Circulating endogenous sex steroids and risk of differentiated thyroid carcinoma in men and women.

Thyroid cancer (TC) is substantially more common in women than in men, pointing to a possible role of sex steroid hormones. We investigated the association between circulating sex steroid hormones, sex hormone binding globulin (SHBG) and the risk of differentiated TC in men and women within the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. During follow-up, we identified 333 first primary incident cases of differentiated TC (152 in pre/peri-menopausal women, 111 in post-menopausal women, and 70 in men) and 706 cancer-free controls. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre-menopausal women only) were performed using liquid chromatography/mass spectrometry method. SHBG concentrations were measured by immunoassay. Odds ratios (ORs) were estimated using conditional logistic regression models adjusted for possible confounders. No significant associations were observed in men and postmenopausal women, while a borderline significant increase in differentiated TC risk was observed with increasing testosterone (adjusted OR T3 vs T1: 1.68, 95% CI: 0.96-2.92, ptrend = .06) and androstenedione concentrations in pre/perimenopausal women (adjusted OR T3 vs T1: 1.78, 95% CI: 0.96-3.30, ptrend = .06, respectively). A borderline decrease in risk was observed for the highest progesterone/estradiol ratio (adjusted OR T3 vs T1: 0.54, 95% CI: 0.28-1.05, ptrend = .07). Overall, our results do not support a major role of circulating sex steroids in the etiology of differentiated TC in post-menopausal women and men but may suggest an involvement of altered sex steroid production in pre-menopausal women.

Association of hormonal and reproductive factors with differentiated thyroid cancer risk in women: a pooled prospective cohort analysis.

BACKGROUND: The incidence of differentiated thyroid cancer (DTC) is higher in women than in men but whether sex steroid hormones contribute to this difference remains unclear. Studies of reproductive and hormonal factors and thyroid cancer risk have provided inconsistent results. METHODS: Original data from 1 252 907 women in 16 cohorts in North America, Europe, Australia and Asia were combined to evaluate associations of DTC risk with reproductive and hormonal factors. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: During follow-up, 2142 women were diagnosed with DTC. Factors associated with higher risk of DTC included younger age at menarche (<10 vs 10-11 years; HR, 1.28; 95% CI, 1.00-1.64), younger (<40; HR, 1.31; 95% CI, 1.05-1.62) and older (≥55; HR, 1.33; 95% CI, 1.05-1.68) ages at menopause (vs 40-44 years), ever use of menopausal hormone therapy (HR, 1.16; 95% CI, 1.02-1.33) and previous hysterectomy (HR, 1.25; 95% CI, 1.13-1.39) or bilateral oophorectomy (HR, 1.14; 95% CI, 1.00-1.29). Factors associated with lower risk included longer-term use (≥5 vs <5 years) of oral contraceptives (HR, 0.86; 95% CI, 0.76-0.96) among those who ever used oral contraception and baseline post-menopausal status (HR, 0.82; 95% CI, 0.70-0.96). No associations were observed for parity, duration of menopausal hormone therapy use or lifetime number of reproductive years or ovulatory cycles. CONCLUSIONS: Our study provides some evidence linking reproductive and hormonal factors with risk of DTC. Results should be interpreted cautiously considering the modest strength of the associations and potential for exposure misclassification and detection bias. Prospective studies of pre-diagnostic circulating sex steroid hormone measurements and DTC risk may provide additional insight.

Genomic instability analysis in DNA from Papanicolaou test provides proof-of-principle early diagnosis of high-grade serous ovarian cancer.

Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples were taken at different time points (from 1 month to 13.5 years before diagnosis) from 113 presymptomatic women who were subsequently diagnosed with HGSOC (pre-HGSOC) and from 77 healthy women. Genome instability was detected through low-pass whole-genome sequencing of DNA derived from Pap test samples in terms of copy number profile abnormality (CPA). CPA values of DNA extracted from Pap test samples from pre-HGSOC women were substantially higher than those in samples from healthy women. Consistently with the longitudinal analysis of clonal pathogenic TP53 mutations, this assay could detect HGSOC presence up to 9 years before diagnosis. This finding confirms the continual shedding of tumor cells from fimbriae toward the endocervical canal, suggesting a new path for the early diagnosis of HGSOC. We integrated the CPA score into the EVA (early ovarian cancer) test, the sensitivity of which was 75% (95% CI, 64.97 to 85.79), the specificity 96% (95% CI, 88.35 to 100.00), and the accuracy 81%. This proof-of-principle study indicates that the early diagnosis of HGSOC is feasible through the analysis of genomic alterations in DNA from endocervical smears.

