Global evaluation of lineage-specific human papillomavirus capsid antigenicity using antibodies elicited by natural infection.

Human Papillomavirus (HPV) type variants have been classified into lineages and sublineages based upon their whole genome sequence. Here we have examined the specificity of antibodies generated following natural infection with lineage variants of oncogenic types (HPV16, 18, 31, 33, 45, 52 and 58) by testing serum samples assembled from existing archives from women residing in Africa, The Americas, Asia or Europe against representative lineage-specific pseudoviruses for each genotype. We have subjected the resulting neutralizing antibody data to antigenic clustering methods and created relational antigenic profiles for each genotype to inform the delineation of lineage-specific serotypes. For most genotypes, there was evidence of differential recognition of lineage-specific antigens and in some cases of a sufficient magnitude to suggest that some lineages should be considered antigenically distinct within their respective genotypes. These data provide compelling evidence for a degree of lineage specificity within the humoral immune response following natural infection with oncogenic HPV.

Prevalencia y determinantes de la infección por virus de papiloma humano en mujeres jóvenes de Guanacaste y Puntarenas, Costa Rica, 2004-2005.

OBJETIVO: Estimar la prevalencia e identificar determinantes de la infección por el virus del papiloma humano (VPH) en mujeres jóvenes (18-25 años). Material y métodos. Se analizaron datos de 5 871 mujeres sexualmente activas a quienes se les realizó una entrevista y toma de muestras cervicouterinas para detección de VPH y citología durante la visita de reclutamiento del Ensayo de Vacunación contra VPH16/18 en Costa Rica. Se calculó la prevalencia total para cualquier tipo de VPH y tipos oncogénicos, no oncogénicos y específicos, con intervalos de confianza al 95% (IC95%). Se utilizó regresión logística múltiple paso-a-paso para identificar determinantes asociados con la infección. RESULTADOS: La prevalencia total de VPH fue 50.0% (IC95% 48.8,51.3) y por tipos oncogénicos fue 33.8% (IC95% 32.6,35.0). El VPH-16 fue el tipo más prevalente (8.3%, IC95% 7.6,9.0). Los determinantes asociados con un alto riesgo de infección prevalente por VPH oncogénicos fueron no estar casada/unión libre, >1 compañero sexual, infección concomitante por Chlamydia trachomatis, y entre aquéllas con un único compañero sexual en su vida, un compañero con antecedente de múltiples compañeras sexuales. Conclusión. Se confirma la asociación de las infecciones por VPH oncogénicos con el comportamiento sexual de la mujer y se destacan los comportamientos del compañero sexual.

State-of-the-Science of human papillomavirus vaccination in women with human immunodeficiency Virus: Summary of a scientific workshop.

The burden of cervical cancer is disproportionately distributed globally, with the vast majority of cases occurring in low- and middle-income countries. Women with human immunodeficiency virus (HIV) (WWH) are at increased risk of human papillomavirus (HPV) infection and cervical cancer as compared to HIV-negative individuals. HPV vaccination remains a priority in regions with a high burden of cervical cancer and high HIV prevalence. With HPV vaccines becoming more accessible, optimal use beyond the initial World Health Organization-recommended target population of 9 to 14-year-old girls is an important question. In March 2022, a group of experts in epidemiology, immunology, and vaccinology convened to discuss the state-of-the-science of HPV vaccination in WWH. This report summarizes the proceedings: review of HIV epidemiology and its intersection with cervical cancer burden, immunology, HPV vaccination including reduced-dose schedules and experience with other vaccines in people with HIV (PWH), HPV vaccination strategies and knowledge gaps, and outstanding research questions. Studies of HPV vaccine effectiveness among WWH, including duration of protection, are limited. Until data from ongoing research is available, the current recommendation for WWH remains for a multi-dose HPV vaccination regimen. A focus of the discussion included the potential impact of HIV acquisition following HPV vaccination. With no data currently existing for HPV vaccines and limited information from non-HPV vaccines, this question requires further research. Implementation research on optimal HPV vaccine delivery approaches for WWH and other priority populations is also urgently needed.

Trends in incidence rates of head and neck squamous cell carcinomas overall and by potential relatedness to human papillomavirus, Costa Rica 2006 to 2015.

