Pancreatic adenosquamous carcinoma: A population level analysis of epidemiological trends and prognosis.

BACKGROUND: The incidence and mortality of pancreatic adenosquamous carcinoma (PASC) have received little attention. The goal of our study was to explore the overall epidemiological trend of PASC at the population level. METHODS: The Surveillance, Epidemiology, and End Results database was used to collect the incidence, incidence-based (IB) mortality, and patient details for PASC from 2000 to 2017. The Joinpoint regression tool was used to examine the trends in incidence and IB mortality. The Kaplan-Meier approach was used for survival analysis. Univariate and multivariate Cox regression analyses were used to determine the independent prognostic factors. RESULTS: We included 815 patients with PASC in the study. The incidence of PASC continuously increased from 2000 to 2017, with an annual percentage change (APC) of 3.9% (95% CI: 2.2%-5.7%, p < 0.05). IB mortality also increased continuously, with an APC of 5.0% (95% CI: 2.5%-7.6%, p < 0.05). Multivariate Cox regression analysis revealed that age, treatment, regional lymph node involvement, and tumor size were independent prognostic factors. Nomograms were created for PASC to predict 1- and 2-year survival probabilities, respectively. CONCLUSIONS: The incidence and IB mortality of PASC had a sustained and rapid increase, indicating that the preventive and treatment measures for PASC were not ideal. We must identify the significance of this condition as soon as possible, and commit greater attention and resources to PASC research.

Epidemiology and survival outcomes in adenosquamous carcinoma: a population-based study.

BACKGROUND: The relationship between the location of the primary tumor and survival of adenosquamous carcinoma (ASC) remains poorly understood. This study aimed to evaluate the impact of primary tumor location on the survival outcome of patients with ASC. METHODS: Patients with ASC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database with ≥ 150 cases per tumor location. The Kaplan-Meier method was used to generate survival curves and differences among them were compared using the log-rank test. On the other hand, Cox proportional hazards models were used to evaluate factors that had independent predictive effects on cancer-specific survival (CSS). RESULTS: A total of 14,829 eligible patients with ASC were included in this study. Lung and bronchus ASC accounted for 51.1%, followed by the cervix uteri (17.0%), corpus uteri (13.9%), pancreas (4.9%), esophagus (3.1%), gallbladder (2.5%), stomach (2.2%), colon and rectum (2.0%), head and neck (1.8%), and breast ASC (1.3%). The 5-year CSS of breast, cervix uteri, colon and rectum, corpus uteri, esophagus, gallbladder, head and neck, lung and bronchus, pancreas, and stomach ASC was 76.9%, 66.0%, 34.8%, 72.9%, 12.0%, 10.8%, 45.0%, 24.7%, 4.3%, and 17.3%, respectively. COX analysis demonstrated that the primary tumor location was an independent prognostic factor for CSS. Besides, the breast, uterine corpus, and cervix as well as head and neck ASC were significantly associated with better prognosis, while pancreas and gallbladder ASC were significantly associated with poor CSS; stomach and colorectal were roughly the same as ASC prognosis. CONCLUSION: Our study showed that the CSS of patients with ASC depends on the location of the primary tumor. Besides, tumor location is an important factor that should guide the use of chemotherapy and radiation.

Presentation, treatment, and prognosis of colorectal adenosquamous carcinoma: A contemporary analysis of the surveillance, epidemiology, and end results database.

INTRODUCTION: Colorectal adenosquamous carcinoma (ASC) represents <0.1% of colorectal cancers. Due to its rarity, there is paucity of data regarding its prognosis and treatment compared to other colorectal cancers. The aim of the study was to evaluate presentation, treatment and prognosis of colorectal ASC in comparison to adenocarcinoma (AC) and squamous cell carcinoma (SCC). METHODS: Adult patients diagnosed with colorectal AC, SCC, and ASC between 2000 and 2017 were identified using Surveillance, Epidemiology, and End Results database. RESULTS: Among the 446,132 patients diagnosed with colorectal cancer, 0.06% had ASC and were more likely to present with higher T stage and distant metastases compared to AC and SCC (p < 0.001). Major surgery was the primary treatment for colonic ASC, while for rectal ASC, chemotherapy and/or radiation were mainly utilized. Localized and distant colonic ASC had an unadjusted 5-year cause-specific survival that was worse than AC, while rectal ASC had the worst survival across all stages. CONCLUSION: Colorectal ASC usually present with advanced stage and have overall worse prognosis. Standardization of treatment strategies may improve survival in colorectal ASC.