Acceptability of deferring the start of cervical cancer screening to age 30 for women vaccinated against human papillomavirus.

HPV vaccination of girls younger than 15 is very effective in reducing their risk of cervical cancer. In Italy, for vaccinated women, the starting age for cervical cancer screening is set to change from 25 to 30. Adherence to a protocol change is crucial to assure efficacy. The aim of our study was to monitor women's reaction to the change and learn about their attitudes. In September 2022, an anonymous online questionnaire was proposed to 3122 women born in 1997, fully vaccinated before 15 years of age and afferent to an organized cervical cancer screening programme in the Veneto region (North-East Italy). The questionnaire included 30 items on knowledge of HPV infection and preventive measures for cervical cancer, gynaecological check-ups and reactions to the deferment of the start of screening. Overall, 147 questionnaires were completed (4.7% participation rate). Almost all women had some information on HPV and HPV vaccination, while one third were unaware of the existence of the screening programme. Over 66% expressed agreement with the rationale for the deferment of screening initiation, but 62% would have preferred to start screening at 25. There was a significant association between having had one or more Pap tests and the willingness to undergo additional testing outside the screening programme before the age of 30. Continued efforts are required to improve the effectiveness of communication to women, especially when implementing existing protocols, together with strategies to promote correct approaches.

Trends in radioactive iodine treatment after total thyroidectomy in Italy, 2001-2018.

Objective: A decrease in the use of radioactive iodine (RAI) treatment for thyroid cancer has been described in the last decade in the US following subsequent updates of the American Thyroid Association guidelines. By contrast, population-based data from European countries are lacking. The study aims to assess the frequency and long-term trends in the use of RAI in Italy. Methods: From the Italian national hospital discharge database, the proportion of RAI treatment after total thyroidectomy with thyroid cancer diagnosis has been assessed by sex and age class during 2001-2018. Results: Throughout the whole study period, RAI was performed after 58% of 149,419 total thyroidectomies. The use of RAI was higher for men and younger patients; it peaked in 2007 (64% in women and 68% in men) and declined thereafter (2018: 46% in women and 53% in men), with a similar pattern observed across all ages and areas. Conclusion: National data show that in Italy trends in RAI treatment paraleled those observed in the US. Further monitoring of the use of RAI is warranted in Italy, as elsewhere, to assess the impact of international guidelines on real-life clinical management of thyroid cancer.

De-Implementation of Axillary Staging and Radiotherapy in Low-Risk Breast Cancer Patients Aged 70-79 Years from Six Italian Cancer Institutes.

In women aged ≥70 with low-risk breast cancer (BrC), some major international guidelines recommend against sentinel lymph node biopsy (for example, those from the Society of Surgical Oncology, U.S.) and post-lumpectomy radiotherapy (for example, those from the National Comprehensive Cancer Network, U.S.). We assessed the frequency of both procedures in six National Cancer Institutes (IRCCSs) in the North, the Centre, and the South of Italy. Data on tumour characteristics and treatment were obtained from each centre. Patients aged 70-79 years diagnosed with a pT1-pT2, clinically axillary lymph node-negative, oestrogen and/or progesterone receptor-positive, and human epidermal growth factor receptor 2-negative BrC between 2015 and 2020 were eligible for the study. Factors associated with the omission of the two procedures were evaluated using binary penalised logistic regression models. Axillary staging was omitted in 33/1000 (3.3%) women. After simultaneous adjustment for the centre of treatment and all other key variables, axillary staging was omitted more often in 2015-2016 vs. 2017-2020 (odds ratio (OR): 2.7; 95% CI: 1.0-7.5), in women aged 75-79 vs. 70-74 years (OR: 2.3; 95% CI: 1.1-4.9), and in those who had mastectomy vs. breast-conserving surgery (OR: 3.3; 95% CI: 1.2-9.0). The higher the histological grade was, the less frequent were the omissions (OR for grade 3 vs. grade 1: 0.2; 95% CI: 0.0-0.7). Post-lumpectomy radiotherapy was omitted in 56/651 (8.6%) women with no significant association with age, period, tumour stage, and tumour grade. In conclusion, the omission of axillary staging and post-lumpectomy radiotherapy in low-risk older BrC patients was rare in the Italian IRCCSs. Although women included in the study cannot be considered a nationally representative sample of BrC patients in Italy, our findings can serve as a baseline to monitor the impact of future guidelines. To do that, the recording and storage of hospital-based information should be improved.