In Costa Rica (CR), only one report on head and neck cancer (HNC) incidence trends (1985-2007) has been published and no investigations on the epidemiology of potentially human papillomavirus (HPV)-related and HPV-unrelated HNCs have been done. We examined the age-standardized incidence rates (IRs) and trends of head and neck squamous cell carcinomas (HNSCC) and compared incidence trends of potentially HPV-related and HPV-unrelated HNSCCs. We obtained all available HNC cases for the period 2006-2015 from the Costa Rican National Cancer Registry of Tumors and the population estimates from the Costa Rican National Institute of Statistics and Census. The analysis was restricted to invasive HNSCCs (n = 1577). IRs and incidence rate ratios were calculated using SEER*Stat software and were age-standardized for the 2010 Costa Rican population. Joinpoint regression analysis program was used to calculate trends and annual percent changes (APCs) in rates. For all HNSCCs, the age-standardized IR was 34.0/million person-years; 95% CI 32.4, 35.8. There was a significant decline in the incidence of nasopharyngeal cancer (APC: -5.9% per year; 95% CI -10.8, -0.7) and laryngeal cancer (APC: -5.4% per year; -9.2, 1.5). The incidence trends for hypopharyngeal, oropharyngeal and oral cavity cancers each remained stable over time. HNSCCs were categorized by their potential relatedness to HPV infection. Though the APCs were not statistically significant, IRs of potentially HPV-related HNSCCs trended upward, while HPV-unrelated HNSCCs trended downward. HNSCCs are uncommon in CR and decreased over time. We observed a divergent pattern of decreasing HPV-unrelated with increasing HPV-related HNSCCs that should be further informed by HPV genotyping tumor samples.

Analysis of cervical HPV infections among unvaccinated young adult women to inform vaccine strategies in this age group: the Costa Rica HPV Vaccine Trial.

INTRODUCTION: Human papillomavirus (HPV) vaccines protect against incident HPV infections, which cause cervical cancer. OBJECTIVES: We estimated the prevalence and incidence of HPV infections in young adult women to understand the impact of an HPV vaccination programme in this population. METHODS: We collected cervical specimens from 6322 unvaccinated women, aged 18-37 years, who participated in the Costa Rica Vaccine Trial and its long-term follow-up. Women were followed for (median) 4.8 years and had (median) 4.0 study visits. Cervical specimens were tested for the presence/absence of 25 HPV genotypes. For each age band, we estimated the percentage of women with 1+ prevalent or 1+ incident HPV infections using generalised estimating equations. We also estimated the prevalence and incidence of HPV as a function of time since first sexual intercourse (FSI). RESULTS: The model estimated HPV incident infections peaked at 28.0% (95% CI 25.3% to 30.9%) at age 20 years then steadily declined to 11.8% (95% CI 7.6% to 17.8%) at age 37 years. Incident oncogenic HPV infections (HPV16/18/31/33/35/39/45/51/52/56/58/59) peaked and then declined from 20.3% (95% CI 17.9% to 22.9%) to 7.7% (95% CI 4.4% to 13.1%); HPV16/18 declined from 6.4% (95% CI 5.1% to 8.1%) to 1.1% (95% CI 0.33% to 3.6%) and HPV31/33/45/52/58 declined from 11.0% (95% CI 9.3% to 13.1%) to 4.5% (95% CI 2.2% to 8.9%) over the same ages. The percentage of women with 1+ incident HPV of any, oncogenic, non-oncogenic and vaccine-preventable (HPV16/18, HPV31/33/45, HPV31/33/45/52/58, and HPV6/11) types peaked <1 year after FSI and steadily declined with increasing time since FSI (p for trends <0.001). We observed similar patterns for model estimated HPV prevalences. CONCLUSION: Young adult women may benefit from HPV vaccination if newly acquired vaccine-preventable oncogenic infections lead to cervical precancer and cancer. HPV vaccination targeting this population may provide additional opportunities for primary prevention. TRIAL REGISTRATION NUMBER: NCT00128661.

Precancerous cervical lesions caused by non-vaccine-preventable HPV types after vaccination with the bivalent AS04-adjuvanted HPV vaccine: an analysis of the long-term follow-up study from the randomised Costa Rica HPV Vaccine Trial.