Human papillomavirus-related head and neck adenosquamous carcinoma: A systematic review and individual patient data meta-analysis.

This work examined published papers of patients affected by human papillomavirus-related head and neck adenosquamous carcinoma. Demographic data, tumor site and sub-site, TNM stage, HPV status (positive VS negative) and the technique used for its identification, the treatments performed, follow-up time and patient's status at follow-up were assessed. Three papers including 26 patients resulted eligible for the study. The incidence of HPV-positive Adenosquamous Carcinomas located in the oropharynx was significantly higher than HPV-negative tumors (p = 0.01), especially if the origin of primary unknown tumors was considered within this anatomical site (p < 0.0001). HPV-positive Adenosquamous Carcinomas had a higher incidence of small primary tumor (Tx + T1) (p = 0.03) and bulky cervical lymph node metastasis (N2) at presentation (p = 0.02). HPV-positive and HPV-negative tumors had similar OS and DFS. Head & Neck HPV-positive Adenosquamous Carcinoma seems to act like HPV-positive conventional Squamous Cell Carcinoma, thus we suggest to determine the HPV status of Adenosquamous Carcinoma during the diagnostic phase.

Glassy cell carcinoma of the uterine cervix: 20-year experience from a comprehensive cancer center.

PURPOSE: Glassy cell carcinoma (GCC) of the uterine cervix is a rare entity. This study aims at describing the clinical characteristics and outcomes of cervical GCC patients treated in a comprehensive cancer center. MATERIAL AND METHODS: We retrospectively reported patients and tumors characteristics, therapeutic management, overall survival (OS), progression-free progression (PFS), relapse rates, and toxicities. RESULTS: Between 1994 and 2014, 55 patients were treated with curative intent. The median age at diagnosis was 41 years (range, 20-68). Among 22 patients with early stage tumors (IA2-IB1-IIA1), 17 had preoperative brachytherapy, followed by radical hysterectomy. Among 33 patients with locally advanced disease (≥IB2), 32 underwent chemoradiation±brachytherapy boost. After a median follow-up of 5.4 years (range, 0.15-21.7 years), 18/55 (33%) patients experienced tumor relapse. Local recurrence occurred in 2/22 (9%) patients with early disease (treated with upfront surgery) and in 3/32 (9%) patients with locally advanced disease. Most frequent relapses were distant, occurring in a total of 11/55 patients (20%). PFS rates at 5-year were 86.4% (95% CI: 63.4-95.4) for early stage versus 75.9% (95% CI: 55.2-89.2) for locally advanced stages, respectively (P=0.18). CONCLUSION: Large cohort data are warranted to guide the optimal management of GCC. From this retrospective analysis, a multimodal approach yielded to good disease control in early stages tumors. Given the high-risk of distant failure, consideration should be given to adjuvant chemotherapy in locally advanced disease.

Preoperative Conization and Risk of Recurrence in Patients Undergoing Laparoscopic Radical Hysterectomy for Early Stage Cervical Cancer: A Multicenter Study.

