Invasive Cervical Cancer Patients Research Articles

Overexpression of Hypermethylated Homeobox A11 (HOXA11) Inhibits Tumor Cell Growth and Induces Apoptosis in Cervical Cancer.

This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a therapeutic target and a diagnostic methylation marker for cervical cancer. Gene expression analysis using cDNA microarray in cervical cancer cell lines revealed significantly reduced expression of the HOXA11 gene. Subsequent investigation of HOXA11 promoter methylation in samples from normal individuals and invasive cervical cancer patients showed over 53.2% higher methylation in cancer scrapes compared to normal scrapes. Furthermore, overexpression of HOXA11, which is downregulated in cervical cancer, strongly suppressed cell growth in cervical cancer cell lines, HeLa and HT3. Additionally, we performed transferase dUTP nick end labeling assay and confirmed that the inhibition of cervical cancer cell proliferation occurred via apoptosis. Mechanistically, overexpression of HOXA11 led to mitochondrial apoptosis characterized by PARP cleavage due to increased c-Myc and enhanced cytochrome C secretion into the cytoplasm. These findings suggest that HOXA11 could potentially serve as a methylation marker for diagnosing cervical cancer and as a novel therapeutic target for its treatment.

Exploring the diversity of vaginal microbiota between healthy women and cervical cancer patients in India.

Introduction. Cervicovaginal diversity has been reported as a predictive biomarker for cervical cancer risk. We recently reported the bio-therapeutic potential of vaginal probiotics from healthy Indian women against vaginal pathogens, isolated from the invasive cervical cancer (ICC) patients.Gap Statement. The cervicovaginal microflora from cervical cancer patients has not yet been reported from Indian population.Aim. The present study aimed at comparing the cervicovaginal microbiome between healthy controls (HC) and ICC patients from the Indian population.Methodology. In total, 30 vaginal swabs (15 from HC and 15 from ICC) were subjected to 16S rRNA gene sequencing. Alpha diversity was evaluated by Shannon and Chao1 index; and beta diversity by principle coordinate analysis (PCoA) of weighted and unweighted UniFrac distances. The relative abundance of the microbial taxa was done according to linear discriminant analysis effect size (LEfSe).Results. Predominance of Staphylococcus spp. in ICC and Lactobacillus gasseri in HC groups was observed. Alpha-diversity was found to be higher in ICC as compared to HC but was statistically non-significant. LEfSe analysis revealed Bacteroides fragilis and Escherichia coli as the marker genera in ICC with a marked decrease in Lactobacillus sp. Contrarily, in HC, L. gasseri, L. iners and L. fermentum were found to be abundant.Conclusion. Differences in the vaginal microbiome between healthy and ICC women could help in the early prediction of cervical cancer risk and thus in designing prevention strategies.

Stage and outcomes of invasive cervical cancer patients in Botswana: A prospective cohort study from 2013 to 2020

ObjectiveTo present the stage distribution, patterns of care, and outcomes of patients from Botswana with invasive cervical cancer, living with or without HIV. MethodsBetween 2013 and 2020, women with cervical cancer were prospectively enrolled in an observational cohort study. ResultsA total of 1,043 patients were enrolled; 69% were women living with HIV. The median age of the cohort was 47 years (interquartile range [IQR] 40–58 years), with women living with HIV presenting at a younger age compared to women without HIV (44 versus 61 years, p < 0.001). Among women living with HIV, the median CD4 count at the time of cancer diagnosis was 429.5 cells/μL (IQR 240–619.5 cells/μL), 13% had a detectable viral load, and 95% were on antiretroviral therapy. In regard to treatment, 6% (n = 58) underwent surgery, 33% (n = 341) received radiation therapy, 51% (n = 531) received chemoradiation, and 7% (n = 76) did not receive treatment. Stage distribution in the cohort was as follows: I 17% (n = 173), II 37% (n = 388), III 35% (n = 368), and IV 8% (n = 88). For all patients, 2-year OS was 67%. In multivariable Cox regression, worse OS was associated with stage: II (HR 1.91, p = 0.007), III (HR 3.99, p < 0.001), and IV (HR 5.06, p < 0.001) compared to stage I. Improved OS was associated with hemoglobin > 10 g/dL (HR 0.51, p < 0.001) compared to Hb ≤ 10 g/dL. ConclusionsAmong women in Botswana with cervical cancer, most patients presented with stage II or III disease warranting radiation therapy or chemoradiation. While two-thirds of cervical cancer patients were women living with HIV, HIV did not impact OS.