BACKGROUND: In women vaccinated against human papillomavirus (HPV), reductions in cervical disease and related procedures results in more women having intact transformation zones, potentially increasing the risk of cervical lesions caused by non-vaccine-preventable HPV types, a phenomenon termed clinical unmasking. We aimed to evaluate HPV vaccine efficacy against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and cervical intraepithelial neoplasia grade 3 or worse (CIN3+) attributed to non-preventable HPV types in the long-term follow-up phase of the Costa Rica HPV Vaccine Trial (CVT). METHODS: CVT was a randomised, double-blind, community-based trial done in Costa Rica. Eligible participants were women aged 18-25 years who were in general good health. Participants were randomly assigned (1:1) to receive an HPV 16 and 18 AS04-adjuvanted vaccine or control hepatitis A vaccine, using a blocked randomisation method (permuted block sizes of 14, 16, and 18). Vaccines in both groups were administered intramuscularly with 0·5 mL doses at 0, 1, and 6 months. Masking of vaccine allocation was maintained throughout the 4-year randomised trial phase, after which participants in the hepatitis A virus vaccine control group were provided the HPV vaccine and exited the study; a screening-only, unvaccinated control group was enrolled. The unvaccinated control group and HPV vaccine group were followed up for 7 years, during which treatment allocation was not masked. One of the prespecified primary endpoints for the long-term follow-up phase was precancers associated with HPV types not prevented by the vaccine, defined as histologically confirmed incident CIN2+ events or CIN3+ events attributed to any HPV type except HPV 16, 18, 31, 33, and 45. Our primary analytical period was years 7-11. Primary analyses were in all participants with at least one follow-up visit and excluded participants with a previous endpoint (ie, modified intention-to-treat cohort). Safety endpoints have been reported elsewhere. This trial is registered with ClinicalTrials.gov, NCT00128661 and NCT00867464. The randomised, masked trial phase is completed; an unmasked subset of women in the HPV-vaccinated group is under active investigation. FINDINGS: Between June 28, 2004, and Dec 21, 2005, 7466 participants were enrolled (HPV vaccine group n=3727 and hepatitis A virus vaccine control group n=3739). Between March 30, 2009, and July 5, 2012, 2836 women enrolled in the new unvaccinated control group. The primary analytical cohort (years 7 to 11) included 2767 participants in the HPV vaccine group and 2563 in the unvaccinated group for the CIN2+ events endpoint assessment and 2826 participants in the HPV vaccine group and 2592 in the unvaccinated control group for the CIN3+ events endpoint assessment. Median follow-up during years 7 to 11 for women included for the CIN2+ events analysis was 52·8 months (IQR 44·0 to 60·7) for the HPV vaccine group and 49·8 months (42·0 to 56·9) for the unvaccinated control group. During years 7 to 11, clinical unmasking was observed with a negative vaccine efficacy against CIN2+ events attributed to non-preventable HPV types (-71·2% [95% CI -164·0 to -12·5]), with 9·2 (95% CI 2·1 to 15·6) additional CIN2+ events attributed to non-preventable HPV types per 1000 HPV-vaccinated participants versus HPV-unvaccinated participants. 27·0 (95% CI 14·2 to 39·9) fewer CIN2+ events irrespective of HPV type per 1000 vaccinated participants were observed during 11 years of follow-up. Vaccine efficacy against CIN3+ events attributed to non-preventable HPV types during years 7 to 11 was -135·0% (95% CI -329·8 to -33·5), with 8·3 (3·0 to 12·8) additional CIN3+ events attributed to non-preventable HPV types per 1000 vaccinated participants versus unvaccinated participants. INTERPRETATION: Higher rates of CIN2+ events and CIN3+ events due to non-preventable HPV types in vaccinated versus unvaccinated participants suggests clinical unmasking could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programmes in screened populations. Importantly, the net benefit of vaccination remains considerable; therefore, HPV vaccination should still be prioritised as primary prevention for cervical cancer. FUNDING: National Cancer Institute and National Institutes of Health Office of Research on Women's Health. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

HPV16 infection decreases vaccine-induced HPV16 antibody avidity: the CVT trial.