STUDY OBJECTIVE: To investigate the factors associated with poorer oncologic outcomes in patients undergoing laparoscopic radical hysterectomy (LRH) for early stage cervical cancer. DESIGN: Multicenter retrospective study. SETTING: Three gynecologic oncology referral centers. PATIENTS: Patients with International Federation of Gynecology and Obstetrics 2009 stage IA (positive lymphovascular space invasion)-IB1 cervical cancer between January 2006 and June 2018. INTERVENTIONS: LRH (Piver type II-III hysterectomies). Lymph-node dissection was accomplished according to the tumor characteristics. MEASUREMENTS AND MAIN RESULTS: Surgical and oncologic outcomes were analyzed. Overall, 186 patients met the inclusion criteria, 16 (8.6%) experienced a recurrence, and 9 (4.8%) died of the disease (median follow-up period 37.9 months). Surgery-related complications did not influence disease-free survival. All the recurrences (16/16; 100%) occurred in patients with stage IB1 disease (p = .02), and 15 (93.7%) in cases involving tumors ≥2 cm. No association between positive lymph node and recurrence was detected (p =.82). Patients who had a preoperative diagnosis through conization (93; 50%) had a significantly lower rate of recurrence than those who underwent cervical biopsy (93; 50%): 1/93 (1.1%) vs 15/93 (16.1%); p <.001). The subanalysis of patients with International Federation of Gynecology and Obstetrics stage IB1 cervical cancer showed that patients undergoing preoperative conization (vs cervical biopsy) were less likely to experience a recurrence (odds ratio 0.09; 95% confidence interval 0.01-0.55). CONCLUSION: We confirmed that LRH was associated with a recurrence rate similar to that reported in the Laparoscopic Approach to Cervical Cancer trial. Tumor size ≥2 cm represents the most important risk factor influencing disease-free survival. However, we found that preoperative conization plays a potentially protective role in patients with an IB1 tumor.

Clinicopathologic characteristics, survival, and treatments for gastric adenosquamous carcinoma: a population-based study.

Background: Gastric adenosquamous carcinoma (gasc) is a rare entity with distinctive characteristics that are not fully understood. In the present study, we evaluated the characteristics of this rare disease. Methods: The U.S. Surveillance, Epidemiology, and End Results program database was searched to determine the clinicopathologic features, prognostic factors, and treatments for 246 patients with gasc and 42,735 patients with gastric adenocarcinoma (gac). Results: Relative to gac, gasc is associated with higher proportions of cardia involvement, high-grade tumours, deep tumour invasion, metastatic lymph nodes, and chemotherapy treatment. In patients who underwent potentially curative surgery (pcs), gasc was associated with a higher proportion of radiotherapy use and poorer overall survival (p < 0.001), although no significant difference (p = 0.802) was observed after propensity score matching (psm). Multivariate analysis after psm revealed that the independent prognostic factors for gasc were TNM stage [hazard ratio (hr): 1.512; p = 0.021] and regional nodes examined (hr: 0.588; p = 0.02). In patients with advanced disease, no significant difference in survival between gasc and gac was observed (p = 0.212), although survival was significantly poorer for gasc after psm (p = 0.019). Multivariate analysis after psm revealed that the independent prognostic factors for gasc were invasion depth (hr: 1.303; p = 0.036) and chemotherapy (hr: 0.444; p < 0.001). Conclusions: Relative to gac, gasc was associated with more aggressive features, although survival outcomes were similar after pcs. Chemotherapy remains a mainstay of treatment for patients with advanced gasc, but its role remains unclear for patients who are undergoing pcs.

Adenosquamous carcinoma of the digestive system: a literature review.

Adenosquamous carcinoma (ASC), containing both adenocarcinoma and squamous cell carcinoma components, is rare in the digestive system. Limited data is available on ASC of the digestive system (AS-ASC), and the current evidence is available mainly in the form of case reports and case series. We performed a thorough search of the available literature and compiled a review on the epidemiology, histopathology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of AS-ASC. Non-specific clinical and imaging presentations and low diagnostic accuracy of biopsy lead to difficulties in preoperative diagnosis in a high proportion of patients and high malignancy. The pathogenesis remains obscure. Surgery remains the mainstay of treatment for AS-ASC. The role of chemoradiotherapy as an adjuvant treatment is still inconclusive. Key messages Metastatic linings and the lack of efficacious treatments lead to an unfavorable outcome in AS-ASC patients. Further research could help us understand the pathophysiology of AS-ASCand the unique needs of AS-ASC patients.