Human papillomavirus vaccine effect against human papillomavirus infection in Rwanda: evidence from repeated cross-sectional cervical-cell-based surveys.

BACKGROUND: Rwanda was the first African country to implement national human papillomavirus (HPV) vaccination (against types HPV6, 11, 16, and 18). In 2011, a school-based catch-up programme was initiated to vaccinate girls aged younger than 15 years but it also reached older girls in schools. We aimed to estimate the population-level effect of HPV vaccination on HPV prevalence. METHODS: Cross-sectional surveys were done between July, 2013, and April, 2014 (baseline), and between March, 2019, and December, 2020 (repeat), in sexually active women aged 17-29 years at health centres in the Nyarugenge District of Kigali, Rwanda. HPV prevalence was assessed in cervical cell samples collected by a health-care worker in PreservCyt solution (Cytyc, Boxbourough, MA, USA) and tested using a general primer (GP5+ or GP6+)-mediated PCR. Adjusted overall, total, and indirect (herd immunity) vaccine effectiveness was computed as the percentage of HPV detection among all women and among unvaccinated women. FINDINGS: 1501 participants completed the baseline survey and 1639 completed the repeat survey. HPV vaccine-type prevalence in participants aged 17-29 years decreased from 12% (173 of 1501) in the baseline survey to 5% (89 of 1639) in the repeat survey, with an adjusted overall vaccine effectiveness of 47% (95% CI 31 to 60) and an adjusted indirect vaccine effectiveness of 32% (9 to 49). Among participants aged 17-23 years, who were eligible for catch-up vaccination, the adjusted overall vaccine effectiveness was 52% (35 to 65) and the adjusted indirect vaccine effectiveness was 36% (8 to 55), with important heterogeneity according to education (overall vaccine effectiveness was 68% [51 to 79] in participants with ≥6 years of school completed and 16% [-34 to 47] in those with <6 years) and HIV status (overall vaccine effectiveness was 55% [36 to 69] for HIV-negative participants and 24% [-62 to 64] for HIV-positive participants). INTERPRETATION: In Rwanda, the prevalence of vaccine-targeted HPV types has been significantly decreased by the HPV vaccine programme, most notably in women who were attending school during the catch-up programme in 2011. HPV vaccine coverage and population-level impact is expected to increase in future cohorts who are eligible for routine HPV vaccination at age 12 years. FUNDING: Bill & Melinda Gates Foundation.

Human papillomavirus testing on self-collected samples to detect high-grade cervical lesions in rural Bhutan: The REACH-Bhutan study.

