HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis.

Although most cervical human papillomavirus type 16 (HPV16) infections become undetectable within 1-2 years, persistent HPV16 causes half of all cervical cancers. We used a novel HPV whole-genome sequencing technique to evaluate an exceptionally large collection of 5,570 HPV16-infected case-control samples to determine whether viral genetic variation influences risk of cervical precancer and cancer. We observed thousands of unique HPV16 genomes; very few women shared the identical HPV16 sequence, which should stimulate a careful re-evaluation of the clinical implications of HPV mutation rates, transmission, clearance, and persistence. In case-control analyses, HPV16 in the controls had significantly more amino acid changing variants throughout the genome. Strikingly, E7 was devoid of variants in precancers/cancers compared to higher levels in the controls; we confirmed this in cancers from around the world. Strict conservation of the 98 amino acids of E7, which disrupts Rb function, is critical for HPV16 carcinogenesis, presenting a highly specific target for etiologic and therapeutic research.

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.

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.

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.

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.

Impact of Human Papillomavirus Vaccination, Rwanda and Bhutan.

Rwanda and Bhutan, 2 low- and middle-income countries, implemented primarily school-based national human papillomavirus (HPV) vaccination in 2011 (Rwanda) and 2010 (Bhutan). We estimated vaccination effectiveness through urine-based HPV prevalence surveys in schools in 2013-2014 and 2017. In Rwanda, 912 participants from baseline surveys and 1,087 from repeat surveys were included, and in Bhutan, 973 participants from baseline surveys and 909 from repeat surveys were included. The overall effectiveness against vaccine-targeted HPV types (i.e., HPV-6/11/16/18) was 78% (95% CI 51%-90%) in Rwanda, and 88% (6%-99%) in Bhutan and against other α-9 types was 58% (21-78) in Rwanda and 63% (27-82) in Bhutan. No effect against other HPV types was detectable. Prevalence of vaccine-targeted HPV types decreased significantly, as well as that of other α-9 types, suggesting cross-protection. These findings provide direct evidence from low- and middle-income countries of the marked effectiveness of high-coverage school-based, national HPV vaccination programs.

Prevalence of Human Papillomavirus and Estimation of Human Papillomavirus Vaccine Effectiveness in Thimphu, Bhutan, in 2011-2012 and 2018 : A Cross-sectional Study.

BACKGROUND: Bhutan implemented a national program for human papillomavirus (HPV) vaccination in 2010 involving girls aged 12 to 18 years and achieving nearly 90% coverage. OBJECTIVE: To estimate HPV vaccine effectiveness in a city in Bhutan. DESIGN: 2 cross-sectional surveys, 2011-2012 and 2018. SETTING: 2 hospitals in Thimphu, capital of Bhutan. PARTICIPANTS: Sexually active women aged 17 to 29 years: 1445 participants from the baseline survey and 1595 from the repeated survey. INTERVENTION: National HPV vaccination program. MEASUREMENTS: HPV was assessed in cervical cell samples by using general primer GP5+/GP6+-mediated polymerase chain reaction. Human papillomavirus types were stratified as vaccine types (HPV6/11/16/18) and nonvaccine types. Age- and sexual behavior-adjusted overall, total, and indirect (herd immunity) vaccine effectiveness (VE) was computed as (1 - HPV prevalence ratio) for HPV among all women and among unvaccinated women. RESULTS: Between the 2 surveys, the prevalence of HPV vaccine types decreased from 8.3% to 1.4%, whereas the prevalence of nonvaccine types increased from 25.8% to 31.4%. The overall and indirect adjusted VE against vaccine-targeted HPV types was 88% (95% CI, 80% to 92%) and 78% (CI, 61% to 88%), respectively. Among women younger than 27 years, who were targeted by the vaccination program, the overall and indirect adjusted VE was 93% (CI, 87% to 97%) and 88% (CI, 69% to 95%), respectively. No impact on nonvaccine HPV types was detectable. LIMITATION: Hospital-based recruitment; self-reported vaccination status. CONCLUSION: In Bhutan, the prevalence of vaccine-targeted HPV types has decreased sharply, providing the first evidence of the effectiveness of a high-coverage national HPV vaccination program in a lower-middle-income country. PRIMARY FUNDING SOURCE: Bill & Melinda Gates Foundation.

