Changes in the incidence of cervical tumours by disease stage in a cytology-based screening programme

Objectives To report changes in incidence of cervical tumours by disease stage, following the introduction of an organized cytology-based screening programme. Methods An intention-to-screen study of a cytology-based screening programme targeting 1,219,000 women aged 25–64 in northern Italy was carried out. Based on the previously reported trend in total incidence of cervical cancer, the study period 1995–2014 was divided into 1995–1996 (pre-screening, or reference, years), 1997–1998 (screening implementation phase), 1999–2006 (transition phase, when incidence decreased), and 2007–2014 (steady-state phase, when incidence stabilized again). Tumour stage was categorized as preinvasive (cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ), early (pT1a), advanced (pT1b or greater, ypT), and unknown (pT1 not otherwise specified, pTx, missing information). Average annual incidence rates observed in each phase were compared with the expected (reference) rates, using the incidence rate ratio, calculated with a Poisson regression model. Results In the steady-state phase, incidence rate ratios were: CIN3, 1.55 (95% confidence interval, 1.41–1.70); early-stage squamous carcinoma, 0.49 (0.36–0.67); advanced-stage squamous carcinoma, 0.44 (0.33–0.57); unknown-stage squamous carcinoma, 0.69 (0.48–0.99); adenocarcinoma in situ, 1.44 (0.72–2.88); early-stage adenocarcinoma, 2.65 (0.82–8.53); advanced-stage adenocarcinoma, 1.03 (0.56–1.91); and unknown-stage adenocarcinoma, 0.46 (0.23–0.92). Conclusions After stabilization, changes in incidence by tumour stage included a 55% increase for CIN3 and a 50–55% decrease both for early- and advanced-stage squamous carcinoma, but no significant changes for glandular tumours. These data will serve to quantify the incremental impact of the implementation of human papillomavirus-based screening, introduced in 2015.

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Geolocation of uterine cervical neoplasms (UCN) in the context of a prevention program in Tucumán, Argentina.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13535 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13535-e13535

Author(s):

Silvia Victoria Holgado ◽

Ana Vinuales ◽

Daniel Gustavo Goroso ◽

William Tsutomu Watanabe ◽

Juan Jose Zarba ◽

...

Keyword(s):

Squamous Carcinoma ◽

Cross Sectional Study ◽

Adenocarcinoma In Situ ◽

Online Information ◽

Cervical Lesions ◽

Invasive Adenocarcinoma ◽

Cross Sectional ◽

Screening Population ◽

Short Time

e13535 Background: : UCN is one of the major public health problems in Tucumán, that must be related to the type of population to which it belongs (Rural or Urban). Geolocation allows the processing and analysis of geographic information whose results support decision-making in solving complex planning and management problems on the territory. The objective of this study is to carry out management quality controls of the PPCCUT (Programa de Prevención de Cáncer Cervical Uterino-Tucumán) to achieve adequate prevention and detection of uterine cervical lesions in the province. Methods: An observational cross-sectional study of 1343 women, (16-90 years), with a biopsy diagnosis UCN, under PPCCUT (years 2013-2020). Preanalytical work: allowed the review quality the registries and the diagnoses follow-up. Data recollection from SITAM (Online Information System for Screening), population registry database. Variables: Address: registered in SITAM, joined by information from the provincial female electoral roll 2019. Histological Diagnosis: High grade squamous intraepithelial lesion (HSIL), Invasive Squamous Carcinoma (ISC), Adenocarcinoma In situ (AIS), Invasive Adenocarcinoma (IDA). Analytical work: The conversion from address to latitude and longitude was performed by programming Google Sheet. This data was segmented by hospital center and opened in layers inside QGIS, as well as the map of Argentina. Results: Preanalytical. Register showed from 1343 patients received 1748 biopsies, were excluded 160 without address (incomplete data loading by the effectors). Lack of coordination in diagnosis area: 33 patients received first “in situ diagnosis” and in a short time later were consider “invasive lesions”. Some Patients had 2 bis 6 biopsies with same diagnosis. Analytical (geolocation): showed the influence of PPCCUT outside the province, including living abroad. It was found correlation between patients’ distribution with the population density. Conclusions: The importance of the work lays in the lack of antecedents in the application of the geolocation tool in programs of UCN in Tucumán and in other regions of Argentina. This allowed monitoring in different aspects of the programmatic management.