Prevalence of high-risk human papillomavirus and cervical lesion risk factors: A population-based study in Zhejiang, China 2010-2019.

This study investigates the epidemiological characteristics of high-risk human papillomavirus (hrHPV) and analyzes the risk of cervical lesions among women in Zhejiang province, China. HPV data were collected retrospectively from a cohort of 67 742 women who underwent routine cervical cancer screening from 2010 to 2019. Precancerous and cervical cancer cases (n = 980) were histologically diagnosed as a low-grade squamous intraepithelial lesion (LSIL; n = 341) or a high-grade squamous intraepithelial lesion (HSIL; n = 499) and invasive cervical cancer (ICC) (n = 140) groups. Disordered logistic regression analysis was used to test the relationship between different degrees of cervical lesions, HPV16/18 infection status, positive rate of p16INK4a (p16), Ki-67 expression, and patient's age in SIL and ICC (270/980 cases) patients. HPV52 (4.7%) was the most prevalent HPV type, followed by HPV16 (3.3%) and HPV58 (2.6%). HPV16 was the most common HPV in SIL, peaking at the age of 30-39. The HPV16 infection rate was significantly higher in HSIL than in LSIL patients; moreover, HPV16, HPV18, and HPV51 infection rates were significantly higher in ICC patients than in HSIL (Bonferroni-adjusted p < 0.0167). The presence of HPV16/18 was also associated with a higher risk of developing HSILfrom LSIL(odds ratio [OR] = 9.198, 95% confidence interval [CI]: 2.76-127.49). The increased p16 expression and HPV16/18 were associated with the increased risk of cancer progression (OR = 1.092, 95% CI: 1.03-1.36; OR = 1.495, 95% CI: 1.23-2.19, respectively). The identified hrHPV genotypes in cervical lesions can serve as a baseline indicator for future vaccine assessment in Zhejiang, China.

Up-regulation of peroxiredoxin 3 by high-risk human papillomavirus in cervical cancer cells

IntroductionPeroxiredoxin 3 (PRX3) is a member of PRX family with antioxidant functions by scavenging hydrogen peroxide. Since the development of cervical cancer is causally linked to high-risk human papillomavirus (HPV) that induces oxidative stress, we conducted the present study to investigate the response of PRX3 to high-risk HPV infection.Material and methodsThis study included fifty-six patients with invasive squamous cervical cancer and sixty control patients with hysteromyoma. Enzyme-linked immunosorbent assay was performed to detect cervical oxidative stress and serum PRX3. The expression of PRX3 and oncoprotein E6 of HPV16 or HPV18 was examined in cervical cancer tissues by immunohistochemistry. Western Blot was applied to detect the expression of PRX3 and E6 in cervical cancer cell lines including CaSki, HeLa, and C33A.ResultsPatients with cervical cancer showed higher serum PRX3 than control patients with hysteromyoma. Levels of oxidative markers in cervical cancer tissues were elevated as compared to normal cervical epithelia. PRX3 expression was upregulated in cervical cancer tissues and the upregulation was positively associated with the expression of E6 of HPV16 or HPV18. The association was confirmed in HPV-containing cervical cancer cell lines including CaSki and HeLa.ConclusionsOur results indicated a positive response of PRX3 to HPV-induced oxidative stress. Serum PRX3 might be a potential indicator of active amplification of high-risk HPV in cervical cancer cells.

Renal function impairment in cervical cancer patients treated with cisplatin-based chemoradiation: A review of medical records in a Zimbabwean outpatient department.

