Second Primary Cancers in People With HIV/AIDS: A National Data Linkage Study of Incidence and Risk Factors.

BACKGROUND: Evidence regarding the characteristics of second primary cancer (SPC) in people living with HIV (PLWHIV) is limited. SETTING: We performed a national population-based data linkage study to determine the incidence and risk factors of SPC in PLWHIV in Australia between 1982 and 2012. METHODS: We conducted a probabilistic data linkage study to compare the incidence of SPC over time, defined using HIV treatment eras, for SPCs related to oncogenic viral infection in comparison with non-infection-related SPCs. Risk factors considered included age at diagnosis of cancer, sex, HIV exposure modality, and CD4 + count. RESULTS: Of 29,383 individuals diagnosed with HIV, 3123 individuals who developed a first primary cancer were included in the analysis. Among them, 229 cases of SPC were identified across 27,398 person-years of follow-up. The most common SPCs were non-Hodgkin lymphomas (n = 71, 31%). The incidence of SPC overall did not change over time; however, there was an increase in individuals diagnosed with HIV in later eras ( P trend =0.001). The incidence of non-infection-related SPC increased over time and was associated with older age ( P trend = 0.005) and the acquisition of HIV in later eras ( P trend <0.001). Conversely, the incidence of infection-related SPC decreased ( P trend <0.001), but this was no longer significant after adjustment for age ( P trend = 0.14). CONCLUSIONS: The risk of SPC in PLWHIV in Australia remains high, with a temporal increase observed in non-infection-related cancer, likely due to aging of the population. Optimal screening and prevention strategies for SPC in PLWHIV are increasingly important.

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2021.

Abstract: The Australian Paediatric Surveillance Unit (APSU) has been conducting surveillance of rare communicable and non-communicable conditions in children since its inception in 1993. In this report, the results are described of surveillance of ten communicable diseases (and complications) for 2021, including the numbers of cases and incidence estimates; demographics; clinical features; and management and short-term outcomes. The included diseases are: acute flaccid paralysis (AFP); congenital cytomegalovirus (CMV); neonatal herpes simplex virus (HSV) infection; paediatric human immunodeficiency virus (HIV) infection; perinatal exposure to HIV; severe complications from influenza; juvenile-onset respiratory papillomatosis (JoRRP); congenital rubella syndrome; congenital varicella syndrome; and neonatal varicella infection. In 2021, cases of JoRRP were reported to the APSU for the first time since 2017, indicating potential gaps in HPV vaccination. AFP surveillance by APSU again contributed to Australia achieving a minimum target incidence of one AFP case per 100,000 children aged < 15 years. There were no cases of children with severe complications of influenza. No cases of varicella or congenital rubella were reported; however, at-risk populations, especially young migrant and refugee women from countries without universal vaccination programs, need to be screened and prioritised for vaccination prior to pregnancy. Cases of perinatal exposure to HIV continue to increase; however, the rate of mother-to-child-transmission remains at low levels due to the use of effective intervention strategies. Case numbers of congenital CMV and neonatal HSV remain steady in the absence of vaccines, prompting the need for greater awareness and education, with recent calls for target screening of at-risk infants for congenital CMV.

Clinical and Public Health Implications of Human T-Lymphotropic Virus Type 1 Infection.

Human T-lymphotropic virus type 1 (HTLV-1) is estimated to affect 5 to 10 million people globally and can cause severe and potentially fatal disease, including adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The burden of HTLV-1 infection appears to be geographically concentrated, with high prevalence in discrete regions and populations. While most high-income countries have introduced HTLV-1 screening of blood donations, few other public health measures have been implemented to prevent infection or its consequences. Recent advocacy from concerned researchers, clinicians, and community members has emphasized the potential for improved prevention and management of HTLV-1 infection. Despite all that has been learned in the 4 decades following the discovery of HTLV-1, gaps in knowledge across clinical and public health aspects persist, impeding optimal control and prevention, as well as the development of policies and guidelines. Awareness of HTLV-1 among health care providers, communities, and affected individuals remains limited, even in countries of endemicity. This review provides a comprehensive overview on HTLV-1 epidemiology and on clinical and public health and highlights key areas for further research and collaboration to advance the health of people with and at risk of HTLV-1 infection.