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Impact of concomitant immunosuppression on the presentation and prognosis of patients with melanoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9070 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 9070-9070

Author(s):

A. Frankenthaler ◽

M. Lee ◽

V. Seery ◽

S. Renzi ◽

M. Kinnaman ◽

...

Keyword(s):

Immune Suppression ◽

Early Stage ◽

Medical Center ◽

Primary Melanoma ◽

Tumor Location ◽

Disease Stage ◽

Disease Free Interval ◽

Melanoma Diagnosis ◽

Cutaneous Oncology

9070 Background: Melanoma has been reported to be susceptible to immune control. Therefore, we hypothesized that concomitant immune suppression might impact the course of the disease. Methods: We examined the Beth Israel Deaconess Medical Center Cutaneous Oncology Program database for pts with immune suppression at the time of melanoma diagnosis. The demographics and stage of these pts were compared to those in the database as a whole. In addition, 3 controls matched for age, gender, stage and tumor location were identified for each case and disease outcome was compared between cases and controls. Results: 19 pts were identified with melanoma and concomitant immune suppression in a database of 1820 melanoma pts. Other diagnoses included renal transplant (4) inflammatory arthritis (8), Multiple Sclerosis (2), and ulcerative colitis (3). Immunosuppressive meds included methotrexate, azothioprine, cyclosporine, prednisone, infliximab, and natalizumab. Melanoma stages at diagnosis were in situ 1, IB 7, IIA 1, IIB 1, IIIB 3, IIIC 5, and IV 1. Compared to the database as a whole, cases were more likely to be female (84% vs 45%) and have a higher disease stage (42% stage IIIB/C vs 26%). In addition, more cases appeared to have an amelanotic primary (21% vs. 5.4%) or an atypical mole syndrome (21% vs 10.2%). For pts who relapsed, the cases had a shorter disease free interval (DFI) (2.1 vs 9.7 yrs) than the controls. At a median f/up of 52 mos, 37% of the cases had relapsed and all of these pts had died. At a median f/up of 76 mos, 30% of the controls had relapsed yet only 47% of these pts had died. As a consequence, cases appeared more likely to have died of their disease than controls (42% vs 23%) (p=0.10). Conclusions: Compared to the general melanoma population, pts with concomitant immune suppression appear more likely to be female, have an amelanotic primary or atypical mole syndrome and more advanced disease at presentation. Although pts with concomitant immune suppression are equally likely to relapse compared to matched controls, those that relapse appear to have a shorter DFI and to be less likely to be salvaged, suggesting more aggressive tumor behavior in this setting. Thus, diagnosis and treatment of a primary melanoma at an early stage appears especially important in an immunosuppressed population. No significant financial relationships to disclose.

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Upregulation ofα3β1-Integrin in Podocytes in Early-Stage Diabetic Nephropathy

Journal of Diabetes Research ◽

10.1155/2016/9265074 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 12

Author(s):