The HPV vaccine has shown sustained efficacy and consistent stabilization of antibody levels, even after a single dose. We defined the HPV16-VLP antibody avidity patterns over 11 years among women who received one- or three doses of the bivalent HPV vaccine in the Costa Rica HPV Vaccine Trial. Absolute HPV16 avidity was lower in women who received one compared to three doses, although the patterns were similar (increased in years 2 and 3 and remained stable over the remaining 8 years). HPV16 avidity among women who were HPV16-seropositive women at HPV vaccination, a marker of natural immune response to HPV16 infection, was significantly lower than those of HPV16-seronegative women, a difference that was more pronounced among one-dose recipients. No differences in HPV16 avidity were observed by HPV18 serostatus at vaccination, confirming the specificity of the findings. Importantly, point estimates for vaccine efficacy against incident, six-month persistent HPV16 infections was similar between women who were HPV16 seronegative and seropositive at the time of initial HPV vaccination for both one-dose and three-dose participants. It is therefore likely that this lower avidity level is still sufficient to enable antibody-mediated protection. It is encouraging for long-term HPV-vaccine protection that HPV16 antibody avidity was maintained for over a decade, even after a single dose.

Rationale and design of a double-blind randomized non-inferiority clinical trial to evaluate one or two doses of vaccine against human papillomavirus including an epidemiologic survey to estimate vaccine efficacy: The Costa Rica ESCUDDO trial.

HPV vaccination of adolescent girls is the most effective measure to prevent cervical cancer. The World Health Organization recommends that adolescent girls receive two doses of vaccine but only a small proportion of girls from regions with the highest disease burden are vaccinated because of cost and logistical considerations. Our Costa Rica HPV Vaccine trial suggested that one dose of the bivalent HPV vaccine provides robust and lasting protection against persistent HPV infections for over a decade. Data from a post-licensure trial of the quadrivalent vaccine in India also suggested that a single dose may be effective in reducing cervical cancer risk. To formally compare one versus two doses of the bivalent and nonavalent HPV vaccines, we implemented a large, randomized, double-blind trial to investigate the non-inferiority of one compared to two vaccine doses in the prevention of new HPV16/18 infections that persist 6 or more months. Bivalent and nonavalent vaccines will be evaluated separately. The trial enrolled and randomized (1:1:1:1 to 1- and 2-dose arms of the bivalent and nonavalent vaccines) 20,330 girls 12 to 16 years old residing in Costa Rica. Trial participants are followed every 6 months for up to 5 years. We also aim to estimate vaccine efficacy by comparing the rates of 6 month persistent infection in unvaccinated women with the rates in the follow-up visits of trial participants. We included one survey of unvaccinated women at the start of the study (N = 4452) and will include another survey concomitant with follow up visits of trial participants at year 4.5 (planned N = 3000). Survey participants attend two visits 6 months appart. Herein, we present the rationale, design, and enrolled study population of the ESCUDDO trial. ClinicalTrials.gov Identifier: NCT03180034.

Risk Factors for Non-Human Papillomavirus (HPV) Type 16/18 Cervical Infections and Associated Lesions Among HPV DNA-Negative Women Vaccinated Against HPV-16/18 in the Costa Rica Vaccine Trial.

BACKGROUND: Factors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood. We evaluated co-factors for acquisition, persistence, and progression of non-HPV-16/18 infections among HPV-vaccinated women. METHODS: We analyzed 2153 women aged 18-25 years randomized to the HPV-vaccine arm of the Costa Rica HPV Vaccine Trial. Women were HPV DNA negative for all types at baseline and followed for approximately 11 years. Generalized estimating equation methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonally related factors, number of full-term pregnancies (FTPs), smoking behavior, and baseline body mass index. RESULTS: A total of 1777 incident oncogenic non-HPV-16/18 infections were detected in 12 292 visits (average, 0.14 infections/visit). Age and sexual behavior-related variables were associated with oncogenic non-HPV-16/18 acquisition. Twenty-six percent of incident infections persisted for ≥1 year. None of the factors evaluated were statistically associated with persistence of oncogenic non-HPV-16/18 infections. Risk of progression to Cervical Intraepithelial Neoplasia grade 2 or worst (CIN2+) increased with increasing age (P for trend = .001), injectable contraceptive use (relative risk, 2.61 [95% confidence interval, 1.19-5.73] ever vs never), and increasing FTPs (P for trend = .034). CONCLUSIONS: In a cohort of HPV-16/18-vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non-HPV-16/18 infections; no notable factors are associated with persistence of acquired infections; and age, parity, and hormonally related exposures are associated with progression to CIN2+.

