risk ratios (RR) were calculated to determine the factors associated with morbidity. 239 patients were included. 133 (55.6%) received only radical surgical management and 106 (44.4%) adjuvant treatment. The incidence of early morbidity was 18.8% [95% confidence interval (CI): 12.6% to 26.5%] in the group without adjuvant treatment versus 21.7% (95% CI: 14.3% to 30.8%) in the adjuvant treatment group (p = 0.58). Late morbidity was 3% (95% CI: 1% to 7.5%) and 8.5% (95% CI: 4% to 15.5%), respectively (p = 0.063). No statistically significant differences regarding grade ≥ 3 morbidity between the groups was found (2.3% vs. 5.7%, p = 0.289). Complications during surgery is the only factor associated with postoperative morbidity related to treatment (RR = 4.1) (95% CI: 3% to 5.7%). In our study, the addition of adjuvant treatment for early cervical cancer patients who underwent radical surgery did not increase the incidence of severe early or late morbidity.

Retracted: Application of MRI and CT Images in Surgical Treatment of Early Cervical Cancer.

[This retracts the article DOI: 10.1155/2022/1592449.].

Effect of modified radical laparoscopic hysterectomy versus open radical hysterectomy on short-term clinical outcomes in early-stage cervical cancer: a single-center, prospective, randomized controlled trial

BackgroundThe long-term prognosis of minimally invasive surgery and open surgery for early cervical cancer is controversial. This study mainly discusses the feasibility and effectiveness of the endocutter in radical laparoscopic hysterectomy for early cervical cancer.MethodsA single-center, prospective, randomized controlled trial of modified radical laparoscopic hysterectomy on patients with FIGO stage IA1 (lymphovascular invasion), IA2, and IB1 cervical cancer, between January 2020 and July 2021. Patients were randomly assigned into laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) groups. The ORH group used right-angle sealing forceps for vaginal stump closure, whereas the LRH group used endoscopic staplers. The primary outcomes included the evaluation of the patient’s perioperative indicators, as well as short- and long-term complications. Recurrence and overall survival were considered secondary outcomes.ResultsAs of July 2021, 17 patients were enrolled in the laparoscopic surgery group and 17 in the open surgery group. The hospitalization time of the laparoscopic group was significantly shorter than those of the open group (15 min vs. 9 min, P < 0.001). The vaginal stump closure time in the laparoscopic group was longer than that in the open surgery group, and the difference was statistically significant (P < 0.001). Post-operative catheter removal (P = 0.72), drainage tube removal time (P = 0.27), number of lymph node dissections (P = 0.72), and incidence of intraoperative and post-operative complications between the two groups (P > 0.05). The median blood loss in the laparoscopic group was 278 ml, and it was 350 ml in the laparotomy group. The intraoperative blood transfusion rate was lower in the laparoscopic group; however, these differences did not reach statistical significance (P = 0.175). Vaginal margin pathology and peritoneal lavage cytology were negative, and all the patient’s vaginal stumps healed without infection. The median follow-up time of the laparoscopic group was 20.5 months, and it was 22 months for the open surgery group. There was no recurrence in all patients during the follow-up period.ConclusionsModified LRH with endocutter closure of the vaginal stump is an effective approach and not inferior to ORH in treating patients with early-stage cervical cancer.Trial registrationChiCTR2000030160, date of registration February 26, 2020 (https://www.chictr.org.cn/showprojen.aspx?proj=49809).

Risk factors for lymph node metastasis and clinical outcomes in cervical cancer patients following primary radical hysterectomy: A single-center analysis of 1495 patients.