Lung Cancer in the Young.

INTRODUCTION: Median age at diagnosis of lung cancer is 70 years. Its presentation in patients 40 or younger is uncommon and it has been proposed that maybe it is a different disease due to its clinical characteristics and genetic makeup. There are a limited number of studies in this population and they report different clinic-pathological characteristics in comparison with older patients. METHODS: We described the incidence of lung cancer patients diagnosed at age 40 or younger at the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima-Peru; from 2009 to 2017 and evaluated the characteristic of NSCLC. Epidemiologic and clinic-pathological data was collected from clinical files. Analysis was carried out using SPSSvs19 software. RESULTS: We identified 3823 patients with lung cancer seen at INEN during the study period. Among these, 166 (4.3%) patients were 40 years or younger, and 137/166 (82.5%) were NSCLC. Median age at diagnosis was 36 years (range 14-40 years) and 59.1% of patients were female. A smoking history was present in 14.4% of patients. Frequent symptoms at diagnosis were cough (62.0%), chest pain (51.8%) and dyspnea (40.9%). Adenocarcinoma was the most common histological type (63.3%). Most patients had advanced disease at diagnosis (84.7%). The median overall survival was 8.2 months. CONCLUSIONS: The proportion of young patients with lung cancer in our population is higher than that reported in the most recent literature. Lung cancer in the young is mostly sporadic, more frequent in women, usually adenocarcinoma type and it presents with advanced disease, resulting in a very poor survival.

Cervical screening and risk of adenosquamous and rare histological types of invasive cervical carcinoma: population based nested case-control study.

OBJECTIVES: To examine the association of cervical cytology screening with the risk of adenosquamous cell carcinoma (ASC) and rare histological types of invasive cervical carcinoma (RICC), using comprehensive registry data, and to assess tumour human papillomavirus status of ASC and RICC. DESIGN: Nationwide, population based, nested case-control study. SETTING: Sweden. PARTICIPANTS: All cases of invasive cervical carcinoma in Sweden during 2002-11 (4254 confirmed cases after clinical and histopathological review). 338 cases were neither squamous cell carcinoma nor adenocarcinoma, including 164 cases of ASC and 174 cases of RICC (glassy cell carcinoma, clear cell carcinoma, small cell carcinoma, neuroendocrine cell carcinoma, large cell carcinoma, and undifferentiated carcinoma). 30 birth year matched controls from the general Swedish population were matched to each case by applying incidence density sampling. MAIN OUTCOME MEASURES: Conditional logistic regression was used to calculate odds ratios, interpreted as incidence rate ratios, for risk of ASC and RICC in relation to screening status and screening history, adjusted for education. Human papillomavirus distribution of ASC and RICC was based on available archival tumour tissues from most Swedish pathology biobanks. RESULTS: Women with two screening tests in the previous two recommended screening intervals had a lower risk of ASC (incidence rate ratio 0.22, 95% confidence interval 0.14 to 0.34) and RICC (0.34, 0.21 to 0.55), compared with women without any test. High risk human papillomavirus was detected in 148/211 (70%) cases with valid human papillomavirus results from tumour tissues. The risk reduction among women with tumours that were positive (incidence rate ratio 0.28, 0.18 to 0.46) and negative (0.27, 0.13 to 0.59) for high risk human papillomavirus was similar, compared with women who did not attend any test. CONCLUSIONS: Cervical screening is associated with reduced risk of ASC and RICC, and most ASC and RICC are positive for high risk human papillomavirus. This evidence provides a benchmark for evaluating future cervical screening strategies.

Isolated pulmonary metastases in patients with cervical cancer and the factors affecting survival after recurrence.