BACKGROUND: "REACH-Bhutan" aimed to evaluate the feasibility and clinical performance of a community-based screening program for cervical cancer in rural Bhutan using self-collected samples for high-risk human papillomavirus (HR-HPV) testing. METHODS: In April/May 2016, 2590 women aged 30-60 years were screened across rural Bhutan by providing a self-collected sample for careHPV testing. All careHPV-positive women, plus a random sample of careHPV-negative women, were recalled for colposcopy and biopsy. Self-samples also underwent GP5+/6+ polymerase chain reaction (PCR)-based HR-HPV DNA detection and genotyping. Cross-sectional screening indices were estimated against histological high-grade squamous intraepithelial lesions or worse (hHSIL+), including imputation of hHSIL+ in women without colposcopy. RESULTS: HR-HPV positivity was 10.2% by careHPV and 14.8% by GP5+/6+ PCR. Twenty-two cases of hHSIL+ were histologically diagnosed, including one invasive cancer; an additional 7 hHSIL+ were imputed in women without colposcopy. HR-HPV testing by GP5+/6+ showed higher sensitivity for hHSIL+ (89.7%, 95% CI 72.6-97.8) than careHPV (75.9%, 95% CI 56.5-89.7). Negative predictive value was also slightly higher for GP5+/6+ (99.9%, 95% CI 99.6-100) than careHPV (99.7%, 95% CI 99.4-99.9). Specificity, however, was lower for GP5+/6+ (86.1%, 95% CI 84.6-87.4) than careHPV (90.6%, 95% CI 89.4-91.7), as was positive predictive value (6.9%, 95% CI 4.5-9.9 vs. 8.5%, 95% CI 5.4-12.6). Of 377 HR-HPV-positive women by GP5+/6+, 173 (45.9%) were careHPV-positive, including 54.7% HPV16-positive and 30.2% HPV18-positive women. CONCLUSIONS: The final REACH-Bhutan results show that screening for cervical cancer with self-collection of samples and HR-HPV testing, in addition to our previous report of achieving high participation, can also perform well to detect women with hHSIL+.

The use of PSA testing over more than 20 years: A population-based study in North-Eastern Italy.

OBJECTIVE: To describe the practice of prostate-specific antigen (PSA) testing over more than 20 years in Friuli Venezia Giulia (FVG), North-Eastern Italy. METHODS: A population-based, ecological study was conducted using information derived from regional administrative health-related databases. Data on PSA and prostate biopsies performed on resident men aged ⩾45 years from 1998 to 2019 were retrieved. PSA and biopsy rates were calculated as the number of men who had at least one such procedure in each calendar year over the mean resident male population of the same year. Temporal trends were analyzed using joinpoint regression (annual percentage change -APC). RESULTS: A total of 2,502,670 PSA were made between 1998 to 2019 in men aged ⩾45 years. The number of PSA steadily increased from 51,055 in 1998-1999 to 134,504 in 2010-2011, then dropped to 122,080 in 2018-2019. Significant changes in the slopes of PSA rates emerged in 2002 and 2009: the largest increase occurred during 1998-2002 (APC 18.4), followed by a smaller increase in 2002-2009 (APC 3.4) and a subsequent reduction (APC -2.5). Similar patterns emerged for all ages, but the decrease since 2009 was smaller for men aged ⩾65 years. An upward trend emerged in biopsy rate from 1998 to 2001 (APC 13.0), followed by a smaller increase until 2007 (APC 5.7) and a subsequent decrease. Biopsies as percentage of PSA decreased from 3.2% to 2.2%, particularly in those aged ⩾75 years. CONCLUSIONS: Although overall declining PSA rates have been observed in FVG since 2009, rates remained higher in the ⩾65-year-old group than in the 45-64-year-old group.

Risk factors for head and neck cancer in more and less developed countries: Analysis from the INHANCE consortium.

OBJECTIVE: We analyzed the pooled case-control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries. SUBJECTS AND METHODS: The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared. RESULTS: The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20 years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20 years conferred a higher risk for oropharynx, hypopharynx, and larynx cancer in less developed countries. The proportion of cases that were young (<45 years) or female differed by country type for some HNC subsites. CONCLUSION: These findings suggest the degree of industrialization and economic development affects the relationship between smoking and alcohol with head and neck cancer.

Age-Specific Prevalence of Anal and Cervical Human Papillomavirus Infection and High-Grade Lesions in 11 177 Women by Human Immunodeficiency Virus Status: A Collaborative Pooled Analysis of 26 Studies.

BACKGROUND: Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention. METHODS: We centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology. RESULTS: In HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+. CONCLUSIONS: Age-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

Burden of Kaposi sarcoma according to HIV status: A systematic review and global analysis.