Evaluation of serological assays to monitor antibody responses to single-dose HPV vaccines.

INTRODUCTION: Whether existing serological assays are sufficiently robust to measure the lower antibody levels expected following single-dose HPV vaccination is unknown. METHODS: We evaluated seven assays measuring HPV-16/18 immunological responses overall and by number of doses in 530 serum samples from participants receiving varying doses of Cervarix or Gardasil up to 36-months post-vaccination. Serum was evaluated by simplex (HPV-16 ELISA, HPV-18 ELISA), multiplex (LIA-4, VLP-MIA, M9ELISA, GST-L1), and high-throughput pseudovirion-based neutralization assays (HT-PBNA), and results were compared to the gold standard HPV-16/18 secreted alkaline phosphatase neutralization assay (SEAP-NA). Reproducibility was assessed by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Percent agreement, Pearson correlation, and weighted-kappa were used to assess validity. Determinants of seronegativity were evaluated by chi-squared test. RESULTS: HPV-16: Seropositivity range was 97.1-99.5% for single dose and 98.8-99.8% overall. CV range was 4.0-18.0% for single dose and 2.9-19.5% overall. ICC range was 0.77-0.99 for single dose and 0.74-0.99 overall. Correlation with SEAP-NA range was 0.43-0.85 for single dose and 0.51-0.90 overall. Weighted-kappa range was 0.34-0.82 for single dose and 0.45-0.84 overall. HPV-18: Seropositivity range was 63.9-94.7% for single dose and 86.2-97.9% overall. CV range was 8.1-18.2% for single dose and 4.6-18.6% overall. ICC range was 0.75-0.99 for single dose and 0.83-0.99 overall. Correlation with SEAP-NA range was 0.31-0.99 for single dose and 0.27-0.96 overall. Weighted-kappa range was 0.35-0.83 for single dose and 0.45-0.84 overall. HPV-16 seronegativity was <5% for all assays. HPV-18 seronegativity range was 5.5-17.3%. For LIA-4 and GST-L1 where the proportion of seronegativity was >10%, the strongest correlates of seronegativity were receiving a single vaccine dose and receiving Gardasil. CONCLUSIONS: These results support the utility of existing serological assays to monitor antibody responses following single-dose HPV vaccination.

Evaluation of Durability of a Single Dose of the Bivalent HPV Vaccine: The CVT Trial.

BACKGROUND: The authors investigated the durability of vaccine efficacy (VE) against human papillomavirus (HPV)16 or 18 infections and antibody response among nonrandomly assigned women who received a single dose of the bivalent HPV vaccine compared with women who received multiple doses and unvaccinated women. METHODS: HPV infections were compared between HPV16 or 18-vaccinated women aged 18 to 25 years who received one (N = 112), two (N = 62), or three (N = 1365) doses, and age- and geography-matched unvaccinated women (N = 1783) in the long-term follow-up of the Costa Rica HPV Vaccine Trial. Cervical HPV infections were measured at two study visits, approximately 9 and 11 years after initial HPV vaccination, using National Cancer Institute next-generation sequencing TypeSeq1 assay. VE and 95% confidence intervals (CIs) were estimated. HPV16 or 18 antibody levels were measured in all one- and two-dose women, and a subset of three-dose women, using a virus-like particle-based enzyme-linked immunosorbent assay (n = 448). RESULTS: Median follow-up for the HPV-vaccinated group was 11.3 years (interquartile range = 10.9-11.7 years) and did not vary by dose group. VE against prevalent HPV16 or 18 infection was 80.2% (95% CI = 70.7% to 87.0%) among three-dose, 83.8% (95% CI = 19.5% to 99.2%) among two-dose, and 82.1% (95% CI = 40.2% to 97.0%) among single-dose women. HPV16 or 18 antibody levels did not qualitatively decline between years four and 11 regardless of the number of doses given, although one-dose titers continue to be statistically significantly lower compared with two- and three-dose titers. CONCLUSION: More than a decade after HPV vaccination, single-dose VE against HPV16 or 18 infection remained high and HPV16 or 18 antibodies remained stable. A single dose of bivalent HPV vaccine may induce sufficiently durable protection that obviates the need for more doses.