The disparities in gastrointestinal cancer incidence among Chinese populations in Shanghai compared to Chinese immigrants and indigenous non-Hispanic white populations in Los Angeles, USA.

Gastrointestinal cancer patterns are distinct among populations. Our study aims to compare the incidence and risk of gastrointestinal cancers between Chinese American and non-Hispanic whites in Los Angeles, CA, USA, to those of people indigenous to Shanghai to elucidate the changing patterns of gastrointestinal cancers. Cancer incidence data from 1988 to 2012 were extracted from the Cancer Incidence in Five Continents plus database. The age standardized incidence and estimated annual percentage change were calculated to estimate the temporal trends of gastrointestinal cancers. Traditional Poisson regression models and three-factor constrained Poisson regression models were applied to compare the gastrointestinal cancer risk across populations. The incidences of oesophageal, stomach, liver and gall bladder cancers were higher among indigenous Chinese residents of Shanghai than among the other two populations in Los Angeles. While the incidences of colorectal and pancreatic cancer were higher among non-Hispanic whites, Chinese American immigrants were considered to be at an intermediate level for most gastrointestinal cancers. The gender-specific gastrointestinal cancer disparities across populations, especially between Shanghai Chinese and non-Hispanic US whites, were significant regardless of age, period or cohort scale. However, the regional differences in gastrointestinal cancer rates decreased over time. Most gastrointestinal cancer patterns in Chinese American immigrants were more aligned to those of their new country of residence than to those of their original country. The disparities in gastrointestinal cancers across populations indicate that environmental factors might play a key role in cancer genesis. Shift in environmental exposures may result in significant changes in gastrointestinal cancer incidence.

Human papillomavirus genotypes in cervical and other HPV-related anogenital cancer in Rwanda, according to HIV status.

The study aim was to describe human papillomavirus (HPV)-attributable cancer burden in Rwanda, according to anogenital cancer site, HPV type, age and HIV status. Tissue specimens of cervical, vulvar, vaginal, penile and anal cancer diagnosed in 2012-2018 were retrieved from three cancer referral hospitals and tested for high-risk (HR) HPV DNA. Cervical cancer represented the majority of cases (598 of 738), of which 96.0% were HR-HPV positive. HPV-attributable fractions in other cancer sites varied from 53.1% in 81 penile, through 76.7% in 30 vulvar, 83.3% in 24 vaginal, up to 100% in 5 anal cases. HPV16 was the predominant HR-HPV type in cervical cancer (55.0%), followed by HPV18 (16.6%) and HPV45 (13.4%). HPV16 also predominated in other cancer sites (60-80% of HR-HPV-attributable fraction). For cervical cancer, type-specific prevalence varied significantly by histology (higher alpha-9 type prevalence in 509 squamous cell carcinoma vs. higher alpha-7 type prevalence in 80 adenocarcinoma), but not between 501 HIV-negative and 97 HIV-positive cases. With respect to types targeted, and/or cross-protected, by HPV vaccines, HPV16/18 accounted for 73%, HPV31/33/45/52/58 for an additional 22% and other HR-HPV types for 5%, of HPV-attributable cancer burden, with no significant difference by HIV status nor age. These data highlight the preventive potential of the ongoing national HPV vaccination program in Rwanda, and in sub-Saharan Africa as a whole. Importantly for this region, the impact of HIV on the distribution of causal HPV types was relatively minor, confirming type-specific relevance of HPV vaccines, irrespective of HIV status.

Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77-1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80-1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55-2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.

Cervical cancer risk in women living with HIV across four continents: A multicohort study.

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/µl decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

Coverage of HPV vaccination programme in Friuli Venezia Giulia Region (Northern Italy).