There is a potential increase in risk of renal function impairment among patients with invasive cervical cancer (ICC) who are HIV-positive and treated with cisplatin-based concurrent chemoradiation (CCRT). This concern is due to overlapping nephrotoxicity of the drugs, and nephropathy from the diseases themselves. There is limited literature available for the short-term renal outcomes for HIV-positive patients with ICC during routine clinical management. This study aimed to assess if HIV-infection increased the risk of renal impairment in ICC patients treated with CCRT, and explore the respective risk factors. This was a retrospective review of records of ICC patients treated with at least one cycle of weekly cisplatin during CCRT at the Parirenyatwa Radiotherapy Center from January 2017-December 2018. The RIFLE criteria were used to classify renal impairment. Analyses were performed with Fisher's Exact tests, Wilcoxon rank sum tests. Odds ratios (OR) were generated using logistic regression. All statistical tests were 2-sided at a 5% level of significance. Seventy-two eligible patients were identified, 32 (44.44%) were HIV-positive. HIV-positive patients were younger (p = 0.002), had lower albumin levels (p = 0.014) and received lower cisplatin doses (p = 0.044). The mean percent reduction in estimated glomerular filtration rate (eGFR) from baseline was -19% (95% CI: -25.9% to -13.2%) for all patients. Thirty-one (43.1%) patients experienced renal impairment, 50% and 37.5% of HIV-positive and -negative patients respectively (p = 0.287). HIV-infection was associated with an adjusted OR of 1.16 (95% CI 0.35-3.43, p = 0.769). Baseline eGFR< 60ml/min was the only independent predictor of renal impairment, OR 0.25 (95% CI: 0.07-0.85). Baseline eGFR<60ml/min was also associated with receipt of lower cisplatin doses (p = 0.044). HIV-infection was not associated with elevated risk of renal impairment. Patients with an eGFR<60ml/min appear to be managed more cautiously reducing their risk for renal impairment during cisplatin therapy. The high prevalence of renal impairment in this population suggests the need for optimization of pre-treatment protocols.

A phase III randomised trial of trans-abdominal ultrasound in improving application quality and dosimetry of intra-cavitary brachytherapy in locally advanced cervical cancer

IntroductionIntra-cavitary brachytherapy (ICB) remains an integral part of radiotherapy treatment in cervical cancer. Two-dimensional X ray point-based planning remains common and blind insertion leads to uterine perforations and higher toxicity. We conducted a randomised controlled trial of using trans-abdominal ultrasound in performing ICB to reduce perforation and organ at risk doses. Patient and methodsThe present study is a phase III open label randomised controlled trial of ultrasound guided ICB conducted on invasive cervical cancer patients. Patients were randomised by a simple computer-generated randomization chart into Arm A (No Ultrasound guidance) and Arm B (ICB with ultrasound guidance). The uterine perforation rates, tandem length change rates, bladder doses, rectal dose and procedure times were compared. Fischer exact test was used to compare the arms and p value <0.05 considered significant. ResultsA total of 160 patients were randomised. With US assistance, the uterine perforation rate was 1.25% (n = 1). In the non-US assistance arm the perforation rate was 12.5% (n = 10) (p = 0.005). Mean time to complete the entire procedure was significantly shortened from 26 min to 19 min favouring the US arm (p = 0.001). Dosimetric assessment between the two groups showed significant decrease in dose received by the various organs at risk with US assistance. ConclusionThe present study confirms significant improvement in application quality as well as dosimetry with reduction in procedure time. Trans-Abdominal US should be routinely used for ICB procedures, particularly in resource limited settings.

Prevalence of HPV 16/18 Subtypes Among Invasive Cervical Cancer Patients from a Tertiary Care Hospital in South India: A Cross-Sectional Study

To find out the proportion of HPV sub types 16 & 18 in invasive cervical carcinoma. This is a prospective observational study performed on 100 women with invasive cervical cancer. RT PCR was performed on the DNA extracted from the punch biopsy using RNA primers specific for subtypes 16 and 18. The mean age of the population was 53.25 years. The mean age of coitus was 19.25 years. Around 70% of the patients belong to class 4 or above socioeconomic status. The most common presenting symptom was vaginal discharge seen in 40% of the cases. The most common stage was stage IIB (40%) followed by IIIB (22%). 52% of the population had Grade 3 disease. In our study, the proportion of HPV-positive cancer was 64%. 60% of the patients were positive for HPV 16 subtype, and 22% were positive for HPV 18 subtypes. 18% were positive for both HPV 16 and 18. All stage IV A and IV B patients had HPV positivity. Around two-third of the cervical cancer are attributed to high-risk HPV 16 and 18. Bivalent vaccine can reduce a significant proportion of cases in our country.