OBJECTIVES: The aim of this study was to assess the treatment options and survival of uterine cervical cancer (UCC) patients who develop isolated pulmonary metastases (IPM) and to establish risk factors for IPM. MATERIAL AND METHODS: Data from patients diagnosed with UCC between June 1991 and January 2017 at the Gynecological Oncology Department, Tepecik Training and Research Hospital, were investigated. In total, 43 cases with IPM were evaluated retrospectively. Additionally, 172 control patients diagnosed with UCC without recurrence were matched according to the International Federation of Gynecology and Obstetrics (FIGO) 2009 stage when the tumor was diagnosed. They wereselected using a dependent random sampling method. RESULTS: Of the 890 patients with UCC, 43 (4.8%) had IPM. The presence of lymphovascular space invasion (LVSI) and a mid-corpuscular volume (MCV) < 80 fL were statistically significant prognostic factors for IPM development in UCC patientsaccording to univariate regression analyses, and the presence of LVSI, a hemoglobin level < 12 g/dL, and an MCV < 80 fLwere statistically significant according to the multivariate regression analyses. We were unable to assess the role of lymph node status (involvement or reactive) as a prognostic factor in the development of IPM, because only seven patients (16.2%) in the case group underwent lymph node dissection. CONCLUSIONS: IPM typically develops within the first 3 years after the diagnosis of UCC, and survival is generally poor. An MCV < 80 fL and the presence of LVSI are significant risk factors for IPM development.

[Clinical Characteristics and Prognostic Factors of Lung Adenosquamous Carcinoma 
in SEER Database between 2010 and 2015].

BACKGROUND: The incidence and the mortality of lung cancer rank first among all malignant tumors and it seriously affects human health. The common types of non-small cell lung cancer (NSCLC) are adenocarcinoma and squamous carcinoma with clinical research and more attention, while adenosquamous carcinoma is a rare pathological subtype of lung cancer, which clinical features and prognostic factors are not yet fully understood. The purpose of this study is to analyze the clinical features and prognosis of lung adenosquamous carcinoma, and construct a nomogram to predict the patients' prognosis. METHODS: We obtained the data of adenosquamous carcinoma patients diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database of the United States, and compared their clinical features and prognosis with those of lung adenocarcinoma and lung squamous cell carcinoma patients in the same period. Then we used univariate and multivariate analyses to explore the independent prognostic factors of adenosquamous carcinoma. Finally, we constructed and validated a nomogram to visually predict the outcomes of lung adenosquamous carcinoma. RESULTS: 1,453 patients with lung adenosquamous carcinoma were finally included. Compared with patients with lung adenocarcinoma and lung squamous cell carcinoma, the distributions of lung adenocarcinoma patients in most of the variables were medium between lung adenocarcinoma and squamous cell carcinoma. The prognosis of adenosquamous carcinoma was better than that of lung squamous cell carcinoma, but worse than that of lung adenocarcinoma. Multivariate analysis showed that age, differentiation, tumor-node-metastasis (TNM), surgery, and chemotherapy were independent prognostic factors (all P were less than 0.001). We constructed a nomogram with a C-index of 0.783 (0.767-0.799). The distinction test and consistency test showed that the nomogram could predict the patient's prognosis effectively. CONCLUSIONS: Lung adenosquamous carcinoma has unique clinical, pathological, and prognostic characteristics. Age, differentiation, T, N, M, surgery, and chemotherapy status are independent predictors of prognosis in patients with adenosquamous carcinoma. Our nomogram can efficiently predict the prognosis of patients.

Progress in the Treatment and Outcomes for Early-Stage Non-Small Cell Lung Cancer.

