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Background Female-specific cancers, particularly breast, cervical, ovarian, and uterine cancers, account for nearly 40% of all cancers in women. This study aimed to analyze the global epidemiological trends of these cancers from 1990 to 2021, offering insights into their evolving patterns and providing valuable information for health policymakers to allocate healthcare resources more effectively. Methods Data from the Global Burden of Disease Study 2021 (GBD 2021) were used to comprehensively assess the global incidence, mortality, and disability-adjusted life years (DALYs) of female-specific cancers. Age-standardized rates facilitated cross-regional comparisons, accounting for differences in population size and demographics. The socio-demographic index (SDI) was employed to categorize regions and evaluate correlations between cancer burden and economic level. In addition, risk factors attributable to female-specific cancer deaths and DALYs were assessed based on the comparative risk assessment model of the GBD project. Results From 1990 to 2021, the global burden of female-specific cancers increased at varying rates. In 2021, breast cancer accounted for 2.08 million incident cases, 0.66 million deaths, and 20.25 million DALYs globally. In comparison, cervical, ovarian, and uterine cancers had lower burdens, with 0.67 million, 0.30 million, and 0.47 million incident cases, respectively. Age-standardized rates of breast, ovarian, and uterine cancers showed positive correlations with SDI, while cervical cancer exhibited a negative correlation. Attributable risk factors for breast cancer-associated deaths in 2021 included dietary risks, high body-mass index (BMI), high fasting plasma glucose, alcohol use, tobacco use, and low physical activity. Additional risk factors were unsafe sex and tobacco use for cervical cancer, high BMI and occupational risks for ovarian cancer, and high BMI for uterine cancer. Conclusions The burden of female-specific cancers has increased in recent decades, with significant demographic and regional discrepancies. These findings highlight the urgent need for targeted public health interventions to mitigate the global impact of these cancers.

Immunostaining for p16-INK4A (henceforth p16) is a sensitive and specific method for detection of high-grade cervical intraepithelial neoplasia (CIN) in women infected with human papillomavirus (HPV), but longitudinal data have not been obtained. We investigated the relation between p16 status and risk of CIN during 3 years of follow-up. Women aged 25–60 years were enrolled between June 10, 2003, and Dec 31, 2004, in a multicentre randomised trial comparing HPV testing with cytology. HPV-positive women were referred for colposcopy and, in seven of nine centres, were tested for p16 overexpression by immunostaining. If no CIN was detected, these women were followed up at yearly intervals until clearance of HPV infection. The primary endpoint was histologically confirmed CIN of grade 2 or worse (CIN of grade 2 [CIN2], CIN of grade 3 [CIN3], or invasive cervical cancer) at recruitment or during follow-up. We calculated the absolute and relative risks by p16 status at recruitment. We also calculated the longitudinal sensitivity of p16 testing. Additionally, we assessed the relative sensitivity of an alternative strategy (referral to colposcopy and follow-up of only HPV-positive, p16-positive women) versus conventional cytology in two age groups. Percentages were weighted by the inverse of the tested fraction. The trial in which this study is nested is registered, number ISRCTN81678807. Of 1042 HPV-positive women who were tested for p16 with no CIN detected during the first round of screening, 944 (91%) had further HPV tests. 793 (84%) of these 944 were followed up until detection of CIN2 or worse, HPV infection clearance, or for at least 3 years. CIN2 or worse was detected during follow-up in more p16-positive women (31 of 365, 8·8% [95% CI 5·8–11·8]) than in p16-negative women (17 of 579, 3·7% [1·9–5·4]; relative risk [RR] 2·61 [95% CI 1·49–4·59]). RR was higher in women aged 35–60 years at recruitment (3·37 [1·39–8·15]) than in those aged 25–34 years (2·15 [1·00–4·61]), but age was not a significant modifier. CIN3 or worse was detected during follow-up in more p16-positive women (16 of 365, 4·4% [2·3–6·6]) than in p16-negative women (six of 579, 1·3% [0·2–2·3]; RR 3·90 [95% CI 1·57–9·68]). Longitudinal sensitivity of p16 testing for detection of CIN3 or worse during follow-up at all ages was 77·8% (95% CI 63·9–91·6). The relative sensitivity of the alternative strategy compared with conventional cytology was 2·08 (1·13–3·56) in women aged 35–60 years and 2·86 (1·28–5·36) in those aged 25–34 years. HPV-positive, p16-negative women aged 35–60 years had a higher cumulative risk of CIN3 or worse during recruitment or follow-up (2·0%, 95% CI 0·3–3·7) than did HPV-negative women (0·01%, 0–0·04) or those who were cytologically normal (0·04%, 0·02–0·09) at recruitment. p16 overexpression is a marker for CIN2 or worse or for development of CIN2 or worse within 3 years in HPV-positive women, especially those aged 35–60 years. HPV-positive, p16-positive women need immediate colposcopy and, if the assessment is negative, annual follow-up. Immediate colposcopy can be avoided in HPV-positive, p16-negative women, who can be safely managed with repeat screening after 2–3 year intervals. European Union; Italian Ministry of Health; Regional Health Administrations of Piemonte, Tuscany, Veneto and Emilia Romagna; and Public Health Agency of Lazio Region.