Outcomes of prior cervical cytology and HR-HPV testing in women subsequently diagnosed with CIN1, CIN2/3, and invasive cervical cancer: a 4-year routine clinical experience after implementation of systematic training and quality control programs

BackgroundIn 2013, Jinan KingMed Diagnostics (JKD) first established a systematic cervical cytology training and quality control (QC) program in Shandong Province, China. We compared the efficacy of high-risk human papillomavirus (HR-HPV) detection, cytology, and their combination in routine clinical practice after the implementation of the training and QC program to identify the optimal first-line screening method in this region.MethodsThe data of patients histologically diagnosed with cervical intraepithelial neoplasia (CIN) 1, CIN2/3, and invasive cervical cancer (ICC) between January 2014 and December 2017 were retrieved from the JKD database. Cytology and/or HR-HPV testing results within 3 months preceding the CIN1 diagnoses and 6 months preceding the CIN2/3 and ICC diagnoses were analyzed.ResultsPrior screening data were available for 1829 CIN1 patients, 2309 CIN2/3 patients, and 680 ICC patients. Cytology alone and HR-HPV testing alone had similar rates of positive results for CIN2/3 (97.2% [854/879] vs. 95.4% [864/906], P = 0.105) and ICC detection (89.1% [205/230] vs. 92.7% [204/220], P = 0.185). Compared with either method alone, co-testing slightly increased the screening sensitivity for CIN2/3 (99.8% [523/524], all P < 0.001) and ICC (99.6% [229/230], all P < 0.001) detection. In the CIN1 group, cervical cytology alone (92.9% [520/560]) was more sensitive than HR-HPV testing alone (79.9% [570/713], P < 0.001), and co-testing (95.3% [530/556]) did not significantly improve the screening sensitivity (P = 0.105).ConclusionsAfter the implementation of a systematic training and QC program, both cytology and HR-HPV testing may be adopted for primary cervical cancer screening in Shandong Province.

Human papillomavirus Posttreatment Clearance Time in Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer.

ObjectiveThe aim of the study was to determine an appropriate follow-up schedule for human papillomavirus (HPV) detection by evaluating the clearance time of HPV after treatment.Materials and MethodsA retrospective study was conducted on 97 high-grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia 2–3) patients and 437 early invasive cervical cancer (CC) (stages Ia–IIa) patients who received radical surgery at the Affiliated Tumor Hospital of Xinjiang Medical University. Patient medical information, including personal information, pathological diagnosis, HPV infection status, and therapeutic methods, was obtained through the hospital's historical medical records management system. The clearance time of HPV was determined using Kaplan-Meier method analysis, and clearance time of HPV among different age groups, different grades, and different clinical stages were compared using the log-rank test.ResultsThe median clearance time of all patients was 10.4 months. The median clearance time was longer in HSIL patients than in early invasive CC patients (p < .05). No statistical significance was found among different HSIL grades, CC stages, or patient age groups (P > 0.05).ConclusionsDelaying first posttreatment follow-up to 9 months in patients at high risk of noncompliance could potentially reduce burden of cost and repeated clinical visits. This follow-up approach could be consistently applied to all women regardless of age, severity, and extent of disease.

Low-Risk Human Papillomavirus Types in Cervical Intraepithelial Neoplasia 2-3 and in Invasive Cervical Cancer Patients.