In 2020, over 34 000 cases of Kaposi sarcoma (KS) were estimated globally, all attributable to KS herpesvirus (KSHV). Prior to the HIV epidemic, KS already existed in KSHV endemic regions, notably in sub-Saharan Africa (SSA). The HIV epidemic has vastly increased the KS burden. We developed a methodology to provide global estimates of KS burden according to HIV status. A systematic review identified studies reporting HIV prevalence in consecutive KS series. Pooled estimates of HIV prevalence, by country or UN subregion, were used to calculate population-attributable fraction (PAF) and these were applied to IARC's GLOBOCAN 2020 to estimate burden and incidence of HIV-attributable and non-HIV-attributable KS. We identified 55 eligible studies, reporting HIV prevalence ranging from ≤5% to ≥95%. Approximately 80% of KS in SSA was estimated attributable to HIV, vs ~50% in the rest of the world. By applying PAFs to national GLOBOCAN estimates, an estimated 19 560 KS cases attributable to HIV were diagnosed in SSA in 2020 (~80% of the worldwide burden), vs 5064 cases of non-HIV-attributable KS (~60% of the worldwide burden). Incidence of HIV-attributable KS was highest in Southern Africa (6.0 cases per 100 000) and Eastern Africa (3.4), which were also the world regions with highest incidence of non-HIV-attributable KS (0.4 and 1.0 cases per 100 000, respectively). This first systematic effort to produce a global picture of KS burden stratified by HIV status highlights the continuing important burden of HIV-attributable KS in SSA, even in the era of combined antiretroviral therapy.

Thyroidectomies in Italy: A Population-Based National Analysis from 2001 to 2018.

Background: The incidence of thyroid disease is generally increasing, and it is subject to major geographic variability, between and within countries. Moreover, the incidence rates and the proportion of overdiagnosis for thyroid cancer in Italy are among the highest worldwide. This study aimed to estimate population-based frequency and trends of thyroidectomies in Italy by type of surgical procedure (total/partial), indication (tumors/other conditions), sex, age, and geographical region. Materials and Methods: Age-standardized rates (ASRs) of thyroidectomies were estimated from 2001 to 2018 using the national hospital discharges database. Results: In Italy, ASRs of thyroidectomies were nearly 100 per 100,000 women in 2002-2004 and decreased to 71 per 100,000 women in 2018. No corresponding variation was shown in men (ASR 27 per 100,000 men) in the overall period. A more than twofold difference between Italian regions emerged in both sexes. The proportion of total thyroidectomies (on the sum of total and partial thyroidectomies) in the examined period increased from 78% to 86% in women and from 72% to 81% in men. Thyroidectomies for goiter and nonmalignant conditions decreased consistently throughout the period (from 81 per 100,000 women in 2002 to 49 in 2018 and from 22 to 16 per 100,000 men), while thyroidectomies for tumors increased until 2013-2014 up to 24 per 100,000 women (9 per 100,000 men) and remained essentially stable thereafter. Conclusions: The decrease in thyroidectomies for nonmalignant diseases since early 2000s in Italy may derive from the decrease of goiter prevalence, possibly as a consequence of the reduction of iodine deficiency and the adoption of conservative treatments. In a context of overdiagnosis of thyroid cancer, recent trends have suggested a decline in the diagnostic pressure with a decrease in geographic difference. Our results showed the need and also the possibility to implement more conservative surgical approaches to thyroid diseases, as recommended by international guidelines.

The relative and attributable risks of cardia and non-cardia gastric cancer associated with Helicobacter pylori infection in China: a case-cohort study.