e17525 Background: Histopathological information obtained from surgical specimen is important to identify patients at increased risk for disease relapse and mortality. Lymph node metastasis (LNM) carries the highest impact on decreased survival in suspected early-stage cervical cancer. To further identify risk factors for LNM and prognosis in early stage cervical cancer patients is definitely necessary owing to the findings from different centers are inconsistent. Methods: A total 1495 cervical cancer patients were diagnosed with stage IA2-IIA cervical cancer according to clinical stage and underwent radical hysterectomy between April 2009 and December 2020. The stage of all the patients were reclassified after surgery according to FIGO 2018. We analyzed their clinicopathologic data to identify the risk factors for LNM. Among all the patients, the progression-free survival (PFS) and overall survival (OS) of 1109 patients between 2015 and 2020 were collected and analyzed. Results: The incidence of LNM is 18.8% in all 1495 patients, which increases with depth of cervical stromal invasion, tumor size, lymphovascular space involvement (LVSI) and vaginal wall invasion in univariate analysis. Multivariable analysis shows only stromal invasion (OR, 3.0; 95% CI, 1.7–5.3; P &lt; 0.001) and LVSI (OR, 4.9; 95% CI, 3.6-6.7; P&lt;0.001) are to be independent risk factors for LNM. In addition, the clinical parameters age is a protective factor against LNM in both univariate and multivariable analysis(P&lt;0.001). Among the 1109 patients, the median follow-up time is 49.7 months. Multivariate analyses using the Cox proportional hazards model show that LNM (HR, 8.5; 95% CI, 3.0-23.9; P&lt;0.001), stromal invasion (HR, 3.4; 95% CI, 2.2-5.4;P&lt;0.001) and special histologic type (HR, 3.2; 95% CI, 1.4-7.6; P=0.006) are independent prognostic factors for OS as well as PFS in early stage cervical cancer. Conclusions: The pattern of cervical stromal invasion and presence LVSI, but not the primary tumor size, predict risk of nodal metastasis. Cervical stromal invasion, LNM and special histologic type (non-squamous cell carcinoma; non-Adenocarcinoma) are independent prognostic factors for OS as well as PFS in early stage cervical cancer. [Table: see text]

Incidence of low volume metastases after retrospective ultrastaging of patients with early stage, node negative cervical cancer and receipt of post-operative adjuvant therapy.

e17506 Background: Nodal positivity directs receipt of adjuvant post-operative therapy in early stage cervical cancer; the significance of low-volume metastases (LVM) is unclear. We hypothesized patients with early stage cervical cancer with high risk factors on pathology and negative nodes would have a higher incidence of LVM on retrospective ultrastaging. Methods: This retrospective cohort study collected clinicopathologic data via chart review on early stage cervical cancer patients treated at our institution from January 2011 - June 2021. The study was approved by the IRB. Inclusion criteria included patients &gt;18 years old who underwent a radical hysterectomy/trachelectomy with pathology-proven negative nodes who went on to be recommended for post-operative adjuvant therapy, due to factors defined under Sedlis or Peters criteria. Patients were excluded for rare histology or prior pelvic radiation. Resected nodes were ultrastaged, performed by 4 re-cuts at 20 microns on each lymph node staging, stained with H&amp;E and one level with CK AE1/AE3 to identify presence of any LVM. Analysis was performed via descriptive statistics with Microsoft Excel. Results: 199 patients were treated with radical hysterectomy between 2011-2021; 20 met study criteria. The average age at diagnosis was 51 years: 65% Caucasian, 25% Black, 10% Latino. 75% had Squamous cell carcinoma, 85% (n=17) of the cohort were a 2009 FIGO pathologic Stage 1B. 35% of the cohort underwent a minimally invasive hysterectomy. Tumor size varied: 25% (n=5) of tumors were less than 2 cm, 35% (n=7) of tumors measured greater than or equal to 2 cm, 30% (n=6) measured greater than or equal to 3 cm, and 10% (n=2) measured greater than or equal to 4 cm. Lymphovascular space invasion was noted in 75% (n=15) of samples. Superficial stromal invasion was noted in 5% (n=1), deep stromal invasion was noted in 65% (n=13). 5% (n=1) of patients had parametrial invasion, and 5% (n=1) had positive margins. A full bilateral pelvic lymphadenectomy was performed on every patient, with 245 nodal blocks ultrastaged. 80% (n=16) received adjuvant therapy: 3 chemoradiation, 13 radiation, 4 declined. LVM was identified in 5% (n=1) patients; a macrometastases was identified as missed in the initial pathologic evaluation of another. 10% (n=2) patients developed recurrence, one at the pelvic brim and one distant (lung). The patient with the newly identified LVM received adjuvant radiation, and developed recurrence at the pelvic brim. Conclusions: The results of this small study suggest traditional “high risk” factors in surgically managed cervical cancer is associated with positive ultrastaged nodes in 5% of cases. This finding suggests that utilization of sentinel node identification with associated ultrastaging will accurately identify patients who will benefit from adjuvant therapy.