A total of 95% to 99% of patients with invasive cervical cancer (CC) are infected with human papillomavirus (HPV). The aim of the study was to evaluate the incidence of low-risk HPV (LR-HPV) types among women with cervical intraepithelial neoplasia (CIN 2-3) and CC. We conducted a nested cohort study of patients diagnosed with CIN 2-3 or CC. Inclusion criteria were diagnosis of CIN 2-3 or CC and HPV-DNA testing from the cervix. During the study period, we collected clinical data on 608 women of whom 402 were with CIN 2-3 and 206 with diagnosis of CC. When examining 14 high-risk HPV (HR-HPV) types, patients with CIN 2-3, 90.3% were found positive to at least one type of HR-HPV, 89.8% from CC patients were found positive to at least one type of HR-HPV. A total of 4.5% of patients with CIN 2-3 and 3.9% of those with CC were positive to only one LR-HPV or to some of a few LR-HPV types. Among 5.2% with CIN 2-3 and 6.3% of those with CC, no HPV types were detected. The prevalence of the LR-HPV in high-grade squamous intraepithelial lesion cervical lesions is low but is expected to increase in the future because of the expected decrease in CC caused by HPV types that are included in the bi-, quadri-, and nanovalent vaccine. The CIN 2-3 and CC patients with LR-HPV types and with negative HPV, challenge HPV screening sensitivity, which is based on a limited number of HR-HPV types.

Identification and validation of a prognostic proteomic signature for cervical cancer

ObjectiveTo date, The Cancer Genome Atlas (TCGA) has provided the most extensive molecular characterization of invasive cervical cancer (ICC). Analysis of reverse phase protein array (RPPA) data from TCGA samples showed that cervical cancers could be stratified into 3 clusters exhibiting significant differences in survival outcome: hormone, EMT, and PI3K/AKT. The goals of the current study were to: 1) validate the TCGA RPPA results in an independent cohort of ICC patients and 2) to develop and validate an algorithm encompassing a small antibody set for clinical utility. MethodsSubjects consisted of 2 ICC patient cohorts with accompanying RPPA and clinical-pathologic data: 155 samples from TCGA (TCGA-155) and 61 additional, unique samples (MCW-61). Using data from 173 common RPPA antibodies, we replicated Silhouette clustering analysis in both ICC cohorts. Further, an index score for each patient was calculated from the survival-associated antibodies (SAAs) identified using Random survival forests (RSF) and the Cox proportional hazard regression model. Kaplan-Meier survival analysis and the log-rank test were performed to assess and compare cluster or risk group survival outcome. ResultsIn addition to validating the prognostic ability of the proteomic clusters reported by TCGA, we developed an algorithm based on 22 unique antibodies (SAAs) that stratified women with ICC into low-, medium-, or high-risk survival groups. ConclusionsWe provide a signature of 22 antibodies which accurately predicted survival outcome in 2 separate groups of ICC patients. Future studies examining these candidate biomarkers in additional ICC cohorts is warranted to fully determine their clinical potential.

Deregulation of miR-21 and miR-29a in Cervical Cancer Related to HPV Infection.

Early diagnosis is an important factor to improve the survival of Invasive Cervical Cancer (ICC) patients. Molecular biomarkers such as micro RNA (miRNA) can be used in the early detection of ICC. The expression of miR-21 and miR-29a are deregulated in many types of human cancers. The aim of this study was to investigate the differences in miR-21 and miR-29a expression patterns in the Human Papilloma Virus (HPV) infection and various grades of cervical cancer among Iranian women. Small RNAs were extracted from positive for HPV, cervical cancer and healthy samples from 43, 50 and 46 individuals, respectively. Expression levels of miR-21 and miR-29a were analyzed by SYBR Green real-time RT-PCR using specific primers, and 5s rRNA as the internal reference gene. Results have shown a significant increase in miR-21 and decrease in miR-29 in cancerous samples in comparison with the control groups (P < 0.0001). This study illustrated that miR-21 and miR-29a could be operated as an oncogene and tumor-suppressor in cervical cancer progression. More studies are needed to demonstrate the role of miR-21 and miR-29a as potential biomarkers for the diagnosis of cervical cancer in future investigations.