Global patterns and trends in colorectal cancer incidence and mortality.

OBJECTIVE: The global burden of colorectal cancer (CRC) is expected to increase by 60% to more than 2.2 million new cases and 1.1 million deaths by 2030. In this study, we aim to describe the recent CRC incidence and mortality patterns and trends linking the findings to the prospects of reducing the burden through cancer prevention and care. DESIGN: Estimates of sex-specific CRC incidence and mortality rates in 2012 were extracted from the GLOBOCAN database. Temporal patterns were assessed for 37 countries using data from Cancer Incidence in Five Continents (CI5) volumes I-X and the WHO mortality database. Trends were assessed via the annual percentage change using joinpoint regression and discussed in relation to human development levels. RESULTS: CRC incidence and mortality rates vary up to 10-fold worldwide, with distinct gradients across human development levels, pointing towards widening disparities and an increasing burden in countries in transition. Generally, CRC incidence and mortality rates are still rising rapidly in many low-income and middle-income countries; stabilising or decreasing trends tend to be seen in highly developed countries where rates remain among the highest in the world. CONCLUSIONS: Patterns and trends in CRC incidence and mortality correlate with present human development levels and their incremental changes might reflect the adoption of more western lifestyles. Targeted resource-dependent interventions, including primary prevention in low-income, supplemented with early detection in high-income settings, are needed to reduce the number of patients with CRC in future decades.

Cancer in Central and South America: Methodology.

Statistics on cancer incidence from Central and South American countries are scarce because of the small number of population-based cancer registries that continuously collect data. Similarly, comparable statistics on cancer mortality are sparse in spite of efforts made to improve coverage in the last decade. The aim of this study is to describe geographical patterns and trends in cancer incidence and mortality in Central and South America in the 21st century. The primary objective was to obtain the best quality cancer data available from each country within the region. Cancer incidence data were obtained from population-based cancer registries within the region and, in countries where these did not exist, from hospital-based registries; national mortality data were obtained from the World Health Organization mortality database. Given the variability in data quality - mainly due to the age and development in maturity of the registries, an exhaustive review of the data was necessary in order to appropriately analyze, describe and interpret patterns of cancer incidence and mortality between countries and within cancer-specific sites. This paper presents the methods employed in the collection, quality control and analysis of the datasets received for the project.

Female breast cancer in Central and South America.

RATIONALE AND OBJECTIVE: The burden of breast cancer has increased worldwide. Breast cancer mortality has been increasing in Central and South America (CSA) in the last few decades. We describe the current burden of breast cancer in CSA and review the current status of disease control. METHODS: We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries and cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence and mortality rates per 100,000 person-years for 2003-2007 and the estimated annual percentage change to describe time trends. RESULTS: In the most recent 5-year period, Argentina, Brazil, and Uruguay had the highest incidence rates (67.7-71.9) and Bolivia and El Salvador had the lowest (7.9-12.7). For most countries, mortality rates were ≤12.3, except in Uruguay, Argentina and Cuba (14.9-20.5). Age-specific rates increased after the age of 40-50 years and reached a maximum after age 65 years (mean age at diagnosis 56-62 years). Most countries have developed national screening guidelines; however, there is limited capacity for screening. CONCLUSION: The geographic variation of breast cancer rates may be explained by differences in the prevalence of reproductive patterns, lifestyle factors, early detection, and healthcare access. Extending early-detection programs is challenging because of inequalities in healthcare access and coverage, limited funding, and inadequate infrastructure, and thus it may not be feasible. Given the current status of breast cancer in CSA, data generated by population-based cancer registries is urgently needed for effective planning for cancer control.

Prostate cancer burden in Central and South America.