The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening. The study, conducted by the \"HEllenic Real life Multicentric cErvical Screening\" (HERMES) study group, involved the recruitment of 4,009 women, aged 25-55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein. Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25-29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology). HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18 genotyping could represent a more accurate methodology for primary cervical cancer screening in comparison to liquid-based cytology, especially in older women.

Background Recent meta-analyses revealed an association between type 2 diabetes mellitus (T2DM) and cancer. The strongest relationship was demonstrated for liver and pancreatic cancer, followed by endometrial cancer. We aimed at assessing the association between T2DM and cancer specifically for Tyrolean patients. Methods We investigated cancer incidence in Tyrolean subjects with T2DM by linking the data from the Diabetes and the Cancer Registries. 5709 T2DM patients were included and the sex- and age-adjusted standardized incidence ratio (SIR) was calculated, cancer incidence in the Tyrolean population serving as the standard. Endpoints were the time at which cancer was diagnosed, death or end of the observation period (31 December 2010). Results Site-specific analyses revealed statistically significantly elevated SIRs for cancer of the pancreas (1.78, 95% CI 1.02, 2.89) and corpus (1.79, 95% CI 1.15, 2.66) for women, and cancer of the liver (2.71, 95% CI 1.65, 4.18) and pancreas (1.87, 95% 1.11, 2.96) for men. Sub-analyses performed according to the time of diabetes diagnosis revealed that SIR was highest in the first year after diabetes diagnosis, but SIR was demonstrated to be elevated in women for cancer of the liver (SIR 3.37, 95% CI 1.24, 7.34) and corpus (SIR 1.94, 95% CI 1.09, 3.20) and in men for liver (SIR 2.71, 95% CI 1.40, 4.74) in the period more than five years after diabetes diagnosis. In addition, increased risk at borderline statistical significance was observed in females for liver cancer (SIR 2.40, 95% CI 0.96, 4.94) and cervical cancer (SIR 1.81, 95% CI 0.87, 3.32) and in males for kidney cancer (SIR 1.65, 95% CI 0.99, 2.57). Conclusion This study revealed a higher risk for cancer at certain sites in Tyrolean patients with T2DM. However, it is important to interpret the results with great caution due to inherent methodological problems. Optimized care programs for patients with T2DM should be integrated into the recommended procedures for cancer screening.

Immunosuppression results in a higher incidence of cervical dysplasia compared with healthy controls. We examined the relationship between immunomodulator use and the presence of abnormal cervical histology in women with inflammatory bowel disease (IBD). Women with IBD and serial Pap smears were recruited. Patients were compared to age-, race-, and parity-matched controls. Pap smears were recorded in relation to exposure to immunomodulators. Variables included diagnosis, type and duration of immunosuppressant, and smoking. Forty patients (8 UC, 32 CD) with 134 Pap smears were included. The incidence of any abnormal Pap in a woman with IBD was 42.5%versus 7% of controls (P < 0.001). Women with IBD were more likely to have higher-grade lesions than controls (P < 0.001). Those women with a history of exposure to immunosuppression were more likely to have an abnormal Pap smear (P < 0.001) than controls. Pap smears done with > 6 months exposure to an immunosuppressant resulted in increased risk (OR 1.5, 1.2-4.1, P= 0.021). Cytopathology of abnormal lesions revealed either HPV serotype 16 or 18 in all specimens. Multivariate analysis did not reveal any differences between the groups when controlled for other variables. Women with IBD have a higher risk of an abnormal Pap smear compared with healthy controls. Patients with immunomodulator use have a higher risk of an abnormal Pap smear associated with HPV infection. Women with IBD should be included in the American College of Obstetrics and Gynecology screening guidelines for immunocompromised individuals.