INVASIVE CERVICAL CANCER IN IBADAN: SOCIO-SEXUAL CHARACTERISTICS, CLINICAL STAGE AT PRESENTATION, HISTOPATHOLOGY DISTRIBUTIONS AND HIV STATUS.

Background:Human Papillomavirus (HPV) infection persistence is the necessary but not sufficient cause of invasive cervical cancer (ICC). The effects of Human Immunodeficiency Virus (HIV) co-infection have been well documented. The purpose of this study was to describe our experience on the clinico-pathological characteristics of patients with cervical cancer and HIV status at a tertiary Hospital in Nigeria.Materials and Methods:This was a descriptive study among ICC patients presenting for clinical staging and biopsy for histological diagnosis at the Obstetrics and Gynaecology outpatient theatre of our hospital between January 2009 and February 2011.Results:Sixteen (6.8%) of the 248 patients with histologically confirmed ICC in this study were HIV positive. The mean age of all the participants was 55.4 (SD±10.2) years with the HIV positive patients’ younger than the HIV-negative and those that declined HIV testing. Coitarche was at lower age (18 [SD±4.4] vs 22[SD±3.4] years vs 24.5[SD±4.4], respectively). The modal lifetime sexual partners were four, one and two, respectively. Clinically, more HIV positive patients, presented at advanced stage of ≥ 2B. Also, the adenocarcinoma histological variant was slightly more among the HIV positive patients.Conclusion:HIV seemed relatively common among ICC patients and they presented at lower ages, at more advanced stages, earlier coitarche and more lifetime sexual partners. The proportion of adenocarcinoma histological types was slightly higher among the HIV positive patients compared with seronegative patients and those with unknown HIV status. Larger studies to substantiate these findings and ICC-HIV causal relationship are required.

Prevalence and distribution of human papillomavirus genotypes among women with high-grade squamous intraepithelial lesion and invasive cervical cancer in Ganzhou, China.

Human papillomavirus (HPV) infection can lead to the development of cervical cancer. This study assessed the genotype distribution of HPV of high-grade squamous intraepithelial lesion (HSIL) and invasive cervical cancer (ICC) in Ganzhou population. A total of 935 females who got HPV testing from January 2016 to July 2018 in the maternal and child health hospital of Ganzhou were enrolled in the study, including 806 HSIL and 129 ICC. HPV detection and genotyping were tested by HPV Geno-Array test kit. The overall HPV-positive rate was 74.0% in Ganzhou. Among the HSIL and ICC patients, the positive rates of HPV detection were 75.6% and 64.3%. Among the HSIL individuals, the most prevalent hr-HPV genotype was HPV 16. And the 4 common subtypes in decreasing order were HPV 52, 58, 33, and 18. Of the ICC patients, the most frequently hr-HPV subtype was HPV 16 followed by 18, 52, 58, and 59. Among the squamous cell carcinoma (SCC) patients, for hr-HPV genotypes, HPV 16, 18, 52, 58, and 59 were five most common subtypes. In patients with adenocarcinoma (ADC), the most common hr-HPV genotype was HPV 18, followed by HPV 16, 52, 56, 68, 73. And, we found U-shaped and S-shaped curves in the HPV distribution of different age groups. The prevalence and distribution of HPV genotypes in Ganzhou differed from other regions of China and Western countries. These results can serve as valuable reference for HPV vaccination programs for Ganzhou women.

Single type infection of human papillomavirus as a cause for high-grade cervical intraepithelial neoplasia and invasive cancer in Japan

To elucidate oncogenic human papilloma virus (HPV) types in Japan, HPV genotyping was performed in 1526 cervical intraepithelial neoplasia (CIN) and 371 invasive cervical cancer (ICC) patients with the novel Genosearch-31+5 HPV test. The HPV-positive rates were 89.3% and 90.8% in CIN and ICC. Regarding single-type infections, 13 internationally recognized high-risk (13HR) types excluding HPV 35, and probably HR HPV 53, 67, 69, and 70 were identified in ICC, suggesting that all these types may be oncogenic. HPV16 and 18 were identified in both SCC and adenocarcinoma (ADC). HPV HPV52, 31 and 58 (alpha-9) were predominantly detected in SCC, whereas HPV 18, 45, 39 and 59 (alpha-7) were in ADC. The prevalence of HPV 18 in SCC significantly decreased with increasing age of patients, whereas the opposite trend was observed in the other HR types. HPV18 is likely to induce SCC rapidly. All ICC cases aged 20–29 were positive for HPV 16 or 18, suggesting that present HPV 16, 18 vaccines may be quite effective to prevent ICC in young women.