Tertiary lymphoid structure prevalence and prognostic value in cervical cancer.

e17521 Background: Recurrent or progressive cervical cancer have limited second-line treatment options. Response rates are often poor to second-line therapy (average response rate of 15%). Identification of factors which predict response to immunotherapy and targets to enhance the immune response are critically needed in cervical cancer. Chronic inflammation can initiate an immune response in non-secondary lymphoid organs (SLO) and form a Tertiary Lymphoid Structure (TLS). TLS is composed of immune cells clustered and organized and responsible for immune cell chemotaxis, which impacts cancer therapeutic response. Chemokine ligand 13 (CXCL13) is related to B cell attraction and TLS formation. Recent work from our group demonstrated human papilloma virus (HPV) positive head and neck squamous cell carcinoma (HNSCC) exhibited greater tumor infiltrating B cells (TIL-Bs) and TLS vs HPV negative disease indicating a role for viral infection in immune infiltration. Most cervical cancer is caused by HPV infection, therefore we investigated prognostic significance of immune infiltration in cervix cancer. Methods: A cohort analysis was conducted on 43 patients diagnosed with early stage cervical cancer. The presence of B cells, CD8 T cells, and CXCL13 was analyzed using singleplex immunohistochemistry staining. We separated infiltration into high infiltration and low infiltration, defined by their median value. TLS was identified using a multiplex immunofluorescence for TLS maturity panel. Histological findings were associated with cohort data. Results: High intratumoral infiltration of CD8 T cells was associated with longer overall survival in cancer patients. Median survival was 45 months for low infiltration group, whereas it was not reached by higher T cell infiltration (p &lt; 0.05). The prognostic value of T cell infiltration was stronger in adenocarcinoma, typically associated with worse outcomes, than in squamous cell carcinoma. In adenocarcinoma, median survival was 58 months for low T cell infiltration, it was not reached by high infiltration group. CXCL13 levels were prognostic for recurrence-free survival, with median survival of 53 months in low expression group and not reached in high CXCL13 presence group (p &lt; 0.05). The presence of TLS compared to low B cell infiltration was associated to higher survival, with 0% of deaths in the TLS group vs 40% in low B cell infiltration. While there was no correlation between TIL-B and patient outcomes, the presence of B cells in the aggregation process and higher CXCL13 levels were associated with improved survival, with 9% deaths vs 36% in low B cell group, possibly due to the support of TLS formation by B cell aggregation surrounded by CXCL13. Conclusions: Our study suggests that the presence of TLS, whether forming or established, is linked to improved clinical outcomes in cervical cancer. Further research is necessary to investigate the response of this cancer type to immunotherapy.

Impact of hospital volume and margin status on survival following radical hysterectomy: An expanded NCDB study.