PURPOSE: The purpose of this study is to assess temporal trends in population-based treatment and survival rates in patients with early-stage non-small cell lung cancer (NSCLC). METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Chi-square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 23.0. RESULTS: Fifty-seven thousand and eighty-eight NSCLC patients with early-stage disease from 1988 to 2014 were identified. 6409 (11.2%) were diagnosed in 1988-1994, 5800 (10.2%) 1995-1999, 13,031 (22.8%) 2000-2004, 15,786 (27.7%) 2005-2009, and 16,062 (28.1%) 2010-2014. We observed a significant increase in the proportion of older patients, adenocarcinoma histology, and rate of wedge resection over the study period. The five-year overall survival (OS) for the entire cohort was 63.3%. Those undergoing resection without adjuvant therapy had the highest outcomes. Lobectomy was associated with better outcomes compared to wedge resection or pneumonectomy. A significant difference in five-year OS by year of diagnosis (1988-1994: 58.8% vs. 1995-1999: 60.6% vs. 2000-2004: 63.2% vs. 2005-2009: 66.1%; p < 0.001) was observed. This significant OS difference was also observed regardless of age, surgery type, and T stage, but also only in those with adenocarcinoma. On multivariable analysis, year of diagnosis, age, gender, race, treatment and surgery type, histology, T stage, and tumor grade remained independent prognostic factors for OS. CONCLUSIONS: Overall survival for early-stage NSCLC has significantly improved over the recent decades despite an increasing proportion of older patients and those undergoing sublobar resection or SBRT. This finding may be limited to those with adenocarcinoma.

Histology as Prognostic Factor in Early-Stage Cervical Carcinoma. Experience in a Third-Level Institution.

BACKGROUND: Cervical carcinoma (CC) is one of the most frequent neoplasms, especially in developing countries. The most common histopathological type is squamous cell carcinoma (SCC), followed by adenocarcinoma (AC) and adenosquamous carcinoma (ASC). Prognosis according to histological type is controversial. OBJECTIVE: The objective of this study is to describe and compare the prognoses of the most common histologies of CC in the early stages. MATERIALS AND METHODS: We reviewed records of patients attended at the Instituto Nacional de Cancerología of Mexico with CC surgically treated Stages IA2-IB1 and IIA1, including the histological types SCC, AC, and ASC. Patients who had another malignant neoplasm, cervical cancer in situ, locally advanced neoplasm, and metastatic neoplasm were excluded from the study. A descriptive and comparative analysis was conducted. Overall survival (OS) and disease-free period were calculated for each histological type with the Kaplan-Meier method and were compared with the log-rank test. RESULTS: A total of 202 records were obtained, of which 131 (64.9%) had SCC, 57 (28.2%) AC, and 14 (6.9%) ASC. The 5-year DFS was 94.4% for SCC, 98.1% for AC, and 92.3% for ASC, without a statistically significant difference (p = 0.55). The 5-year OS for SCC was 97.9%, for AC was 97.8%, and for ASC was 100%, without a statistically significant difference (p = 0.702). CONCLUSIONS: DFS and OS did not differ between the most common histological types of CC at the early stages.

Human papillomavirus prevalence in lung carcinomas in Bulgaria.

A possible association between high-risk human papillomaviruses (HPV) and lung cancer has been investigated for decades with discrepant results. The aim of this study was to determine the prevalence of HPV16 and 18 in Bulgarian patients with lung cancer. Two hundred and nine biopsy specimens from patients with histologically proven lung cancer and without cancer were analyzed. Each sample was subjected to three parallel PCRs using broad spectrum GP5+/6+ primers and type-specific (TS) primers for HPV types 16 and 18. Of the 132 lung carcinoma samples, 33 (25%) were positive for HPV16 and/or HPV18 by TS PCR whereas only five (3.8%) samples were HPV positive by consensus PCR. All non-malignant controls were HPV negative. HPV18 was the more prevalent, being found in 11.4% of samples, followed by HPV16 in 9.1% samples; 4.5% of lesions were positive for both HPV16 and HPV18. HPV16/18 were most prevalent in small cell carcinoma (29.2%) and least prevalent in squamous cell carcinoma (23.3%). HPV was only detected in squamous cell carcinoma and adenosquamous carcinoma by consensus PCR. This study revealed a high HPV16/18 prevalence in lung carcinoma samples from Bulgarian patients when TS PCR was used to detect them. The difference between HPV positivity as detected by consensus and by TS PCR was significant, indicating the importance of methodological issues in explaining the discrepancies between previous studies. HPV18 was more common than HPV16. No association between HPV16/18 status and histopathological diagnosis was identified.