Time trends in cancer incidence in Australian people living with HIV between 1982 and 2012.

OBJECTIVES: The aim of the study was to describe time trends in cancer incidence in people living with HIV (PLHIV) in Australia between 1982 and 2012. METHODS: A population-based prospective study was conducted using data linkage between the national HIV and cancer registries. Invasive cancers identified in PLHIV were grouped into AIDS-defining cancers (ADCs), infection-related non-ADCs (NADCs), and non-infection-related NADCs. Crude and age-standardized incidence rates of cancers were calculated and compared over five time periods: 1982-1995, 1996-1999, 2000-2004, 2005-2008 and 2009-2012, roughly reflecting advances in HIV antiretroviral therapy. Standardized incidence ratios (SIRs) compared with the Australian general population were calculated for each time period. Generalized linear models were developed to assess time trends in crude and age-standardized incidences. RESULTS: For ADCs, the crude and age-standardized incidences of Kaposi sarcoma and non-Hodgkin lymphoma substantially declined over time (P-trend < 0.001 for all) but SIRs remained significantly elevated. For infection-related NADCs, there were significant increases in the crude incidences of anal, liver and head and neck cancers. Age-standardized incidences increased for anal cancer (P-trend = 0.002) and liver cancer (P-trend < 0.001). SIRs were significantly elevated for anal cancer, liver cancer and Hodgkin lymphoma. For non-infection-related NADCs, the crude incidence of colorectal, lung and prostate cancers increased over time, but age-standardized incidences remained stable. CONCLUSIONS: Continuous improvements and high coverage of antiretroviral therapy have reduced the incidence of ADCs in PLHIV in Australia. Clinical monitoring of anal and liver cancers in people living with HIV should be performed, given the increasing incidence of these cancers.

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2020.

ABSTRACT: For 27 years, national prospective data on selected rare childhood diseases have been collected monthly by the Australian Paediatric Surveillance Unit (APSU) from paediatricians and other clinical specialists who report cases in children aged up to 16 years. We report here the annual results of APSU surveillance in 2020 for ten rare communicable diseases and complications of communicable diseases, namely: acute flaccid paralysis (AFP); congenital cytomegalovirus (CMV) infection; neonatal herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV); paediatric HIV infection; severe complications of seasonal influenza; juvenile onset recurrent respiratory papillomatosis (JoRRP); congenital rubella syndrome; congenital varicella syndrome; and neonatal varicella infection. We describe the results for each disease in the context of the total period of study, including demographics, clinical characteristics, treatment and short-term outcomes. Despite challenges presented by the coronavirus disease 2019 (COVID-19) pandemic in 2020, more than 1,400 paediatricians reported regularly to the APSU and an overall monthly reporting rate of > 90% was achieved. The minimum AFP target of 1 case per 100,000 children aged less than 15 years was achieved and there were few cases of vaccine-preventable diseases (JoRRP, rubella, varicella). However, high cases of congenital CMV, neonatal HSV and perinatal exposure to HIV persist. There were no severe complications of seasonal influenza reported for the first time in 13 years. This is consistent with other surveillance data reporting a decline of influenza and other communicable diseases in 2020, and likely reflects the wider effects of public health measures to reduce transmission of SARS-CoV-2 in the Australian community.

Genital warts trends in Australian and overseas-born people in Australia: A cross-sectional trend analysis to measure progress towards control and elimination.