OBJECTIVES: to assess the completeness and timeliness of Human papillomavirus (HPV) vaccination programme in Friuli Venezia Giulia (FVG) Region (Northern Italy), notably by monitoring 2-dose coverage among girls before they turn 15 years old (referred to as "at 15") in each year between 2009 and 2018 and making a preliminary evaluation of coverage among boys at 13 years in 2016-2018. DESIGN: retrospective study. SETTING AND PARTICIPANTS: for each vaccine recipient, demographic information and history of HPV vaccine uptake from the digital FVG Vaccination Registry updated as of 31.12.2018 were extracted. Numerator data comprised all doses allocated to FVG residents. Age-specific denominators were derived from the FVG census in each examined year. Coverage estimates for the year 2018 were also provided by number of doses. MAIN OUTCOME MEASURES: coverage for a full course of HPV vaccine, defined as 2 doses in girls and boys younger than age 15 years but 3 doses in less young women. RESULTS: In FVG 52,217 females had received >=1 dose since 2008 and 12,152 males since 2015. >=2-dose coverage in girls at 15 increased from 42% in 2009 to 76% in 2015 and slightly declined afterwards (69% in 2018). In 2008, 3-dose coverage was 65%, 74%, and 59% in females aged 16-17, 18-19, and 20-26 years, respectively. In the same year, 2-dose coverage in boys at 13 years was 54%, similar to the coverage in girls at 13 years (57%). CONCLUSIONS: this paper shows the achievements of routine and catch-up HPV vaccination in FVG. While coverage in girls at 15 years of age peaked in 2015 and slightly diminished in subsequent years, the coverage in boys at 13 in 2018 had already approached the coverage in same-age girls (57%). On account of the signs of weakening in girls' coverage, campaigns in support to HPV vaccination must be repeated, especially in favour of the most cost-effective group, i.e., girls before 15 years of age. The heavy burden posed by the COVID-19 emergency on other prevention-related activities makes a better targeted use of HPV vaccination even more necessary.

Thyroid cancer "epidemic" also occurs in low- and middle-income countries.

Thyroid cancer incidence varies greatly between and within high-income countries (HICs), and overdiagnosis likely plays a major role in these differences. Yet, little is known about the situation in low- and middle-income countries (LMICs). We compare up-to-date thyroid cancer incidence and mortality at national and subnational levels. 599,851 thyroid cancer cases in subjects aged 20-74 reported in Cancer Incidence in Five Continents volume XI from 55 countries with at least 0.5 million population, aged 20-74 years, covered by population-based cancer registration, and 22,179 deaths from the WHO Mortality Database for 36 of the selected countries, over 2008-2012, were included. Age-standardized rates were computed. National incidence rates varied 50-fold. Rates were 4 times higher among women than men, with similar patterns between countries. The highest rates (>25 cases per 100,000 women) were observed in the Republic of Korea, Israel, Canada, the United States, Italy, France, and LMICs such as Turkey, Costa Rica, Brazil, and Ecuador. Incidence rates were low (<8) in a few HICs (the Netherlands, the United Kingdom, and Denmark) and lowest (3-4) in some LMICs (such as Uganda and India). Within-country incidence rates varied up to 45-fold, with the largest differences recorded between rural and urban areas in Canada (HIC) and Brazil, India, and China (LMICs). National mortality rates were very low (<2) in all countries and in both sexes, and highest in LMICs. The very high thyroid cancer incidence and low mortality rates in some LMICs also strongly suggest a major role of overdiagnosis in these countries.

Increasing risk of uterine cervical cancer among young Japanese women: Comparison of incidence trends in Japan, South Korea and Japanese-Americans between 1985 and 2012.