e17527 Background: Use of a minimally invasive surgical (MIS) approach to manage early-stage cervical cancer has been previously associated with an elevated risk of disease recurrence and death. However, the reasons why MIS would lead to worse clinical outcomes remains unclear. Here, we sought to determine whether hospital surgical volume and surgical margin status contribute to worse outcomes previously reported for minimally invasive radical hysterectomy (RH-MIS). Methods: Demographic and outcome data for women diagnosed with an invasive carcinoma of the cervix (SCCa) between 2010 and 2015 were abstracted from the National Cancer Database (NCDB). Differences by surgery type were examined using chi-square test for categorical variables and independent samples t-test test for continuous variables. Surgical margin status was reported as either positive or negative according to the presence of malignancy. Overall survival was evaluated using the Kaplan-Meier method and multivariable Cox proportional hazards regression. Analyses were stratified by hospital volume. Low volume facilities were defined as institutions performing &lt;10 surgeries per year. Results: We identified a total of 5,090 women who underwent radical hysterectomy by either minimally invasive (n=2181) or open (n=2909) approach. Between 2010 and 2015, the proportion of radical hysterectomies performed by RH-MIS increased from 42.7% to 70.3% of all cases. In contrast to prior reports, 5-year survival among RH-MIS patients was significantly better compared to RH-open patients (92.5% vs. 90.8%, p=0.02). However, women who underwent RH-MIS were significant younger (45.6±12.3 v. 46.8±12.3 years, p&lt;0.001), more educated (p&lt;0.001), more likely to be White Non-Hispanic (p&lt;0.001) and diagnosed with earlier stage disease (p&lt;0.008). Women who underwent RH-MIS were also less likely to have positive surgical margins (2.2% v 3.5%, p=0.006). After accounting for these differences, there was no statistically significant difference in survival for women undergoing RH-MIS vs. RH-open (HR, 1.18; 95% CI: (0.96-1.45). Positive margin status was associated with worse survival only at low-volume hospitals (HR, 2.30; 95% CI: 1.09-11.31). However, no other association between hospital volume, surgical route, margin status and survival was observed. Curiously, survival for women diagnosed in 2012 (HR, 1.51; 95% CI, 1.05 – 2.17) and 2013 (HR, 1.49; 95% CI, 1.03-2.15) not other years was significantly worse when compared to 2015, regardless of surgical route. Conclusions: Positive surgical margins following radical hysterectomy appear to be most effectively addressed at high volume centers caring for women with cervical cancer. These observations underscore a national need for equitable access to radiation care for women being treated for early stage cervical cancer.

Erken Evre Serviks Kanserinde Sedlis Kriterleri Gözönünde Bulundurularak Uygulanan Adjuvant Radyoterapi Sonuçları

Background/Aims:&#x0D; Investigation of the efficacy of adjuvant RT in cervical cancer stage I-IIA according to FIGO (2018) in terms of risk factors and oncologic outcomes.&#x0D; Methods: &#x0D; The study included 113 patients with FIGO stage I-IIA. Patients who received adjuvant external pelvic RT and/or intracavitary brachytherapy (ICBT) after surgery retrospectively analyzed for demographic data , histology, grade, tumor size , stage, LVSI, stromal invasion depth, type of lymphadenectomy, number of dissected pelvic / paraaortic lymph nodes , surgical margin, adjuvant therapies, local relapse, distant failure, overall survival, and progression-free survival.&#x0D; Results:&#x0D; After a median follow-up of 160 months, local recurrence was observed in 3 patients, distant metastasis in 6 patients and all-cause death in 15 patients. It was observed that only SID had a statistically significant effect on overall survival among the Sedlis criteria (p=0.04). The ten-year DFS and OS rates were 95% and 94%, respectively .&#x0D; Conclusions:&#x0D; Promising oncological results were obtained in early stage cervical cancer with adjuvant RT based on Sedlis criteria.

Survival outcomes of laparoscopic versus open radical hysterectomy in early cervical cancer with incidentally identified high-risk factors

ObjectivePreviously, we suggested that patients with cervical cancer (CC) with tumors ≤2 cm on preoperative magnetic resonance imaging (MRI) are safe candidates for laparoscopic radical hysterectomy (LRH). Here, we aim to investigate whether LRH deteriorates the prognosis of patients with incidentally identified high-risk factors; lymph node metastasis (LNM) or parametrial invasion (PMI). MethodsWe identified patients with 2009 FIGO stage IB1 CC who underwent Type C LRH or open radical hysterectomy (ORH) at three tertiary hospitals between 2000 and 2019. Those with a tumor ≤2 cm on preoperative MRI who were not suspicious of LNM or PMI preoperatively were included, while those who were indicated to receive adjuvant treatment but did not actually receive it were excluded. Survival outcomes were compared between the LRH and ORH groups in the overall population, then narrowed down to those with LNM, and then to those with PMI. ResultsIn total, 498 patients were included: 299 in the LRH group and 199 in the ORH group. The LRH and ORH groups showed similar 3-year progression-free survival (PFS) (94.0% vs. 93.6%; P = 0.615) and 5-year overall survival (OS) rates (97.2% vs. 96.8%; P = 0.439). On pathologic examination, 49 (9.8%) and 16 (3.2%) patients had LNM and PMI, respectively, and 10 (2.0%) had both. In the LNM subgroup, 5-year PFS rate was not significantly different between the LRH and ORH groups (73.2% vs. 91.7%; P = 0.169). In the PMI subgroup, no difference in PFS was observed between the two groups (P = 0.893). ConclusionsLRH might not deteriorate recurrence and mortality rates in CC patients with tumors ≤2 cm when adjuvant treatment is appropriately administered, even if pathologic LNM and PMI are incidentally identified.