Objective To evaluate the association between body composition and subsequent risk of the major gynecologic malignancies. Methods This is a prospective analysis of participants from the UK Biobank. We measured baseline body composition and confirmed cancer diagnosis through linkage to cancer and death registries. We evaluated hazard ratios (HRs) and confidence interval (CIs) with COX models adjusting for potential confounders. Results We document 1430 cases of the top three gynecologic malignancies (uterine corpus cancer 847 cases, ovarian cancer 514 cases, and cervical cancer 69 cases) from 245,084 female participants (75,307 were premenopausal and 169,777 were postmenopausal). For premenopausal women, whole body fat‐free mass (WBFFM) was associated with an increased risk of uterine corpus cancer (Adjusted HR per unit increase 1.04, 95% CI 1.02–1.06). For postmenopausal women, compared with the first quartile, the fourth quartile of WBFFM and whole body fat mass(WBFM) was associated with 2.16 (95% CI 1.49–3.13) times and 1.89 (95% CI 1.31–2.72) times of increased uterine corpus cancer risk, respectively. Regarding the distribution of body fat mass (FM)/fat‐free mass (FFM), FFM distributed in the trunk was associate with increased uterine corpus cancer risk in premenopausal (HR 1.18,95% CI 1.07–1.31) and postmenopausal women (HR 1.13,95% CI 1.09–1.18). Meanwhile, FM/FFM distributed in the limbs present an U‐shaped associations with uterine corpus cancer risk. We did not observe any association between aforementioned body composition indices with ovarian or cervical cancer. Conclusion FM is associated with an increased risk of uterine corpus cancer in postmenopausal women. Meanwhile, FFM is found to be a risk factor for uterine corpus cancer in both premenopausal and postmenopausal women. No association of body composition with ovarian or cervical cancer was observed. The aim of this study is to reveal the relationship between body composition and the risk of gynecological malignancies. In addition to finding that body fat mass(FM) is a risk factor for postmenopausal uterine corpus cancer, we also find that fat‐free mass(FFM) is a stronger risk factor for uterine corpus cancer in both premenopausal and postmenopausal women. No association of body composition with ovarian or cervical cancer was observed.

Cervical cancer is the fourth most common malignancy affecting women worldwide. The development of disease is related to high-risk human papillomavirus (hrHPV) infection. Cytology has been the most recommended triage for primary cervical (pre)cancer screening despite relatively low sensitivity. Recently, genomic DNA methylation has been proposed as an additional marker to increase sensitivity for detecting cervical precancerous lesion. This study aimed to evaluate the performance of methylation status of three tumor suppressor genes (CADM1, FAM19A4, and MAL) and HPV genotyping in detection of cytologic and histologic abnormalities in cervical cancer screening. Two hundred and sixty samples with available frozen cell pellets including 70 randomly selected cases of negative for intraepithelial lesion or malignancy (NILM)&HPV-negative, 70 randomly selected cases of NILM&HPV-positive, and 120 cytologic abnormalities & HPV-positive from a population-based cervical cancer screening program (n = 7,604) were investigated for the DNA methylation pattern of CADM1, FAM19A4, and MAL. Of 120 cytologic abnormalities & HPV-positive cases, there were 115 available histologic results. HPV52 and HPV58 were most commonly found in histologic HSIL+. The methylation levels of CADM1, FAM19A4, and MAL were elevated with the severity of cytologic abnormality which significantly increased by 3.37, 6.65 and 2 folds, respectively, in cytologic HSIL comparing with NILM. A significant increase in methylation levels of these three genes was also observed in histologic HSIL+ compared with negative histology but only CADM1 showed a significant higher methylation level than histologic LSIL. Using the ROC curve analysis, DNA methylation levels of FAM19A4 performed best in differentiating high-grade cytology (ASC-H+ from NILM/ASC-US/LSIL), followed by CADM1 and MAL. Whilst the CADM1 methylation performed best in distinguishing histologic HSIL+ from negative/LSIL with an area under the ROC curve of 0.684, followed by MAL (0.663) and FAM19A4 (0.642). Interestingly, after combining high DNA methylation levels to HPV16/18 genotypes, rates of histologic HSIL+ detection were substantially increased from 25% to 79.55% for CADM1, 77.27% for FAM19A4, and 72.73% for MAL, respectively. The rate further increased up to 95.45% when at least one of three genes had a high methylation level. This suggests a possible role of genomic DNA methylation, especially CADM1, in detecting histologic HSIL+ lesions in combination with hrHPV testing.