Background: Substantial declines in genital warts have been observed in countries with quadrivalent/nonavalent human papillomavirus (q/n HPV) vaccination programmes, with Australia showing the most pronounced and long-term reductions. No study has assessed progress towards elimination of genital warts in a nation-wide sample of patients, and migrants' contribution to population-level control of genital warts. We assessed Australia's progress towards genital warts elimination by examining trends in diagnoses in Australian- and overseas-born patients of sexual health clinics (SHCs) across Australia. Methods: A cross-sectional trend analysis of new genital warts diagnoses among first-time patients of 34 SHCs, between 2004 and 2018, was performed. Rate ratios (RR) were calculated using Poisson regression models, for comparing trends in proportions of new genital warts diagnoses in Australian- and overseas-born patients during the pre-vaccination era (2004-2007) and the vaccination era (2008-2018), and by 2018 relative to 2004-2007. Findings: A total of 439,957 new patients (Australian-born: 230,230; overseas-born: 209,727) were seen at SHCs, 6•4% were diagnosed with genital warts (Australian-born: 7•1%; overseas-born: 5•6%). By 2018, there had been a 64% reduction in the proportion of all SHC patients with a genital warts diagnosis relative to 2004-2007 (RR: 0•36, 95% CI: 0•35-0•38). The decline was more pronounced at 72% (RR: 0•28, 95% CI: 0 •27-0•30) among Australian-born patients, with the greatest reduction in women and men aged <21 years, at 98% (RR: 0•02, 95% CI: 0•01-0•03) and 92% (RR: 0•08, 95% CI: 0•06-0•11), respectively. By 2018, there was a 49% reduction in the proportion of overseas-born patients diagnosed with genital warts (RR: 0•51, 95% CI:0•48-0•54), and a 21% reduction in overseas-born patients from countries with no or bivalent HPV (bHPV) vaccination programme (RR: 0•79, 95% CI: 0•71-0•90). Interpretation: The substantial reductions in Australian-born people is a testament to the efficacy of quadrivalent (qHPV) and nonavalent (nHPV) vaccines and the high and wide-spread vaccination coverage in Australia. However, population-wide elimination of genital warts in Australia is dependent on other countries initiating or expanding their own HPV vaccination programmes. Funding: The Australian Government Department of Health and Seqirus Australia.

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2019.

The Australian Paediatric Surveillance Unit (APSU) has been prospectively collecting national data on rare childhood conditions since 1993, with monthly reporting of cases by paediatricians. In this report we describe annual results from studies for ten communicable diseases and complications of communicable diseases that were conducted using APSU surveillance in 2019 and place these in an historic context. Results are reported on acute flaccid paralysis, congenital cytomegalovirus infection, neonatal herpes simplex virus infection, perinatal exposure to HIV, paediatric HIV infection, severe complications of seasonal influenza, juvenile onset recurrent respiratory papillomatosis (JoRRP), congenital rubella syndrome, congenital varicella syndrome and neonatal varicella infection. APSU provides rich clinical data to complement data collected from other surveillance systems and to improve understanding and response to rare childhood infections.

Defining Elimination of Genital Warts-A Modified Delphi Study.

Background: Substantial declines in genital warts (GW) have been observed in countries with quadrivalent HPV vaccination programmes, with Australia showing the highest reductions due to early commencement and high vaccination coverage. There is a real potential to achieve GW elimination; however, no GW elimination definition exists. Taking Australia as a case study, we aimed to reach expert consensus on a proposed GW elimination definition using a modified Delphi process. Method: We used modelling and epidemiological data to estimate the expected number of new GW cases, from pre-vaccination (baseline) in 2006 to the year 2060 in Australian heterosexuals, men who have sex with men (MSM), and newly arrived international travellers and migrants. We used these data and the literature, to develop a questionnaire containing ten elimination-related items, each with 9-point Likert scales (1-strongly disagree; 9-strongly agree). The survey was completed by 18 experts who participated in a full day face-to-face modified Delphi study, in which individuals and then small groups discussed and scored each item. The process was repeated online for items where consensus (≥70% agreement) was not initially achieved. Median and coefficient of variation (COV) were used to describe the central tendency and variability of responses, respectively. Findings: There was a 95% participation rate in the face-to-face session, and 84% response rate in the final online round. The median item score ranged between 7.0 and 9.0 and the COV was ≤0.30 on all items. Consensus was reached that at ≥80% HPV vaccination coverage, GW will be eliminated as a public health problem in Australia by 2060. During this time period there will be a 95% reduction in population-level incidence compared with baseline, equivalent to <1 GW case per 10,000 population. The reductions will occur most rapidly in Australian heterosexuals, with 73%, 90% and 97% relative reductions by years 2021, 2030 and 2060, respectively. The proportion of new GW cases attributable to importation will increase from 3.6% in 2006 to ~49% in 2060. Interpretation: Our results indicate that the vaccination programme will minimise new GW cases in the Australian population, but importation of cases will continue. This is the first study to define GW elimination at a national level. The framework developed could be used to define GW elimination in other countries, with thresholds particularly valuable for vaccination programme impact evaluation. Funding: LK supported through an Australian Government Research Training Programme Scholarship; unconditional funding from Seqirus to support the Delphi Workshop.

Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that causes a lifelong infection. Several diseases, including an aggressive form of leukaemia, have been designated as associated with HTLV-1, whereby having HTLV-1 is a necessary condition for diagnosis. Beyond these diseases, there is uncertainty about other health effects of HTLV-1. We aimed to synthesise evidence from epidemiological studies on associations between health outcomes and HTLV-1. METHODS: For this systematic review and meta-analysis, we searched Embase, MEDLINE, MEDLINE In-Process, and Global Health for publications from their inception to July, 2018. We included cohort, case-control, and controlled cross-sectional studies that compared mortality or morbidity between people with and without HTLV-1. We excluded studies of psychiatric conditions, of symptoms or clinical findings only, of people who had undergone blood transfusion or organ transplant, and of population groups defined by a behavioural characteristic putting them at increased risk of co-infection with another virus. We extracted the risk estimates (relative risks [RRs] or odds ratios [ORs]) that reflected the greatest degree of control for potential confounders. We did a random-effects meta-analysis for groups of effect estimates where case ascertainment methods, age groups, and confounders were similar, presenting pooled estimates with 95% CIs and prediction intervals. FINDINGS: Of the 3318 identified studies, 39 met the inclusion criteria, examining 42 clinical conditions between them. The adjusted risk of death due to any cause was higher in people with HTLV-1 when compared with HTLV-1-negative counterparts (RR 1·57, 95% CI 1·37-1·80). From meta-analysis, HTLV-1 was associated with increased odds of seborrheic dermatitis (OR 3·95, 95% CI 1·99-7·81), Sjogren's syndrome (3·25, 1·85-5·70), and, inversely, with lower relative risk of gastric cancer (RR 0·45, 0·28-0·71). There were a further 14 diseases with significant associations or substantially elevated risk with HTLV-1 from single studies (eczema [children]; bronchiectasis, bronchitis and bronchiolitis [analysed together]; asthma [males]; fibromyalgia; rheumatoid arthritis; arthritis; tuberculosis; kidney and bladder infections; dermatophytosis; community acquired pneumonia; strongyloides hyperinfection syndrome; liver cancer; lymphoma other than adult T-cell leukaemia-lymphoma; and cervical cancer). INTERPRETATION: There is a broad range of diseases studied in association with HTLV-1. However, the elevated risk for death among people with HTLV-1 is not explained by available studies of morbidity. Many of the diseases shown to be associated with HTLV-1 are not fatal, and those that are (eg, leukaemia) occur too rarely to account for the observed mortality effect. There are substantial research gaps in relation to HTLV-1 and cardiovascular, cerebrovascular, and metabolic disease. The burden of disease associated with the virus might be broader than generally recognised. FUNDING: Commonwealth Department of Health, Australia.

Incidence and time trends of anal cancer among people living with HIV in Australia.