Differential HPV16 variant distribution in squamous cell carcinoma, adenocarcinoma and adenosquamous cell carcinoma.

Human Papillomavirus 16 (HPV16) causes 70% of invasive cervical cancers (ICC) worldwide. Interaction between HPV16 genetic diversity, host genetics and target tissue largely determine the chances to trigger carcinogenesis. We have analyzed the differential prevalence of viral variants in 233 HPV16-monoinfected squamous (SCC), glandular (ADC) and mixed (ADSC) ICCs from four continents, assessing the contribution of geographical origin and cancer histology. We have further quantified the contribution of viral variants and cancer histology to differences in age at tumor diagnosis. The model fitted to the data explained 97% of the total variance: the largest explanatory factors were differential abundance among HPV16 variants (78%) and their interaction with cancer histology (9.2%) and geography (10.1%). HPV16_A1-3 variants were more prevalent in SCC while HPV16_D variants were increased in glandular ICCs. We confirm further a non-random geographical structure of the viral variants distribution. ADCs were diagnosed at younger ages than SCCs, independently of the viral variant triggering carcinogenesis. HPV16 variants are differentially associated with histological ICCs types, and ADCs are systematically diagnosed in younger women. Our results have implications for the implementation of cervical cancer screening algorithms, to ensure proper early detection of elusive ADCs.

Follow-up of women with cervical cytological abnormalities showing atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion: a nationwide cohort study.

BACKGROUND: Atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion in abnormal cervical cytology among young women in cervical cancer screening is an increasing health burden, and comparative effectiveness studies of different management options for such diagnoses are needed. OBJECTIVE: The objective of the study was to compare the incidence of invasive cervical cancer, following different management options pursued after an atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion index smear. STUDY DESIGN: In this nationwide cohort study, we included all women aged 22-50 years and resident in Sweden 1989-2011 and with at least 1 cervical smear registered during the study period (n = 2,466,671). Follow-up of a first atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion cytological diagnosis within 25 months was classified as repeat cytology, colposcopy/biopsy, or without further assessment. Incidence rate ratios and 95% confidence intervals of subsequent cervical cancer within 6.5 years following atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion were estimated using Poisson regression by age group and management strategy. RESULTS: Women managed with repeat cytology within 6 months after atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology had a similar risk of cervical cancer compared with colposcopy/biopsy (incidence rate ratio, 1.1, 95% confidence interval, 0.5-2.5, and incidence rate ratio, 2.0, 95% confidence interval, 0.6-6.5, respectively) among women aged 22-27 years. For women aged 28 years and older, women managed with repeat cytology had a higher risk for cervical cancer than women managed with colposcopy/biopsy. CONCLUSION: Our findings suggest that women with a first cytological diagnosis of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion up to age 27 years may indeed be safely followed up with repeat cytology within 6 months. A large amount of colposcopies that are currently performed in this group, therefore, could safely be discontinued.

The nature of early-stage endometrial cancer recurrence-A national cohort study.

BACKGROUND AND AIMS: The aim of the study was to present a comprehensive analysis of disease recurrence in a large Danish cohort of women with early-stage endometrial cancer treated according to national guidelines. METHODS: All women diagnosed with stage I or II endometrial cancer in 2005-2009 were included in a population-based historical cohort derived from the Danish Gynaecological Cancer Database. Disease recurrence up to 3 years after the primary diagnosis was identified using national registers and hospital charts. Follow-up on survival ended on 31st December 2014. We evaluated the predictive value of clinico-pathological and sociodemographic variables using multivariate logistic regression. RESULTS: Recurrence within 3 years of the primary treatment was diagnosed in 183 (7%) of the included 2612 women. Site of recurrence significantly impacted on overall survival as the 5-year survival rate was 64.8% for women with vaginal recurrence and 17.5% in women with distant recurrence. Factors predictive of recurrence included the International Federation of Gynaecology and Obstetrics (FIGO) stage (OR: IB = 1.91, stage II = 3.91), Charlson comorbidity index of 3 (OR 1.86), non-endometrioid histology (OR 1.81) and being outside of the workforce (OR 1.81). Vaginal recurrence was predicted by FIGO stage only (OR: IB = 1.88, II = 2.79), while extra-vaginal recurrence was predicted by FIGO stage (OR: IB = 2.12, II = 3.31), Charlson comorbidity index of 3 (OR 1.88) and non-endometrioid histology (OR 2.51). CONCLUSIONS: Future research should seek to understand the underlying mechanisms of the identified predictive factors to improve recurrence prediction and to reduce morbidity and mortality.