Kaichiro Sawada ◽

Masao Toyoda ◽

Noriko Kaneyama ◽

Sawako Shiraiwa ◽

Hitomi Moriya ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Early Stage ◽

Integrin Expression ◽

Advanced Stage ◽

Podocyte Injury ◽

Expression Levels ◽

Podocyte Detachment ◽

Advanced Stages

Background. Podocyte injury plays an important role in the onset and progression of diabetic nephropathy (DN). Downregulation ofα3β1-integrin expression in podocytes is thought to be associated with podocyte detachment from the glomerular basement membrane, although the mechanisms remain obscure. To determine the mechanism of podocyte detachment, we analyzed the expression levels ofα3β1-integrin in podocytes in early and advanced stages of DN.Methods. Surgical specimens from DN patients were examined byin situhybridization, and the expression levels ofα3- andβ1-integrin subunits in glomeruli of early (n=6) and advanced (n=8) stages were compared with those of normal glomeruli (n=5). Heat-sensitive mouse podocytes (HSMP) were cultured with TGF-β1 to reproduce the microenvironment of glomeruli of DN, and the expression levels of integrin subunits and the properties of migration and attachment were examined.Results. Podocytes of early-stage DN showed upregulation ofα3- andβ1-integrin expression while those of advanced stage showed downregulation. Real-time PCR indicated a tendency for upregulation ofα3- andβ1-integrin in HSMP cultured with TGF-β1. TGF-β1-stimulated HSMP also showed enhancedin vitromigration and attachment on collagen substrate.Conclusions. The results suggested that podocyte detachment during early stage of DN is mediated through upregulation ofα3β1-integrin.

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Stage and histology influence the relationship between MDM2 promoter polymorphism and esophageal cancer and overall survival (OS)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21047 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21047-21047

Author(s):

H. J. Mackay ◽

P. Bradbury ◽

K. Asomaning ◽

W. Zhou ◽

M. Kulke ◽

...

Keyword(s):

Overall Survival ◽

Esophageal Cancer ◽

Early Stage ◽

Disease Stage ◽

Advanced Stage ◽

Mdm2 Snp309 ◽

Prognostic Role ◽

Histologic Subtype ◽

The Relationship

21047 Background: A single nucleotide polymorphism in the MDM2 promoter (SNP309) has been found to affect OS of advanced stage gastric adenocarcinoma (AD) and early stage squamous (SQ) cell carcinoma of the lung. The aim of this study was to evaluate the role of this polymorphism in the prognosis of esophageal cancer, another aerodigestive cancer. Methods: 150 early stage (E) and 118 locally advanced stage (LA) esophageal cancers were genotyped for MDM2 SNP309 using Taqman. The primary endpoint was overall survival (OS). Results: E disease: n=23 stage I; n=127 stage II. LA disease: n=93, Stage III; n=25, Stage IVA. AD comprised 215 (81%), while SQ comprised 45 (17%) of cases; 8 (3%) had poorly differentiated tumors. Median follow-up = 32 months. Median OS were 36 and 21 months for E and LA disease, respectively. Both histology and disease stage affected the relationship between SNP309 and esophageal cancer OS (see Table ). The wildtype T/T genotype conferred a worse OS in E patients (log-rank, p=0.03), especially those with AD (log-rank, p=0.003). In Cox proportional hazards interaction analyses, after adjusting for age, gender, stage and PS, there were statistically significant interactions between MDM2 SNP309 and disease stage (interaction p=0.004) and between MDM2 SNP309 and histologic subtype (AD vs. SQ)(interaction p=0.02). Thus, the direction of SNP309 association from our AD and E esophageal cancer patients are opposite to those of our SQ and LA esophageal cancer patients. However, our SQ and LA results are similar to the SQ lung cancer and advanced stage gastric cancers previously reported. This suggests that biologic mechanisms underpinning the prognostic role of SNP309 are dependent on extent of disease and histologic subtype. Conclusion: Histology and disease stage interact with the prognostic role of MDM2 SNP309 polymorphism in esophageal cancer OS. [Table: see text] No significant financial relationships to disclose.

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Causes of death in nodular lymphocyte predominant Hodgkin's lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e20016 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e20016-e20016

Author(s):

Anas M Saad ◽

Ahmed Afifi ◽

Mohamed Gad ◽

Muneer J. Al-Husseini ◽

Firas Baidoun ◽

...