Population-Based Assessment of HPV Genotype-Specific Cervical Cancer Survival: CDC Cancer Registry Sentinel Surveillance System.

BackgroundHuman papillomavirus (HPV) genotype influences the development of invasive cervical cancer (ICC); however, there is uncertainty regarding the association of HPV genotype with survival among ICC patients.MethodsFollow-up data were collected from 693 previously selected and HPV-typed ICC cases that were part of the Centers for Disease Control and Prevention Cancer Registry Surveillance System. Cases were diagnosed between 1994 and 2005. The Kaplan-Meier method was used to estimate five-year all-cause survival. A multivariable Cox proportional hazards model was used to estimate the effect of HPV genotype on survival after adjusting for demographic, tumor, and treatment characteristics.ResultsFive-year all-cause survival rates varied by HPV status (HPV 16: 66.9%, HPV 18: 65.7%, HPV 31/33/45/52/58: 70.8%, other oncogenic HPV genotypes: 79.0%, nononcogenic HPV: 69.3%, HPV-negative: 54.0%). Following multivariable adjustment, no statistically significant survival differences were found for ICC patients with HPV 16–positive tumors compared with women with tumors positive for HPV 18, other oncogenic HPV types, or HPV-negative tumors. Women with detectable HPV 31/33/33/45/52/58 had a statistically significant 40% reduced hazard of death at five years (95% confidence interval [CI] = 0.38 to 0.95), and women who tested positive for nononcogenic HPV genotypes had a statistically significant 57% reduced hazard of death at five years (95% CI = 0.19 to 0.96) compared with women with HPV 16 tumors. Few statistically significant differences in HPV positivity, tumor characteristics, treatment, or survival were found by race/ethnicity.ConclusionsHPV genotype statistically significantly influenced five-year survival rates among women with ICC; however, screening and HPV vaccination remain the most important factors to improve patient prognosis and prevent future cases.

Cervical cancer sociodemographic and diagnostic disparities in Florida: a population-based study (1981–2013) by stage at presentation

ABSTRACT Objective: Florida has one of the highest cervical cancer mortality rates and socioeconomically diverse populations in the United States. We used statewide population-based cancer registry data to assess disparities in cervical cancer stage at diagnosis. Design: Primary invasive adult female cervical cancer patients in the Florida Cancer Data Registry (1981–2013) were linked with 2000 United States Census data. Early (localized) and advanced (regional and distant) stage at diagnosis was assessed by age, race, ethnicity, neighborhood socioeconomic-, marital-, and smoking- status. Univariate and multivariable logistic regression models were fit to identify factors associated with the risk of advanced cervical cancer stage at diagnosis. Adjusted odds ratios (aOR) and corresponding 95% confidence intervals (95%CI) were calculated. Results: Of 18,279 women (meanage 51.3 years old), most were non-Hispanic (83.5%), white (79.1%), middle-low neighborhood socioeconomic status (NSES) (34.7%), married (46.0%), and never smoked (56.0%). Higher odds of advanced stage was observed for blacks (aOR: 1.42, 95%CI: 1.30–1.55, p < 0.001) compared to whites, Hispanics (1.15, 1.06–1.25, p = 0.001) compared to non-Hispanics, and middle-low (1.13, 1.02–1.25, p = 0.02) and low NSES (1.42, 1.28–1.57, p < 0.001) compared to high NSES. Previously (1.30, 1.21–1.39, p < 0.001) and never married (1.37, 1.27–1.48, p < 0.001) had higher odds of presenting with advanced stage versus married women. Never smokers had decreased odds of presenting with advanced stage compared to women with history of (1.41, 1.32–1.52, p < 0.001) or current (1.29, 1.18-1.42, p < 0.001)smoking status. Conclusions: There are cancer disparities in women of black race, Hispanic ethnicity and of middle-low and lowest NSES in Florida. Evidence-based interventions targeting these vulnerable groups are needed. Abbreviations: HPV: Human Papilloma Virus; CDC: Center for Disease Control and Prevention; SES: socioeconomic status; FCDS: Florida Cancer Data System; NSES: Neighborhood Socioeconomic Status; NPCR: National Program of Cancer Registries; IRB: Institutional Review Board; ACS: American Community Survey; SEER: Surveillance, Epidemiology and End Results; OR: Odds Ratio; CI: Confidence Interval