BACKGROUND: Helicobacter pylori infection is a major cause of non-cardia gastric cancer (NCGC), but its causal role in cardia gastric cancer (CGC) is unclear. Moreover, the reported magnitude of association with NCGC varies considerably, leading to uncertainty about population-based H pylori screening and eradication strategies in high-risk settings, particularly in China, where approximately half of all global gastric cancer cases occur. Our aim was to assess the associations of H pylori infection, both overall and for individual infection biomarkers, with the risks of NCGC and CGC in Chinese adults. METHODS: A case-cohort study was done in adults from the prospective China Kadoorie Biobank study, aged 30-79 years from ten areas in China (Qingdao, Haikou, Harbin, Suzhou, Liuzhou, Henan, Sichuan, Hunan, Gansu, and Zhejiang), and included 500 incident NCGC cases, 437 incident CGC cases, and 500 subcohort participants who were cancer-free and alive within the first two years since enrolment in 2004-08. H pylori biomarkers were measured in stored baseline plasma samples using a sensitive immunoblot assay (HelicoBlot 2.1), with adapted criteria to define H pylori seropositivity. Cox regression was used to estimate adjusted hazard ratios (HRs) for NCGC and CGC associated with H pylori infection. These values were used to estimate the number of gastric cancer cases attributable to H pylori infection in China. FINDINGS: Of the 512 715 adults enrolled in the China Kadoorie Biobank between June, 2004, and July, 2008, 500 incident NCGC cases, 437 incident CGC cases, and 500 subcohort participants were selected for analysis. The seroprevalence of H pylori was 94·4% (95% CI 92·4-96·4) in NGCG, 92·2% (89·7-94·7) in CGC, and 75·6% (71·8-79·4) in subcohort participants. H pylori infection was associated with adjusted HRs of 5·94 (95% CI 3·25-10·86) for NCGC and 3·06 (1·54-6·10) for CGC. Among the seven individual infection biomarkers, cytotoxin-associated antigen had the highest HRs for both NCGC (HR 4·41, 95% CI 2·60-7·50) and CGC (2·94, 1·53-5·68). In this population, 78·5% of NCGC and 62·1% of CGC cases could be attributable to H pylori infection. H pylori infection accounted for an estimated 339 955 cases of gastric cancer in China in 2018. INTERPRETATION: Among Chinese adults, H pylori infection is common and is the cause of large numbers of gastric cancer cases. Population-based mass screening and the eradication of H pylori should be considered to reduce the burden of gastric cancer in high-risk settings. FUNDING: Cancer Research UK, Wellcome Trust, UK Medical Research Council, British Heart Foundation, Kadoorie Charitable Foundation, National Key Research and Development Program of China, and National Natural Science Foundation of China.

Risk of thyroid as a first or second primary cancer. A population-based study in Italy, 1998-2012.

BACKGROUND: The number of patients living after a cancer diagnosis is increasing, especially after thyroid cancer (TC). This study aims at evaluating both the risk of a second primary cancer (SPC) in TC patients and the risk of TC as a SPC. METHODS: We analyzed two population-based cohorts of individuals with TC or other neoplasms diagnosed between 1998 and 2012, in 28 Italian areas covered by population-based cancer registries. Standardized incidence ratios (SIRs) of SPC were stratified by sex, age, and time since first cancer. RESULTS: A total of 38,535 TC patients and 1,329,624 patients with other primary cancers were included. The overall SIR was 1.16 (95% CI: 1.12-1.21) for SPC in TC patients, though no increase was shown for people with follicular (1.06) and medullary (0.95) TC. SPC with significantly increased SIRs was bone/soft tissue (2.0), breast (1.2), prostate (1.4), kidney (2.2), and hemolymphopoietic (1.4) cancers. The overall SIR for TC as a SPC was 1.49 (95% CI: 1.42-1.55), similar for all TC subtypes, and it was significantly increased for people diagnosed with head and neck (2.1), colon-rectum (1.4), lung (1.8), melanoma (2.0), bone/soft tissue (2.8), breast (1.3), corpus uteri (1.4), prostate (1.5), kidney (3.2), central nervous system (2.3), and hemolymphopoietic (1.8) cancers. CONCLUSIONS: The increased risk of TC after many other neoplasms and of few SPC after TC questions the best way to follow-up cancer patients, avoiding overdiagnosis and overtreatment for TC and, possibly, for other malignancies.

Infection with Human Papilloma Virus (HPV) and risk of subsites within the oral cancer.