In Japan, cervical cancer incidence has increased since the late 1990s especially among young women, despite a decreasing trend in most developed countries. Here, we examined age, period and birth cohort trends in cervical cancer incidence rates from 1985 to 2012. Incidence rates were ascertained using three population-based cancer registries and analyzed using Joinpoint regression and age-period-cohort models. We compared the findings in Japan to trends among Japanese-Americans in the Surveillance, Epidemiology, and End Results Registries and among women in South Korea using the Korea Central Registry. Age-standardized incidence rates in Japan decreased by 1.7% per year (95% confidence interval - 3.3%, 0.0%) until 1997 and thereafter increased by 2.6% per year (1.1%, 4.2%). Incidence rates increased among women under age 50, were stable among women aged 50-54, and decreased or remained stable among women aged 55 and over. The age-standardized incidence rate ratio by birth cohort showed a U-shaped pattern with the lowest rates in women born in the late 1930s and 1940s. In comparison, women born before 1920 and after 1970 had about double the incidence. Increasing risk in recent birth cohorts was not evident in Japanese-American or South Korean women. The trends in Japan may be attributable to increasing prevalence of human papillomavirus (HPV) infection among young women. Screening and vaccination have been shown to be highly effective and would help reverse these trends.

Prevalence of human herpesviruses infections in nonmalignant tonsils: The SPLIT study.

OBJECTIVE: To assess the prevalence of all known human herpesviruses (HHV) in tonsils of an age-stratified large sample of immunocompetent children and adults. METHODS: Patients undergoing tonsillectomy for benign indications were recruited in 19 French hospitals. After resection, the entire outer surfaces of right and left half tonsils were extensively brushed. A highly sensitive species-specific multiplex assay was used to detect herpes simplex virus 1 (HSV1), HSV2, Epstein-Barr virus (EBV; types 1 and 2), and human cytomegalovirus (CMV) DNA in 688, as well as varicella zoster virus (VZV), HHV6A, HHV6B, HHV7, and Kaposi's sarcoma-associated herpesvirus (KSHV) DNA in a subset of 440 tonsil brushings. RESULTS: Overall 85% of tonsil brushing samples were infected with at least one HHV species. HHV7 and EBV were the most prevalent (≈70%), followed by HHV6B (≈50%), HSV1, CMV, VZV (≈2%), and KSHV and HSV2 (<1%), while HHV6A was not detected. EBV prevalence was significantly higher in adults than in children, whereas it was opposite for HHV6B and VZV. No difference in HHV prevalence was observed by sex. In multivariate analysis, EBV detection was associated with age greater than or equal to 15 years (prevalence ratio [PR] = 1.8; 95% confidence interval [CI]: 1.5-2.3) and marginally with tobacco smoking (PR = 1.2; 95% CI: 1.1-1.3). CONCLUSION: Differing patterns of HHV infection in tonsils in a large age-stratified population were described. This study is by far the largest available and shows that EBV, HHV6B, and HHV7 are commonly detected in the tonsils in both men and women, in contrast to other HHVs.

Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

PURPOSE: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study. METHODS: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires. RESULTS: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97-1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95-1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95-1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81-0.99), but this association was based on a sub-analysis with a small number of cancer cases. CONCLUSIONS: In this large prospective study, coffee and tea consumptions were not associated with TC risk.

Fraction and incidence of liver cancer attributable to hepatitis B and C viruses worldwide.

High-quality data on liver cancers by probable cause are scarce in many regions of the world. The United Nations recently set a goal of eliminating viral hepatitis as a major public health threat by 2030. We aimed to estimate the number of new cases of cancers attributable to hepatitis B virus (HBV) and hepatitis C virus (HCV) at a global, regional and country level, and by development status. We used data on the prevalence of HBV and HCV in hepatocellular carcinoma from a systematic review including 119,000 cases in 260 studies covering 50 countries. A statistical model was constructed to extrapolate empirical data to countries without prevalence data. Country-specific numbers of liver cancer cases attributable to HBV and HCV were calculated using data from GLOBOCAN 2012. Globally, 770,000 cases of liver cancer occurred worldwide in 2012, of which 56% (95% CI: 52-60) were attributable to HBV and 20% (95% CI: 18-22) to HCV. Currently, HBV causes approximately two out of three cases of liver cancer in less developed countries but one in four cases in more developed countries and shows a much higher degree of geographical aggregation in Eastern Asia and sub-Saharan Africa than HCV. These estimates help set priorities for liver cancer prevention. High-coverage HBV vaccination will be transformational in HBV-endemic countries but the prevention of HCV transmission and the treatment of chronic carriers of both viruses requires new scalable solutions.