The incidence of perioperative lymphatic complications after radical hysterectomy and pelvic lymphadenectomy between robotic and laparoscopic approach : a systemic review and meta-analysis.

Although many studies have reported perioperative complications after radical hysterectomy and pelvic lymph node dissection using robotic and laparoscopic approaches, the risk of perioperative lymphatic complications has not been well identified. The aim of this meta-analysis is to compare the risks of perioperative lymphatic complications after robotic radical hysterectomy and lymph node dissection (RRHND) with laparoscopic radical hysterectomy and lymph node dissection (LRHND) for early uterine cervical cancer. The authors searched the PubMed, Cochrane Library, Web of Science, ScienceDirect, and Google Scholar databases for studies published up to July 2022 comparing perioperative lymphatic complications after RRHND and LRHND while treating early uterine cervical cancer. Related articles and bibliographies of relevant studies were also checked. Two reviewers independently performed the data extraction. A total of 19 eligible clinical trials (15 retrospective studies and 4 prospective studies) comprising 3079 patients were included in this analysis. Only 107 patients (3.48%) had perioperative lymphatic complications, of which the most common was lymphedema ( n =57, 1.85%), followed by symptomatic lymphocele ( n =30, 0.97%), and lymphorrhea ( n =15, 0.49%). When all studies were pooled, the odds ratio for the risk of any lymphatic complication after RRHND compared with LRHND was 1.27 (95% CI: 0.86-1.89; P =0.230). In the subgroup analysis, study quality, country of research, and publication year were not associated with perioperative lymphatic complications. A meta-analysis of the available current literature suggests that RRHND is not superior to LRHND in terms of perioperative lymphatic complications.

Parameters of free radical oxidation and antioxidant defense in patients with cervical cancer before and after radical surgical treatment

Purpose of the study. To analyse free radical oxidation and antioxidant defense in patients diagnosed with early cervical cancer (CC) before and after radical surgical treatment.Patients and methods. Levels of diene conjugates, malondialdehyde (MDA), superoxide dismutase (SOD), catalase, glutathione, glutathione- dependent enzymes, vitamins A and E were determined in 74 women under the age of 45 (48 patients those who were at the stage of surgical treatment with a diagnosis of CC at the National Medical Research Center of Oncology in the period 2017–2020 and 26 healthy women).Results. Patients with early CC showed significant changes in the intensity of lipid peroxidation processes and in antioxidant defense: elevate levels of MDA and diene conjugates, initial decline in the activity of SOD and catalase, low levels of vitamins A and E. These results complete the understanding of the processes occurring in the body of an oncological patient at the initial stage of tumor formation, which does not yet have an obvious clinical manifestation. After total removal of the ovaries, most of the indicators characterizing the enzymatic link of the antioxidant system tend to normalize, while the violation of the content of vitamins E and A (related to the non-enzymatic link of the antioxidant system) worsens.Conclusions. Desynchronization of free radical oxidation processes with multidirectional changes in oxidation and antioxidation in patients with early CC at the stage of radical surgical treatment should be considered from the position of hormone‑ reducing surgery and a resulting complex of changes in the organs and systems of women with cancer.

Circulating HPV DNA as a Biomarker for Pre-Invasive and Early Invasive Cervical Cancer: A Feasibility Study.