Chemoradiation therapy induces in vivo changes in gene promoter methylation & gene transcript expression in patients with invasive cervical cancer.

Background & objectives:Invasive cervical cancer patients are primarily treated with chemoradiation therapy. The overall and disease-free survival in these patients is variable and depends on the tumoral response apart from the tumour stage. This study was undertaken to assess whether in vivo changes in gene promoter methylation and transcript expression in invasive cervical cancer were induced by chemoradiation. Hence, paired pre- and post-treatment biopsy samples were evaluated for in vivo changes in promoter methylation and transcript expression of 10 genes (ESR1, BRCA1, RASSF1A, MYOD1, MLH1, hTERT, MGMT, DAPK1, BAX and BCL2L1) in response to chemoradiation therapy.Methods:In patients with locally advanced invasive cervical cancer, paired pre- and post-treatment biopsies after 10 Gy chemoradiation were obtained. DNA/RNA was extracted and gene promoter methylation status was evaluated by custom-synthesized methylation PCR arrays, and the corresponding gene transcript expression was determined by absolute quantification method using quantitative reverse transcription PCR.Results:Changes in the gene promoter methylation as well as gene expression following chemoradiation therapy were observed. BAX promoter methylation showed a significant increase (P< 0.01) following treatment. There was a significant increase in the gene transcript expression of BRCA1 (P< 0.01), DAPK1 and ESR1 (P< 0.05), whereas MYOD1 and MLH1 gene transcript expression was significantly decreased (P< 0.05) following treatment.Interpretation & conclusions:The findings of our study show that chemoradiation therapy can induce epigenetic alterations as well as affect gene expression in tissues of invasive cervical cancer which may have implications in determining radiation response.

Problem of Invasive Cervical Cancer’s Management in the Obstetric Gynecologic Department of the National Hospital Donka, Conakry

Introduction: The objectives of this study were to describe the diagnostic and therapeutic aspects, identify problems and evaluate the survival rate of invasive cervical cancer patients. Patients and method: It was a retrospective descriptive study of 7 years from 1 January 2006 to 31 December 2012. Records of invasive cervical cancer were histologically confirmed. The clinical and therapeutic data collected were transferred to Epi info 7 and SSPS version 18 software with a significance level p as used to provide information on the vital condition after confidential agreement. Kaplan Meier was used to assess the overall survival rate. Results: Invasive cancer of the cervix was frequent (58.79%) with an annual median rate of 16.7%, with extremes of 5.8% and 20.6%. 88.70% of the patients was referred from regions of the country (54.02%); the median age was 50 years with extremes of 16 and 84 years and a peak of 29.6% between 35 and 44 years; 76.20% were housewives; uneducated women were about 60.12%; Stage III was about 45.3%. Most of the patients were confirmed histologically after 30 days (68%). The means of treatment were surgery about 91 (29.26%), palliation 75 (24.12%), radiotherapy 59 (18.97%) and chemotherapy 41 (13.18%) with surgery (9, 65%) or radiotherapy (4.82%). The main complication was metrorrhagia, 164 cases (56.55%), with overall survival rate of 51.8% at 2 years and 5.1% at 5 years. Conclusion: Invasive cervical cancer in later stages is treated for low survival in the context of our work. Early detection and treatment of precancerous lesions would reduce the incidence and mortality of this cancer.