Is cervical screening preventing adenocarcinoma and adenosquamous carcinoma of the cervix?

While the incidence of squamous carcinoma of the cervix has declined in countries with organised screening, adenocarcinoma has become more common. Cervical screening by cytology often fails to prevent adenocarcinoma. Using prospectively recorded cervical screening data in England and Wales, we conducted a population-based case-control study to examine whether cervical screening leads to early diagnosis and down-staging of adenocarcinoma. Conditional logistic regression modelling was carried out to provide odds ratios (ORs) and 95% confidence intervals (CIs) on 12,418 women with cervical cancer diagnosed between ages 30 and 69 and 24,453 age-matched controls. Of women with adenocarcinoma of the cervix, 44.3% were up to date with screening and 14.6% were non-attenders. The overall OR comparing women up to date with screening with non-attenders was 0.46 (95% CI: 0.39-0.55) for adenocarcinoma. The odds were significantly decreased (OR: 0.22, 95% CI: 0.15-0.33) in up to date women with Stage 2 or worse adenocarcinoma, but not for women with Stage1A adenocarcinoma 0.71 (95% CI: 0.46-1.09). The odds of Stage 1A adenocarcinoma was double among lapsed attenders (OR: 2.35, 95% CI: 1.52-3.62) compared to non-attenders. Relative to women with no negative cytology within 7 years of diagnosis, women with Stage1A adenocarcinoma were very unlikely to be detected within 3 years of a negative cytology test (OR: 0.08, 95% CI: 0.05-0.13); however, the odds doubled 3-5 years after a negative test (OR: 2.30, 95% CI: 1.67-3.18). ORs associated with up to date screening were smaller for squamous and adenosquamous cervical carcinoma. Although cytology screening is inefficient at preventing adenocarcinomas, invasive adenocarcinomas are detected earlier than they would be in the absence of screening, substantially preventing Stage 2 and worse adenocarcinomas.

Analysis of SEER Adenosquamous Carcinoma Data to Identify Cause Specific Survival Predictors and Socioeconomic Disparities.

BACKGROUND: This study used receiver operating characteristic curve to analyze Surveillance, Epidemiology and End Results (SEER) adenosquamous carcinoma data to identify predictive models and potential disparities in outcome. MATERIALS AND METHODS: This study analyzed socio-economic, staging and treatment factors available in the SEER database for adenosquamous carcinoma. For the risk modeling, each factor was fitted by a generalized linear model to predict the cause specific survival. An area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. RESULTS: A total of 20,712 patients diagnosed from 1973 to 2009 were included in this study. The mean follow up time (S.D.) was 54.2 (78.4) months. Some 2/3 of the patients were female. The mean (S.D.) age was 63 (13.8) years. SEER stage was the most predictive factor of outcome (ROC area of 0.71). 13.9% of the patients were un-staged and had risk of cause specific death of 61.3% that was higher than the 45.3% risk for the regional disease and lower than the 70.3% for metastatic disease. Sex, site, radiotherapy, and surgery had ROC areas of about 0.55-0.65. Rural residence and race contributed to socioeconomic disparity for treatment outcome. Radiotherapy was underused even with localized and regional stages when the intent was curative. This under use was most pronounced in older patients. CONCLUSIONS: Anatomic stage was predictive and useful in treatment selection. Under-staging may have contributed to poor outcome.