International Journal of Cancer最新文献

Women 30-59 years were allocated to either HPV-based screening or cytology-based screening in this Danish health care policy trial. The optimal triage of HPV-positive women could be a combination of cytology triage with HPV genotyping or p16/Ki67 staining. We report number of screen positives, colposcopies, and cervical lesions of three different triage algorithms (p16/Ki67, HPV16/18, or HPV16/18/31/33/52) in HPV-positive women with low-grade cytological abnormalities. We included 178,317 women with a sample in 2021 of which 91,517 were screened with HPV and 86,800 with cytology. All women were followed for 18 months. Almost three times as many women screened positive with HPV-based screening compared to cytology-based screening (RR 2.99, 95% 2.93-3.05) and colposcopies derived from the screening program were also more common (RR 1.68, 95% 1.63-1.73). p16/Ki67 triage resulted in more colposcopies (RR 1.86, 95% 1.76-1.95) than HPV16/18 (RR 1.54, 95% 1.44-1.65) and HPV16/18/31/33/52 (RR 1.63, 95% 1.55-1.71). The excess in colposcopy referrals was reduced when non-screening-derived colposcopies were included (intention-to-treat). Nevertheless, more women with CIN2 or worse were detected in the HPV group than in the cytology group per screened woman; in the p16/Ki67 triage group (RR 1.65, 95% 1.54-1.77), in the HPV16/18 group (RR 1.36, 95% 1.23-1.50), and in the HPV16/18/31/33/52 group (RR 1.48, 95% 1.37-1.59). HPV-based screening, as compared with cytology screening, resulted in more screen positives, but all three triage algorithms substantially reduced the excess number of referrals to colposcopy. p16/Ki67 compared to triage with HPV16/18 may detect more cervical lesions.

Cervical cancer incidence has increased in several high-income countries over the last decades. During the same period, many screening programs have shifted their primary method from cytology to the more sensitive HPV test. To better understand the increasing incidence, we visualized the incidence trends by mode of detection (screen-detected, interval cancers, cancers in non-participants, or cancers in those outside screening target ages) and by cancer morphology type using segmented regression. We also assessed the effects of the primary test method on the risk of screen-detected and interval cancers using Poisson regression. The study population consisted of all individuals diagnosed with cervical cancer (n = 4472) during 1996-2022 in Finland. An increase in cervical cancer incidence was observed during the 2010s, predominantly among individuals within the screening age. A clear upward trend was evident among both screening participants and non-participants. Notably, the incidence of screen-detected cervical cancer rose sharply after approximately 2013. The introduction of HPV-based screening was associated with an increased detection rate of screen-detected cancers (RR = 1.4, 95% CI = 1.1-1.7) compared to cytology testing. Conversely, the risk of interval cervical cancer was reduced when the preceding screening method was an HPV test (RR = 0.29, 95% CI = 0.21-0.38) compared to cytology. Our results imply that the initiation of HPV testing has improved the detection of prevalent cancers, but changes in risk factors also contribute to the rising incidence of cervical cancer.

DNA methylation analysis of self-collected samples has shown potential for primary endometrial cancer detection. Here, we aimed to explore DNA methylation testing as a non-invasive alternative for post-treatment surveillance. Endometrial cancer patients (n = 43) without recurrence collected pre- and post-treatment cervicovaginal self-samples and urine at home. Additionally, 17 patients with recurrence provided these samples at the time of recurrence. Healthy controls were used as reference. In total, 207 cervicovaginal self-samples and 203 urine samples were tested for nine markers (ADCYAP1, BHLHE22, CDH13, CDO1, GALR1, GHSR, HAND2, SST and ZIC1) using quantitative methylation-specific PCR. Diagnostic performance was assessed using previously established logistic regression models. In patients without recurrence, most marker levels decreased post-treatment compared to pre-treatment, in both sample types. DNA methylation positivity in cervicovaginal self-samples reduced from 90.7% pre-treatment to 19.5% post-treatment (p < .0001). In urine, a decrease from 80.5% to 20.9% was observed (p < .0001). In patients with recurrence, DNA methylation levels of CDH13, CDO1, GALR1, GHSR and HAND2 in cervicovaginal self-samples, and CDO1, GHSR and HAND2 in urine, were higher than in patients without recurrence. DNA methylation positivity was 62.5% in cervicovaginal self-samples and 58.8% in urine among patients with any recurrence, and 100% in cervicovaginal self-samples and 90.0% in urine of patients with a local recurrence specifically. These findings support methylation-based testing as a promising post-treatment surveillance method for endometrial cancer patients. This non-invasive approach could reduce the follow-up burden on patients and healthcare, alleviating challenges related to resource constraints while improving patient comfort.