RATIONALE AND OBJECTIVE: The incidence of prostate cancer has increased in Central and South America (CSA) in the last few decades. We describe the geographical patterns and trends of prostate cancer in CSA. METHODS: We obtained regional and national-level cancer incidence data from 48 population-based registries in 13 countries and nation-wide cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence (ASR) and mortality (ASMR) rates per 100,000 person-years for 2003-2007 and the estimated annual percent change (EAPC) to describe time trends. RESULTS: Prostate cancer was the most common cancer diagnosis and one of the leading causes of cancer deaths among males in most CSA countries. From 2003-2007, ASRs varied between countries (6-fold) and within countries (Brazil: 3-6-fold). French Guyana (147.1) and Brazil (91.4) had the highest ASRs whereas Mexico (28.9) and Cuba (24.3) had the lowest. ASMRs varied by 4-fold. Belize, Uruguay and Cuba (24.1-28.9) had the highest ASMRs while Peru, Nicaragua, and El Salvador (6.8-9.7) had the lowest. In Argentina, Brazil, Chile and Costa Rica prostate cancer incidence increased by 2.8-4.8% annually whereas mortality remained stable between 1997 and 2008. CONCLUSION: The geographic and temporal variation of prostate cancer rates observed in CSA may in part reflect differences in diagnostic and registration practices, healthcare access, treatment and death certification, and public awareness. The incidence of prostate cancer is expected to increase given recent early detection activities and increased public awareness; however, the impact of these factors on mortality remains to be elucidated.

Cervical cancer in Central and South America: Burden of disease and status of disease control.

RATIONALE AND OBJECTIVE: More than 20 years after cytology-based screening was introduced in Central and South America (CSA), cervical cancer remains a leading cause of cancer incidence and mortality in the region. Although several population-based registries exist in the region, few comprehensive analyses have been conducted to describe the status of cervical cancer control. METHODS: Population-based data from cancer registries in 13 countries and mortality data from 18 countries in CSA were analyzed. Standardized incidence and mortality rates were estimated and time trend analysis performed when information was available. In addition, a search of available data on HPV vaccination and cervical cancer screening was carried out. RESULTS: Cervical cancer incidence and mortality have decreased in some CSA countries, with an annual percentage change from -4.2 to -6.7 for incidence and -0.2 to -8.3 for mortality. In total, seven countries have age-standardized mortality rates over 10 per 100,000 women, generally corresponding to those with the lowest income levels. All countries have implemented screening programs with different extents of coverage and levels of organization. To date, nine countries have introduced HPV vaccination in national immunization programs. CONCLUSIONS: Despite incidence declines observed in some countries, cervical cancer mortality remained almost stable in most countries in the region. Decreases in mortality trends in Chile and Costa Rica are probably the result of early detection programs. Better organized programs might favor greater impact on cancer incidence and mortality, but technological developments offer more suitable opportunities for prevention and alternative approaches for screening of precancerous lesions.

Descriptive epidemiology of brain and central nervous system cancers in Central and South America.

RATIONALE AND OBJECTIVE: Although malignant tumors of the brain and central nervous system (CNS) represent less than 3% of new cancer cases estimated worldwide, they cause significant morbidity and in the case of gliomas, the most common histological type, have a poor prognosis. We describe patterns and trends in brain and CNS incidence and mortality in Central and South America. METHODS: We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries and cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence rates (ASRs) and mortality rates (ASMRs) per 100,000 person-years, and present incidence by histological subtypes. RESULTS: In general, incidence rates were higher in males than in females. The highest incidence ASRs were observed for Cuba (5.1 males, 3.6 females) in Central America, and for Brazil (6.4 males, 4.8 females) and Uruguay (6.2 and 4.0) in South America. Mortality rates closely followed the pattern of incidence rates. Argentina, Brazil and Chile showed increasing mortality trends, although these were not statistically significant. Glioma and unspecified tumors were the most common histological types, accounting for 55.4% and 32.8%, respectively. The proportion of microscopically verified diagnoses was 47-70% in most countries. CONCLUSION: Although incidence and mortality rates in general were low, some countries displayed high- to intermediate-level incidence rates; under-reporting and under-ascertainment of cases could contribute to the geographic variations observed. There is a need to improve both the ascertainment of cases and the accuracy of histological diagnosis. Monitoring of brain and CNS cancers along with etiological research remain priorities.

Thyroid cancer burden in Central and South America.