OBJECTIVESEastern Africa has the highest incidence and mortality rates from cervical cancer worldwide. It is important to describe the differences among women and their perceived risk of cervical cancer to determine target groups to increase cervical cancer screening. METHODSIn this cross-sectional study, we surveyed women seeking reproductive health services in Kisumu, Kenya to assess their perceived risk of cervical cancer and risk factors influencing cervical cancer screening uptake. χ statistics and t tests were used to determine significant factors, which were incorporated into a logistic model to determine factors independently associated with cervical cancer risk perception. RESULTSWhereas 91% of the surveyed women had heard of cancer, only 29% of the 388 surveyed women had previously heard of cervical cancer. Most had received their information from health care workers. Few women (6%) had ever been screened for cervical cancer and cited barriers such as fear, time, and lack of knowledge about cervical cancer. Nearly all previously screened women (22/24 [92%]) believed that cervical cancer was curable if detected early and that screening should be conducted annually (86%). Most women (254/388 [65%]) felt they were at risk for cervical cancer. Women with perceived risk of cervical cancer were older (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02–1.10), reported a history of marriage (OR, 2.08; CI, 1.00–4.30), were less likely to feel adequately informed about cervical cancer by health care providers (OR, 0.76; CI, 0.18–0.83), and more likely to intend to have cervical cancer screening in the future (OR, 10.59; CI, 3.96–28.30). Only 5% of the women reported that they would not be willing to undergo screening regardless of cost. CONCLUSIONSCervical cancer is a major health burden for women in sub-Saharan Africa, yet only one third of the women had ever heard of cervical cancer in Kisumu, Kenya. Understanding factors associated with women’s perceived risk of cervical cancer could guide future educational and clinical interventions to increase cervical cancer screening.

Background. We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial Against Cancer in Young Adults; NCT00122681). Methods. Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15-25 years) in the control arm (DNA negative at baseline for the corresponding HPV type [HPV-16: n = 8193; HPV-18: n = 8463]). Results. High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval [CI], 242-794), 204 (95% CI, 129-480), and 480 (95% CI, 250-5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively. Conclusions. Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type.

In a prospective cohort study 8466 women attending routine cervical cancer screening were recruited. Colposcopy was performed on women with any degree of atypia on cytology and/or a positive high-risk human papillomavirus (HPV)-DNA test (HC2; Hybrid Capture 2 © ), and for a randomly selected sample of 3.4% women with negative findings on both. Quality control included reviews of cytology, histology, colposcopy images and retesting of samples with polymerase chain reaction. Test diagnostic performances were based on 7908 women who had complete baseline and follow-up results. Routine histology identified 86 women with high-grade cervical intraepithelial neoplasia (CIN2+), which was confirmed by review histology in only 46 cases. Sensitivity of routine cytology for the detection of CIN2+ was 43.5%, with a specificity, positive predictive value (PPV), negative predictive value (NPV) of 98.0, 11.4 and 99.7%, respectively. Sensitivity of the HC2 test for the detection of CIN2+ was 97.8%, with a specificity, PPV and NPV, of 95.3, 10.9 and 100%, respectively. No high-grade neoplasia was detected in the randomly selected control group. A negative HPV-test result, even in combination with a positive Papanicolaou (Pap) result, virtually excluded any risk of underlying high-grade disease, but this was not the case for a negative Pap result. These data show that HPV testing is of value for the detection or exclusion of prevalent CIN in a routine cervical cancer-screening setting and could be used for further risk classification of women for follow-up management.