BACKGROUND: Anal cancer incidence increased markedly in people living with HIV (PLWHIV) after the introduction of HAART, but in a few setting settings, recent declines have been reported. We report the incidence and time trends of anal cancer in PLWHIV in Australia. STUDY DESIGN: A data linkage study between the National HIV Registries and the Australian Cancer Database. METHODS: Cases of anal squamous cell carcinoma (ASCC) in Australians aged 16 years and above diagnosed with HIV between 1982 and 2012 were identified. Standardized incidence ratios (SIRs) were calculated to compare incidence with that of the general population. Poisson regression models were developed to describe the time trends of ASCC over time and to compare ASCC risk within subgroups of PLWHIV. RESULTS: Among 28 696 individuals, a total of 129 cases of ASCC were identified. The crude incidence was 36.3 per 100 000 person-years and it increased sharply from 14.8 to 62.1 per 100 000 person-years between 1982-1995 and 2009-2012 (P trend <0.001). The SIR was 35.3 (95% confidence interval 29.5-42.0), and there was an inverse association between SIR and increasing age (P trend <0.001). In multivariate analyses, ASCC incidence was significantly higher in recent years (P trend <0.001), in those who acquired HIV through male homosexual contact (P = 0.002), and in those who had a history of AIDS (P < 0.001). CONCLUSION: PLWHIV in Australia are at markedly higher risk of anal cancer. Unlike in some industrialized countries with a mature HIV epidemic, the incidence of anal cancer is still increasing in this population in Australia.

Decline in prevalence of human papillomavirus infection following vaccination among Australian Indigenous women, a population at higher risk of cervical cancer: The VIP-I study.

BACKGROUND: Cervical cancer occurrence and mortality are strongly correlated with socioeconomic disadvantage, largely due to unequal access to screening and treatment. Universal human papillomavirus (HPV) vaccination provides the opportunity to greatly reduce this global health disparity. Australian Indigenous women have substantially higher rates of cervical cancer than non-Indigenous women, primarily due to under-screening. We investigated HPV infection rates in Indigenous women 7 years after implementation of the national HPV vaccination program. METHODS: We used a repeat cross-sectional design, with the baseline being provided by an HPV prevalence survey among Indigenous women attending clinics for cervical cytology screening, prior to the start of the vaccination program in 2007. We returned to clinics in four locations during 2014-15, and invited women aged 18-26 years attending for screening to provide a cervical specimen for HPV testing, as well as to complete a short questionnaire and consent to allow access of their records in the National HPV Vaccination Program Register. We used well-established laboratory methods to test specimens for specific HPV genotypes. RESULTS: A total of 142 women were recruited at participating sites and compared to 155 who had been recruited at the same locations in the 2007 pre-vaccine survey. The two groups were identical in regard to age, with the more recent group having a higher proportion of hormonal contraception users, and a lower proportion of smokers. The proportion found to have any HPV type fell from 58 to 36% with the decline being entirely due to reductions in vaccine types, which fell by 94% from 24 to 1.4%. CONCLUSION: Australia's national HPV vaccination program appears to be successfully protecting a very high proportion of Indigenous women against vaccine targeted HPV types, who have in the past been at elevated risk of cervical cancer.

Patient, staffing and health centre factors associated with annual testing for sexually transmissible infections in remote primary health centres.

BACKGROUND: In high-incidence Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) settings, annual re-testing is an important public health strategy. Using baseline laboratory data (2009-10) from a cluster randomised trial in 67 remote Aboriginal communities, the extent of re-testing was determined, along with the associated patient, staffing and health centre factors. METHODS: Annual testing was defined as re-testing in 9-15 months (guideline recommendation) and a broader time period of 5-15 months following an initial negative CT/NG test. Random effects logistic regression was used to determine factors associated with re-testing. RESULTS: Of 10559 individuals aged ≥16 years with an initial negative CT/NG test (median age=25 years), 20.3% had a re-test in 9-15 months (23.6% females vs 15.4% males, P<0.001) and 35.2% in 5-15 months (40.9% females vs 26.5% males, P<0.001). Factors independently associated with re-testing in 9-15 months in both males and females were: younger age (16-19, 20-24 years); and attending a centre that sees predominantly (>90%) Aboriginal people. Additional factors independently associated with re-testing for females were: being aged 25-29 years, attending a centre that used electronic medical records, and for males, attending a health centre that employed Aboriginal health workers and more male staff. CONCLUSIONS: Approximately 20% of people were re-tested within 9-15 months. Re-testing was more common in younger individuals. Findings highlight the importance of recall systems, Aboriginal health workers and male staff to facilitate annual re-testing. Further initiatives may be needed to increase re-testing.