Keyword(s):

Cardiovascular Disease ◽

Late Stage ◽

Hodgkin’S Lymphoma ◽

Causes Of Death ◽

Early Stage ◽

Hodgkin's Lymphoma ◽

Disease Stage ◽

Advanced Stage ◽

Stage Disease ◽

Late Stage Disease

e20016 Background: Nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL) accounts for 5% of all cases of HL. The outcomes of patients with NLPHL is generally regarded as better than those with classical HL. However, causes of death (COD) of patients with NLPHL have not been previously described. Methods: The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program was used to identify all patients with NLPHL diagnosed between 1990 and 2015. Patient characteristics and disease stage, using the Ann-Arbor system, was extracted and tabulated. COD were identified and proportions were calculated for deaths within 5 years and after 5 years of diagnosis for patients with early and late stage NLPHL. Results: We identified 1,937 cases of NLPHL. The majority were younger than 65 years (86%), white (70%), male (67%), and diagnosed between 2001-2015 (85%), when rituximab was introduced. Of all cases, 1336 (69%) were classified as early stage. At a median follow-up of 91 months (IQR 41, 152) for early stage disease, and 73 months (IQR 30-123) for late stage disease, the median cancer-specific or overall survival were not reached. The estimated 5-year survival was 92% and 81% for early stage and late stage disease, respectively. Of all patients with early stage NLPHL, 186 (14%) died by the end of 2015, and 87 (46%) deaths occurred within 5 years of diagnosis. During the first 5 years after diagnosis, COD was NLPHL in 30 (35%). Beyond 5 years from diagnosis, NLPHL was the COD in 27% followed by other cancers (23%), and cardiovascular disease (18%). Of all patients with late stage NLPHL, 107 (21%) died, and 75 (70%) of deaths occurred within 5 years of diagnosis. During the first 5 years after diagnosis, COD was NLPHL in 44 (59%). Beyond 5 years from diagnosis, cardiovascular disease was the COD in 25%, followed by NLPHL (22%). Conclusions: The prognosis of NLPHL is excellent. Of all patients with NLPHL, those with advanced stage disease are more likely to die of their disease within 5 years of diagnosis. Patients with early and advanced stage disease beyond 5 years of diagnosis are more likely to die of causes other than NLPHL.

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Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study

Blood ◽

10.1182/blood-2011-12-396556 ◽

2012 ◽

Vol 119 (25) ◽

pp. 6005-6015 ◽

Cited By ~ 61

Author(s):

Stephen J. Proctor ◽

Jennifer Wilkinson ◽

Gail Jones ◽

Gillian C. Watson ◽

Helen H. Lucraft ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Cox Regression ◽

Early Stage ◽

Univariate Analysis ◽

Central Element ◽

Disease Stage ◽

Advanced Stage ◽

Early Stage Disease ◽

Large Patient ◽

Stage Disease

Abstract The SHIELD program for Hodgkin lymphoma in patients 60 years of age or older, prospectively evaluated clinical features and outcome in a large patient cohort (n = 175). The central element was a phase 2 study of VEPEMB chemotherapy (n = 103, median age 73 years) incorporating comorbidity assessment. A total of 72 other patients were treated off-study but registered prospectively and treated concurrently with: ABVD (n = 35); CLVPP (n = 19), or other (n = 18). Of VEPEMB patients, 31 had early-stage disease (stage 1A/2A) and received VEPEMB 3 times plus radiotherapy. Median follow-up was 36 months. Complete remission (CR) rate (intention-to-treat) was 74% and 3-year overall survival (OS) and progression-free survival (PFS) were 81% and 74%, respectively. A total of 72 patients had advanced-stage disease (stage 1B/2B/3 or 4) and received VEPEMB 6 times. CR rate was 61% with 3-year OS and PFS of 66% and 58%, respectively. Of patients achieving CR, 13% with early-stage and 5% with advanced-stage disease progressed. Overall treatment-related mortality was 7%. In patients treated with curative intent with VEPEMB, ABVD, and CLVPP (n = 157), CR linked to several factors in univariate analysis. In a Cox regression model only, obtaining CR remained significant for OS and CR plus comorbidity and age for PFS. RS-EBV status had no significant effect on outcome.

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Differential Expression of Metastasis-Associated Genes in Papilla of Vater and Pancreatic Cancer Correlates With Disease Stage

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.9.2422 ◽

2001 ◽

Vol 19 (9) ◽

pp. 2422-2432 ◽

Cited By ~ 21

Author(s):

Helmut Friess ◽

Xiao-Zhong Guo ◽

Adrien A. Tempia-Caliera ◽

Akira Fukuda ◽

Marcus E. Martignoni ◽

...