BACKGROUND: The aim of this study was to investigate the relationship between high-risk genotypes of Human Papilloma Virus (HPV) and cancer of different subsites of the oral cavity. MATERIAL AND METHODS: A pooled analysis of five studies included on the International Head and Neck Cancer Epidemiology (INHANCE) Consortium was conducted. HPV 16 and HPV 18 were considered. Adjusted odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) for HPV and each oral cavity subsites were simultaneously estimated using multinomial logistic regression models. RESULTS: The analysis included 1157 cases and 3272 controls. This study showed a slightly higher prevalence of HPV infection among oral cancer cases than controls. In particular, an increased risk of other and not otherwise specified (NOS) sites within the oral cavity, oral tongue, palate and floor of mouth cancer was observed for overall HPV16 positivity (OR = 1.66, 95 % CI: 1.01-2.72; OR = 1.97, 95 % CI: 1.36-2.85; OR = 2.48, 95 % CI: 1.50-4.11; OR = 2.71, 95 % CI: 1.06-6.95, respectively). In particular, HPV16E7 was related to cancer of floor of mouth, oral cavity NOS and palate (OR = 2.71, 95 % CI: 1.06-6.95; OR = 3.32, 95 % CI:1.53-7.19; OR = 3.34, 95 % CI:1.38-8.06). Results were inconsistent for HPV18 due to low prevalence of infection. CONCLUSION: Our study suggests that HPV16 infection may increase the risk of developing floor of mouth, gum, tongue, and palate cancers. CLINICAL RELEVANCE: Subjects with HPV infection have a higher risk of cancer from all sites of the oral cavity.

History of tonsillectomy and risk of oropharyngeal cancer.

OBJECTIVE: To investigate whether palatine tonsillectomy in youth influences the risk of oropharyngeal cancers (OPC) by assessing the association between history of tonsillectomy and risk of tonsillar, base of tongue (BOT) cancer, and other head and neck cancers (HNC). MATERIALS AND METHODS: RACKAM was a case-case study comparing frequency of tonsillectomy history in individuals diagnosed with HNC from 2013 to 2018 in 15 centers across France. History of tonsillectomy was defined using combined assessment of patients' recollections and surgeons' visualizations of tonsil area. OPC subsite-specific odds ratios (OR) of tonsillectomy were calculated using multinomial logistic regression with non-oropharyngeal HNC as reference. RESULTS: 1045 patients were included in the study. Frequency of tonsillectomy was 19.5% in patients with tonsillar cancer (N = 85), 49.3% in BOT (N = 76), 33.8% in other oropharyngeal cancers (N = 202) and 38.0% in non-oropharyngeal HNC (N = 682). History of tonsillectomy was inversely associated with tonsillar cancer (adjusted OR 0.4; 95% CI 0.2-0.8), and positively associated with BOT cancer (adjusted OR 1.8; 95% CI 1.1-3.1), but was not associated with all OPC combined (adjusted OR 1.1; 95% CI 0.8-1.4). Sensitivity analyses considering only patients' or surgeons' assessments of tonsillectomy provided comparable results. CONCLUSION: We confirm the long-term protective effect of tonsillectomy performed in youth on future risk of tonsillar cancer, and our study is the second to report a concurrent increased risk of BOT cancer. Our data suggest that tonsillectomy in youth shifts the site of the first diagnosed oropharyngeal tumor and has a limited impact on overall risk of OPC.

Thyroid cancer incidence trends by histology in 25 countries: a population-based study.