Human papillomavirus (HPV) vaccination, implemented in multi-cohort vaccination programs in Denmark since 2008, has led to a decrease in the incidence of cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3). However, it remains unclear if the beneficial impact of this vaccination approach applies to all educational levels. In the present study, we estimated the incidence of cervical cancer and CIN3 during 2006-2023, overall and stratified by education. Information on all cases of cervical cancer and CIN3 and on education was obtained from high-quality, nationwide registries. We calculated age-standardized and age-specific incidence rates and calculated estimated annual percentage change (EAPC) with corresponding 95% confidence intervals (CI) for the early HPV vaccination period (2006-2012) and the late HPV vaccination period (2013-2023). We observed a decrease in age-standardized incidence of cervical cancer in the late vaccination period only among women with medium or long education. Impact was particularly found among women aged 20-29 years with medium (EAPC_{2013-2023[medium]} = -14.2, 95% CI: -15.9; -12.5) or long (EAPC_{2013-2023[long]} = -13.9, 95% CI: -15.1; -12.7) education. For CIN3, an increase in incidence was seen in the early vaccination period followed by a significant decrease in the late vaccination period, overall and stratified by education. However, in age-specific analyses, the decrease was only seen for the youngest women. Even in a country with free-of-charge multicohort HPV vaccination programs, the beneficial impact was most apparent among women with medium or long education, suggesting that educational inequalities still exist.

There is limited data regarding the rare and aggressive colorectal neuroendocrine carcinoma (CR-NEC). In this large prospective study, molecular-clinical characteristics and treatment outcomes following palliative chemotherapy are reported for 163 metastatic CR-NEC patients, with a comparison to a population-based prospective cohort of 263 metastatic colorectal adenocarcinoma (CR-AC) patients. Eighty-three percent of CR-NEC received first-line platinum-etoposide, while 98% of CR-AC patients received first-line fluorouracil-based chemotherapy. Disease control rate across all first-line regimens in CR-NEC and CR-AC was 43% vs. 74%, immediate progressive disease 46% vs. 15%, progression-free survival 2.4 months (m) (95% CI 2.1-3.3) vs. 7.7 m (95% CI 6.9-8.5), and overall survival 6.7 m (95% CI 5.6-8.8) vs. 16.8 m (95% CI 13.7-20.3), all, p < .001. CR-NEC more often had synchronous metastases, worse performance status, and symptom burden at treatment initiation than CR-AC (all, p < .001). Two-year survival was 9% vs. 37% in CR-NEC and CR-AC (p < .001). BRAF mutations were frequent in CR-NEC and CR-AC (26% vs. 20%, p = .153) and associated with shorter OS in CR-NEC and CR-AC (p = .025 and p = .003). KRAS mutations were less frequent in CR-NEC than CR-AC (34% vs. 45%, p = .041), but only associated with shorter OS in rectal NEC (p = .04). The frequencies of APC and TP53 mutations were similar between the cohorts and did not impact survival. Metastatic CR-NEC and CR-AC are clinically distinct, with NEC demonstrating more aggressive features, limited treatment effect, and worse prognosis. Although they share important driver mutations, the underlying reason for their marked clinical differences remains unclear.