RATIONALE AND OBJECTIVE: Incidence of thyroid cancer (TC) is rapidly increasing worldwide, but little is known about the TC burden in Central and South America (CSA). We describe the geographic patterns and trends of TC by sex in CSA. METHODS: We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries and nationwide cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence rates (ASRs) and age-standardized mortality rates (ASMRs) per 100,000 person-years. We calculated ASRs by histological subtype. We estimated the annual percentage change (EAPC) to describe time trends. RESULTS: Between CSA countries, TC incidence and mortality rates varied from 8-fold to 12-fold and from 2-fold to 5-fold, respectively. In 2003-2007, the highest TC ASRs in females and males were in Ecuador (16.0 and 3.5, respectively), Brazil (14.4 and 3.4), Costa Rica (12.6 and 2.1) and Colombia (10.7 and 2.5). The highest ASMRs were in Ecuador, Colombia, Mexico, Peru and Panama (0.68-0.91 in females and 0.41-0.48 in males). Papillary TC was the most commonly diagnosed histological subtype, following the same incidence pattern as overall TC. In Argentinean, Brazilian, Chilean and Costa Rican females TC incidence increased by 2.2-17.9% annually, and papillary TC increased by 9.1-15.0% annually, while mortality remained stable between 1997 and 2008. In males, trends in TC were stable. CONCLUSION: TC occurred more frequently in females than in males. The overall high incidence and low mortality of TC suggest identification of subclinical disease due to improved detection methods.

Hodgkin lymphoma burden in Central and South America.

RATIONALE AND OBJECTIVE: Hodgkin lymphoma (HL) is largely curable owing to improvements in treatment since the 1960s; nevertheless, high mortality rates have been reported in Central and South America. We describe the current burden of HL in the Central and South American region. METHODS: We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries, and national-level mortality data from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence rates (ASRs) and age-standardized mortality rates (ASMRs) per 100,000 person-years for 2003-2007 and present distributions by histological subtype. RESULTS: HL incidence rates varied 7-fold in males and 11-fold in females (male-to-female ratio 1:1-2.5:1). The highest ASRs were seen Argentina, Brazil, Costa Rica (males), Cuba (males) and Uruguay (females), whereas the lowest were in Bolivia and El Salvador. ASMRs varied by 4-fold in males and 6-fold in females (male-to-female ratio 1:1-4.3:1), with ASMRs <0.7 for most countries, except Cuba (≥1.0). In most countries, age-specific incidence rates of HL showed a bimodal pattern. Trends in HL in Argentina, Brazil, Chile, and Costa Rica remained stable in 1997-2008. Of all HL cases, 48% were unspecified as to histological subtype. Nodular sclerosis and mixed cellularity were the most frequent histologies. CONCLUSION: The geographic variation in HL across the region may in part reflect differences in data quality and coverage, and differences in the adoption of modern therapies and healthcare access. Our results highlight the need for high-quality data and increased coverage in order to provide vital guidance for future cancer control activities.

The burden of non-Hodgkin lymphoma in Central and South America.

RATIONALE AND OBJECTIVE: The burden of non-Hodgkin lymphoma (NHL) has increased in some Central and South American countries. We describe the current patterns and trends in NHL incidence and mortality in Central and South America. METHODS: We obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries, and national-level cancer mortality data from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence rates (ASRs) and mortality rates (ASMRs) per 100,000 person-years for 2003-2007, and presented distributions by histological subtype. RESULTS: NHL incidence and mortality rates varied between countries by 2-8- and 6-fold, respectively. ASRs per 100,000 ranged from 1.4 to 10.9 among males and 1.3-9.2 among females. Corresponding ASMRs were between 0.5 and 4.8 among males and between 0.5 and 3.0 among females. The highest incidence was observed in Uruguay (males), Ecuador, Peru and Colombia (males). The highest mortality was seen in Uruguay and Costa Rica. Trends in NHL incidence and mortality in Argentina, Brazil, Chile and Costa Rica did not show marked changes. B-cell neoplasms and NHL not otherwise specified (NOS) accounted for 44% and 34% of all NHL cases. Diffuse large B-cell lymphoma, NOS, was the most frequent histological subtype. CONCLUSION: The geographic variations in NHL rates may partially reflect differences in registration practices, disease classification, diagnostic practice, and death certification quality. There is a need for high-quality data and improvements in the accuracy of NHL histological diagnosis. Given the expected increase in NHL, careful monitoring of rates remains a priority to guide cancer control programs.