Keyword(s):

Pancreatic Cancer ◽

In Situ Hybridization ◽

Early Stage ◽

Expression Patterns ◽

Tumor Biology ◽

Disease Stage ◽

Papilla Of Vater ◽

Advanced Tumor ◽

Tumor Stages

PURPOSE: Papilla of Vater cancer has a much better prognosis than pancreatic cancer. It is not known whether this is the result of differences in the tumor biology of the two malignancies. Because metastasis formation is a critical step in tumor progression and a negative prognostic factor, we compared the expression of nm23-H1 and KAI1, two metastasis-suppressing genes, in papilla of Vater cancer and pancreatic cancer. PATIENTS AND METHODS: Analysis was performed in nine normal human papilla of Vater samples, 27 papilla of Vater cancers, 16 normal pancreatic samples, and 29 pancreatic cancers. Expression of nm23-H1 and KAI1 was analyzed by Northern blot analysis and in situ hybridization. In addition, immunohistochemistry was performed to localize the respective proteins. RESULTS: There was no difference in nm23-H1 and KAI1 mRNA expression levels in normal versus cancerous papilla of Vater samples. In contrast, nm23-H1 and KAI1 RNA expression was upregulated in early tumor stages of pancreatic cancer and reduced in advanced tumor stages. When expression of nm23-H1 and KAI1 RNA was analyzed by use of in situ hybridization, normal epithelial cells of the papilla of Vater exhibited mRNA staining intensity similar to that of papilla of Vater cancer cells. Similar levels of nm23-H1 and KAI1 immunoreactivity also were observed in these samples. In contrast, early stage pancreatic cancer samples exhibited stronger nm23-H1 and KAI1 immunoreactivity than normal controls. Furthermore, early pancreatic cancer stages exhibited higher KAI1 and nm23-H1 immunostaining than advanced tumor stages. CONCLUSION: Differences in the expression patterns of the two tumor suppressor genes nm23-H1 and KAI1 may contribute to the different prognoses of papilla of Vater cancer and pancreatic cancer. Our findings support the hypothesis that biologic differences rather than earlier diagnosis influence the different outcomes of these two tumor entities.

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Stat3 Expression in Oral Squamous Cell Carcinoma: Association with Clinicopathological Parameters and Survival

The International Journal of Biological Markers ◽

10.1177/172460080602100307 ◽

2006 ◽

Vol 21 (3) ◽

pp. 175-183 ◽

Cited By ~ 19

Author(s):

N.G. Shah ◽

T.I. Trivedi ◽

R.A. Tankshali ◽

J.A. Goswami ◽

D.H. Jetly ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Early Stage ◽

Disease Stage ◽

Clinicopathological Parameters ◽

Early Event ◽

Advanced Stage ◽

Intense Staining

The present study sought to explore the occurrence of signal transducer and activator of transcription 3 (Stat3) in patients with oral squamous cell carcinoma (n=135) and its potential relationship with clinicopathological parameters and survival. Stat3 expression was studied by immunohistochemistry. Cytoplasmic or nuclear localization of Stat3 was observed in 62% of patients, whereas only nuclear Stat3 expression was found in 44%. Stat3 positivity in early-stage patients was 45% compared to 79% in advanced-stage patients. However, early-stage Stat3-positive patients showed a gradual increase in staining intensity, with intense staining seen in 52% of the tumors compared to 18% in Stat3-positive advanced-stage patients, where a gradual decrease in intensity expression was observed (p=0.001). Stat3 showed a significant positive correlation with disease stage (p=0.001), nodal status (p=0.033) and tumor size (p=0.001). Multivariate survival analysis using the Cox proportional hazard regression model showed that nuclear Stat3 was a significant independent prognosticator for both relapse-free survival (p=0.014) and overall survival (p=0.042) in early-stage patients. Our results indicated that Stat3 activation is an early event in oral squamous cell carcinoma and represents a potential risk factor for poor prognosis in early-stage patients.

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