BACKGROUND: The incidence of thyroid cancer has increased in different populations worldwide in the past 30 years. We present here an overview of international trends of thyroid cancer incidence by major histological subtypes. METHODS: We did a population-based study with data for thyroid cancer incidence collected by the International Agency for Research on Cancer (IARC) for the period 1998-2012. Data were extracted from the Cancer Incidence in Five Continents plus compendium. We selected data for 25 countries that had a population of more than 2 million individuals covered by cancer registration (87 registries in total). Further criteria were that the selected registration areas had to have a proportion of unspecified thyroid cancer of less than 10% and analyses were restricted to individuals aged 20-84 years. We calculated age-specific incidence rates and age-standardised rates per 100 000 person-years for individuals aged 20 to 84 years, and assessed trends by country, sex, and major histological subtype (papillary, follicular, medullary, or anaplastic) based on absolute changes in age-standardised incidence rates between 1998-2002 and 2008-12. FINDINGS: Papillary thyroid cancer was the main contributor to overall thyroid cancer in all the studied countries, and was the only histological subtype that increased systematically in all countries, although with large variability between countries. In women, the age-standardised incidence rate of papillary thyroid cancer during 2008-12 ranged from 4·3-5·3 cases per 100 000 person-years in the Netherlands, the UK, and Denmark, to 143·3 cases per 100 000 women in South Korea. For men during the same period, the age-standardised incidence rates of papillary thyroid cancer per 100 000 person-years ranged from 1·2 cases per 100 000 in Thailand to 30·7 cases per 100 000 in South Korea. In many countries in Asia, the increase in papillary thyroid cancer rates in women was particularly pronounced after the year 2000; rates stabilised since around 2009 in the USA, Austria, Croatia, Germany, Slovenia, Spain, Lithuania, and Bulgaria. Temporal trends for follicular and medullary thyroid cancer did not show consistent patterns across countries, but slight decreases were seen for anaplastic thyroid cancer in 21 of 25 countries between 1998-2002, and 2008-12. In 2008-12, age-standardised rates for the follicular subtype ranged between 0·5 and 2·5 cases per 100 000 women (and between 0·3 and 1·5 per 100 000 men), while those for the medullary subtype were always less than 1 case per 100 000 women or men, and for anaplastic thyroid cancer less than 0·2 cases per 100 000 women or men. INTERPRETATION: In the period from 1998 to 2012, the rapid increases in thyroid cancer incidence were observed only for papillary thyroid cancer, the subtype more likely to be found in a subclinical form and therefore detected by intense scrutiny of the thyroid gland. FUNDING: French Institut National du Cancer, Italian Association for Cancer Research, Italian Ministry of Health.

Functional outcome after inpatient rehabilitation in postintensive care unit COVID-19 patients: findings and clinical implications from a real-practice retrospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is quickly spreading worldwide, with survivors that suffer functional impairments with a consequent key role of rehabilitation in this context. To date, there is a lack of findings on the role of rehabilitation in postacute COVID-19 patients. AIM: Thus, we aimed at describing the role of a patient-tailored rehabilitation plan on functional outcome in hospitalized COVID-19 patients. DESIGN: Real-practice retrospective study. SETTING: Inpatients Rehabilitation Unit. POPULATION: Postacute COVID-19 patients. METHODS: Medical records of patients referred to an Italian COVID-19 Rehabilitation Unit from March 10th, 2020 to April 30th, 2020 were collected. All patients underwent a rehabilitative (30 minutes/set, 2 times/day), aimed to improve gas exchanges, reducing dyspnoea, and improving muscle function. At the admission (T0) and at the discharge (T1), we evaluated as outcome measures: Barthel Index (BI), modified Medical Research Council Dyspnea Scale, 6-Minute Walking Test (6-MWT) and Borg Rating of Perceived Exertion (RPE) scale. We also assessed: type of respiratory supports needed, pulmonary function, coagulation and inflammation markers and length of stay (LOS) in Rehabilitation Unit. RESULTS: We included 41 postacute COVID-19 patients (25 male and 19 female), mean aged 72.15±11.07 years. Their mean LOS in the Rehabilitation Unit was 31.97±9.06 days, as 39 successfully completed the rehabilitation treatment and 2 deceased. We found statistically significant improvement in BI (84.87±15.56 vs. 43.37±26.00; P<0.0001), 6-MWT (303.37±112.18 vs. 240.0±81.31 meters; P=0.028), Borg RPE scale (12.23±2.51 vs. 16.03±2.28; P<0.0001). CONCLUSIONS: These findings suggest that postacute COVID-19 patients might beneficiate of a motor and respiratory rehabilitation treatment. However, further studies are advised to better understand long-term sequelae of the disease. CLINICAL REHABILITATION IMPACT: This study provides evidence on the role of rehabilitation COVID-19 postacute inpatients through a patient-tailored treatment.