Impacts of human papillomavirus vaccination for different populations: A modeling study.

International variations in the prevalence of HPV infection derive from differences in sexual behaviors, which are also a key factor of the basic reproductive number (R0 ) of HPV infection in different populations. R0 affects the strength of herd protection and hence the impact of a vaccination program. Similar vaccination programs may therefore generate different levels of impact depending upon the population's pre-vaccination HPV prevalence. We used IARC's transmission model to estimate (i) the overall effectiveness of vaccination versus no vaccination in women aged 15-34 years measured as percent prevalence reduction (%PR) of HPV16 and (ii) the corresponding herd protection in populations with gender-equal or traditional sexual behavior and with different levels of sexual activity, corresponding to pre-vaccination HPV16 prevalence from 1 to 8% as observed worldwide. Between populations with different levels of gender-equal sexual activity, the highest difference in %PR under girls-only vaccination is observed at 40% coverage (91%PR vs. 48%PR for 1% and 8% pre-vaccination prevalence, respectively). HPV16 elimination is obtained with 55 and 97% coverage, respectively. To achieve desirable levels of HPV16 prevalence after vaccination, different levels of coverage are required in populations with different levels of pre-vaccination HPV16 prevalence, for example, in populations with gender-equal sexual behavior a decrease to 1/1000 HPV16 from pre-vaccination prevalence of 1 and 8% would require coverages of 37 and 96%, respectively. In traditional populations, corresponding coverages would need to be 28 and 93%, respectively. In conclusion, pre-vaccination HPV prevalence strongly influences herd immunity and helps predict the overall effectiveness of HPV vaccination.

A case-control study of HIV infection and cancer in the era of antiretroviral therapy in Rwanda.

The aim of this study was to assess the association between HIV infection and cancer risk in Rwanda approximately a decade after the introduction of antiretroviral therapy (cART). All persons seeking cancer care at Butaro Cancer Center of Excellence (BCCOE) in Rwanda from 2012 to 2016 were routinely screened for HIV, prior to being confirmed with or without cancer (cases and controls, respectively). Cases were coded according to ICD-O-3 and converted to ICD10. Associations between individual cancer types and HIV were estimated using adjusted unconditional logistic regression. 2,656 cases and 1,196 controls differed by gender (80.3% vs. 70.8% female), age (mean 45.5 vs. 37.7 years), place of residence and proportion of diagnoses made by histopathology (87.5% vs. 67.4%). After adjustment for these variables, HIV was significantly associated with Kaposi Sarcoma (n = 60; OR = 110.3, 95%CI 46.8-259.6), non-Hodgkin lymphoma (NHL) (n = 265; OR = 2.5, 1.4-4.6), Hodgkin lymphoma (HL) (n = 76; OR = 5.2, 2.3-11.6) and cancers of the cervix (n = 560; OR = 5.9, 3.8-9.2), vulva (n = 23; OR = 17.8, 6.3-50.1), penis (n = 29; OR = 8.3, 2.5-27.4) and eye (n = 17; OR = 4.7, 1.0-25.0). Associations varied by NHL/HL subtype, with that for NHL being limited to DLBCL (n = 56; OR = 6.6, 3.1-14.1), particularly plasmablastic lymphoma (n = 6, OR = 106, 12.1-921). No significant associations were seen with other commonly diagnosed cancers, including female breast cancer (n = 559), head and neck (n = 116) and colorectal cancer (n = 106). In conclusion, in the era of cART in Rwanda, HIV is associated with increased risk of a range of infection-related cancers, and accounts for an important fraction of cancers presenting to a referral hospital.