High-risk HPV infection is responsible for >99% of cervix cancers (CC). In persistent infections that lead to cancer, the tumour breaches the basement membrane, releasing HPV-DNA into the bloodstream (cHPV-DNA). A next-generation sequencing assay (NGS) for detection of plasma HPV circulating DNA (cHPV-DNA) has demonstrated high sensitivity and specificity in patients with locally advanced cervix cancers. We hypothesised that cHPV-DNA is detectable in early invasive cervical cancers but not in pre-invasive lesions (CIN). Blood samples were collected from patients with CIN (n = 52) and FIGO stage 1A-1B CC (n = 12) prior to treatment and at follow-up. DNA extraction from plasma, followed by NGS, was used for the detection of cHPV-DNA. None of the patients with pre-invasive lesions were positive for CHPV-DNA. In invasive tumours, plasma from one patient (10%) reached the threshold of positivity for cHPV-DNA in plasma. Low detection of cHPV-DNA in early CC may be explained by small tumour size, poorer access to lymphatics and circulation, and therefore little shedding of cHPV-DNA in plasma at detectable levels. The detection rate of cHPV-DNA in patients with early invasive cervix cancer using even the most sensitive of currently available technologies lacks adequate sensitivity for clinical utility.

Increasing trends of cervical conization with lymph node evaluation for fertility-sparing surgery in early cervical cancer

ObjectiveTo examine uptake, characteristics, and survival outcome of less-radical fertility-sparing surgery with cervical conization and lymph node evaluation (Cone-LN) in reproductive age patients with early cervical cancer. MethodsThis retrospective cohort study examined the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population included 407 patients aged <50 years with stage IA-IB2 (≤4 cm) cervical cancer who received fertility-sparing surgery from 2004 to 2019. The exposure was fertility-sparing surgery type: Cone-LN (n = 196) or trachelectomy with lymph node evaluation (Trach-LN, n = 211). The main co-outcomes were (i) temporal trends of surgery type, assessed with Cochran-Armitage test, and (ii) clinical and tumor characteristics, assessed with multivariable binary logistic regression model. The secondary outcome was overall survival, assessed with inverse probability of treatment weighting propensity score. ResultsThe number of patients receiving Cone-LN increased from 43.5% in 2004–2007 to 58.4% in 2016–2019 (P-trend = 0.005). Patients receiving conization and sentinel lymph node (SLN) biopsy alone increased from 0% to 14.4% (P-trend < 0.001). In a multivariable analysis, patients in the Cone-LN group were more likely to undergo SLN biopsy (aOR 6.04) compared to those in the Trach-LN group whereas those with adenocarcinoma (aOR 0.49) and T1b tumors (aOR for ≤2 cm 0.21, and aOR for 2.1–4.0 cm 0.10) were less likely to receive Cone-LN. In a propensity score-weighted model, the Cone-LN and Trach-LN groups had comparable overall survival (7-year rates, 98.9% vs 97.8%). Similar associations were observed for patients with squamous, adenocarcinoma / adenosquamous, T1a classification, and T1b(≤2 cm) classification. ConclusionThe current population-based analysis suggests that the performance of cervical conization with lymph node evaluation, particularly with SLN biopsy, is gradually increasing for early cervical cancer patients desiring future fertility.

The Role of Graphene Oxide in the Inhibition of Migration and Invasion of Cancer Cells by Destroying Actin Cytoskeleton and via Inhibiting the Activities of ETC Complexes

Abstract: Cancer is one of the most important threats to public health. Cancer is characterized by cell proliferation that has eluded central endogenous control mechanisms. Cervical cancer is the third most common cancer among women, followed by skin cancer and breast cancer, the first and second most common causes, respectively. In developing countries, cervical cancer is usually the most common cancer in women and may account for 25% of all female cancers. Over the years, the diagnosis and treatment of cervical cancer have made rapid progress, resulting in a decline in the mortality and morbidity of the disease. Unfortunately, although surgery and radiotherapy have effective treatment options for early cervical cancer, poor prognosis is still a challenge in the treatment of metastatic cervical cancer. Therefore, it is very important to reveal the mechanism of cervical cancer and explore new therapies against tumor invasiveness. At present, it is reported that nanomaterials are used in the detection and treatment of various types of malignant tumors due to their different targeting effects in many fields, such as imaging, immune detection, chemotherapy, radiotherapy and immunotherapy. The cytotoxicity and inhibitory effects of graphene oxide (GO) on tumor invasion and metastasis were studied in recent studies using the human cervical cancer Hela cell line, as well as the probable mechanisms and signaling pathways involved. Here we collect the last reports, with focus on the role of GO in the inhibition of migration and invasion of cancer cells with the goal of exposing possible potential pathways to provide new insights for specific treatment of cancer.