Distinct recurrence patterns of gastric cancer (GC) and Siewert II/III gastroesophageal junction cancer (GEJC) following curative resection and adjuvant chemotherapy remain unclear. We aimed to investigate the initial recurrence patterns of GC/GEJC following curative resection and adjuvant chemotherapy. We retrospectively analyzed recurrence sites and timing in 1255 patients with GC/GEJC (338 with GEJC; 917 with GC) treated with curative resection and adjuvant chemotherapy (2011-2018). Univariate and multivariate analyses were used to identify predictors of recurrence patterns. Of the 430 patients who experienced recurrence, complete data were available for 352 (124 with GEJC; 228 with GC). In GEJC, distant recurrence was predominant (47.6%), followed by multifocal (22.6%), peritoneal (15.3%), and locoregional (14.5%) recurrence. Peritoneal metastases occurred primarily within four postoperative years, with two late exceptions. In GC, multifocal recurrence was the most frequent (36.8%), followed by distant (29.8%), peritoneal (26.8%), and locoregional (6.6%) recurrence. A notable proportion of patients with GC developed peritoneal and distant metastases annually after surgery, even beyond 5 years postoperatively. Most recurrences occurred within 3 years (81.5% GEJC; 77.2% GC). Multivariate analysis identified GEJC as an independent risk factor for locoregional (hazard ratio [HR], 1.953; p = .008) and distant recurrences (HR, 1.618; p = .004). Recurrence patterns after curative resection and adjuvant chemotherapy vary significantly between patients with GEJC and those with GC, and surveillance strategies should be tailored according to their respective characteristics. Intensive follow-up within the first 3 years is recommended for patients with GC/GEJC.

Of all world regions, countries in the Eastern Mediterranean region report the highest breast cancer mortality rates. In Libya, 65.5% of patients are diagnosed at advanced stages (III-IV). To address this, in 2023 we trained 46 female healthcare providers from four centers (three polyclinics and one hospital) in Misrata on breast cancer early detection. These healthcare providers were trained as master trainers. They first received theoretical training on breast cancer risk factors, early detection, and clinical breast examination (CBE). They then received practical training with silicone breast models and were trained to perform clinical examinations on female volunteers while under supervision. We assessed Knowledge, Attitude, and Practices using pre- and post-study questionnaires. Clinical skills were evaluated during examinations using a standardized CBE skills checklist. We saw significant improvements in knowledge scores following training (73.3%-84.3%, p-value <.001). Understanding of risk factors increased substantially, including early menarche (34.1%-86.4%, p < .001); late menopause (27.3%-77.3%, p < .001); and obesity (50%-86.4%, p = .002). "CBE master trainer" status was achieved by 85% (n = 39) on their first assessment, with the remaining 15% (n = 7) succeeding after completing additional training. This study is the first on breast cancer early detection through primary health care services in Libya. We show that structured training significantly improves knowledge of risk factors and CBE skills. This training provides a foundation on which Libya can implement a sustainable breast cancer early detection strategy to reduce the burden of this disease.

Nasopharyngeal carcinoma (NPC) remains a major challenge due to the high incidence of recurrence, often leading to therapeutic failure. Early detection of recurrence is critical, yet effective surveillance methods are limited. This study aims to evaluate the utility of Epstein-Barr virus (EBV) DNA detection in nasopharyngeal brush samples for identifying recurrent NPC. A total of 187 NPC patients who had undergone radical radiotherapy with or without chemotherapy were included. EBV DNA levels in both nasopharyngeal brush and plasma samples were analyzed using real-time quantitative PCR. Head and neck MRI, sinus endoscopy examination, and biopsy of suspicious lesions were used as the gold standard to confirm recurrence. Patients without recurrence after more than 1 year of follow-up served as controls. Nasopharyngeal brush EBV DNA detection demonstrated significantly higher sensitivity (95.7%) for detecting recurrence compared to plasma EBV DNA testing (61.4%), with comparable specificity (94.0% vs. 96.6%). The positive predictive value was similar between methods, whereas the negative predictive value was markedly higher for the nasopharyngeal brush group (97.3% vs. 80.7%). These findings suggest that EBV DNA detection in nasopharyngeal brush samples is a highly sensitive and minimally invasive supplementary tool for monitoring NPC recurrence. This approach offers superior sensitivity and an improved negative predictive value compared to plasma EBV DNA testing, and may enhance early surveillance and clinical management of NPC recurrence.