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Assessing the risk of cancer among people living with HIV (PLHIV) in the current era of antiretroviral therapy (ART) is crucial, given their increased susceptibility to many types of cancer and prolonged survival due to ART exposure. Our study aims to compare the association between HIV infection and specific cancer sites in Rwanda. Population-based cancer registry data were used to identify cancer cases in both PLHIV and HIV-negative persons. A probabilistic record linkage approach between the HIV and cancer registries was used to supplement HIV status ascertainment in the cancer registry. Associations between HIV infection and different cancer types were evaluated using unconditional logistic regression models. We performed several sensitivity analyses to assess the robustness of our findings and to evaluate the potential impact of different assumptions on our results. From 2007 to 2018, the cancer registry recorded 17,679 cases, of which 7% were diagnosed among PLHIV. We found significant associations between HIV infection and Kaposi's Sarcoma (KS) (adjusted odds ratio [OR]: 29.1, 95% CI: 23.2-36.6), non-Hodgkin lymphoma (NHL) (1.6, 1.3-2.0), Hodgkin lymphoma (HL) (1.6, 1.1-2.4), cervical (2.3, 2.0-2.7), vulvar (4.0, 2.5-6.5), penile (3.0, 2.0-4.5), and eye cancers (2.2, 1.6-3.0). Men living with HIV had a higher risk of anal cancer (3.1, 1.0-9.5) than men without HIV, but women living with HIV did not have higher risk than women without HIV (1.0, 0.2-4.3). Our study found that in an era of expanded ART coverage in Rwanda, HIV is associated with a broad range of cancers, particularly those linked to viral infections., (© 2024 World Health Organization; licensed by UICC and The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

The relationship between body mass index (BMI) and melanoma and other skin cancers remains unclear. The objective of this study was to employ the Mendelian randomization (MR) approach to evaluate the effects of genetically predicted childhood adiposity on the risk of developing skin cancer later in life. Two-sample MR analyses were conducted using summary data from genome-wide association study (GWAS) meta-analyses of childhood BMI, melanoma, cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). We used the inverse-variance-weighted (IVW) methods to obtain a pooled estimate across all genetic variants for childhood BMI. We performed multiple sensitivity analyses to evaluate the potential influence of various assumptions on our findings. We found no evidence that genetically predicted childhood BMI was associated with risks of developing melanoma, cSCC, or BCC in adulthood (OR, 95% CI: melanoma: 1.02 (0.93-1.13), cSCC 0.94 (0.79-1.11), BCC 0.97 (0.84-1.12)). Our findings do not support the conclusions from observational studies that childhood BMI is associated with increased risks of melanoma, cSCC, or BCC in adulthood. Intervening on childhood adiposity will not reduce the risk of common skin cancers later in life., (© 2024. The Author(s).)

Observational studies have suggested that smoking may increase the risk of cutaneous squamous cell carcinoma (cSCC) while decreasing the risks of basal cell carcinoma (BCC), and melanoma. However, it remains possible that confounding by other factors may explain these associations. The aim of this investigation was to use Mendelian randomization (MR) to test whether smoking is associated with skin cancer, independently of other factors. Two-sample MR analyses were conducted to determine the causal effect of smoking measures on skin cancer risk using genome-wide association study (GWAS) summary statistics. We used the inverse-variance-weighted estimator to derive separate risk estimates across genetic instruments for all smoking measures. A genetic predisposition to smoking initiation was associated with lower risks of all skin cancer types, although none of the effect estimates reached statistical significance (OR 95% CI BCC 0.91, 0.82-1.01; cSCC 0.82, 0.66-1.01; melanoma 0.91, 0.82-1.01). Results for other measures were similar to smoking initiation with the exception of smoking intensity which was associated with a significantly reduced risk of melanoma (OR 0.67, 95% CI 0.51-0.89). Our findings support the findings of observational studies linking smoking to lower risks of melanoma and BCC. However, we found no evidence that smoking is associated with an elevated risk of cSCC; indeed, our results are most consistent with a decreased risk, similar to BCC and melanoma., (© 2023. Springer Nature Limited.)

Male-pattern baldness (MPB) is related to dysregulation of androgens such as testosterone. A previously observed relationship between MPB and skin cancer may be due to greater exposure to ultraviolet radiation or indicate a role for androgenic pathways in the pathogenesis of skin cancers. We dissected this relationship via Mendelian randomization (MR) analyses, using genetic data from recent male-only meta-analyses of cutaneous melanoma (12,232 cases; 20,566 controls) and keratinocyte cancers (KCs) (up to 17,512 cases; >100,000 controls), followed by stratified MR analysis by body-sites. We found strong associations between MPB and the risk of KC, but not with androgens, and multivariable models revealed that this relationship was heavily confounded by MPB single nucleotide polymorphisms involved in pigmentation pathways. Site-stratified MR analyses revealed strong associations between MPB with head and neck squamous cell carcinoma and melanoma, suggesting that sun exposure on the scalp, rather than androgens, is the main driver. Men with less hair covering likely explains, at least in part, the higher incidence of melanoma in men residing in countries with high ambient UV., (© 2023. Springer Nature Limited.)

Background: Skin screening is associated with higher melanoma detection rates, a potential indicator of overdiagnosis, but it remains possible that this effect is due to confounding by genetic risk., Objectives: To compare melanoma incidence among screened vs. unscreened participants within tertiles of genetic risk., Methods: We investigated melanoma incidence in the QSkin Study, a prospective cohort study which for this analysis comprised 15,283 participants aged 40-69 years with genotype data and no prior history of melanoma. We calculated a polygenic score (PGS) for melanoma. We first calculated age-standardised rate (ASR) of melanoma within PGS tertiles, and then measured the association between skin examination and melanoma detection by calculating the hazard ratio (HR) and 95% confidence interval (95% CI), overall and within PGS tertiles., Results: Melanoma incidence increased with PGS (ASR/100000/yr) tertile 1: 442; tertile 2: 519; tertile 3: 871). We found that the hazard ratios for all melanomas (i.e. in situ and invasive) associated with skin examination differed slightly across PGS tertiles (age- and sex-adjusted tertile 1 HR 1.88, 95% CI 1.26-2.81; tertile 2 HR 1.70, 95% CI 1.20-2.41; tertile 3 HR 1.96, 95% CI 1.43-2.70; fully adjusted tertile 1 HR 1.14, 95% CI 0.74-1.75; tertile 2 HR 1.21, 95% CI 0.82-1.78; tertile 3 HR 1.41, 95% CI 1.00-1.98) but these differences were not statistically significant. Hazard ratios for in situ melanoma associated with skin examination were similar across PGS tertiles. For invasive melanomas, the point estimates appeared highest in PGS tertile 3 in both minimally adjusted (age, sex) and fully adjusted models, however these apparent differences were also not statistically significant., Conclusions: Genetic risk predicts subsequent melanoma incidence, and is weakly associated with screening behaviour, but does not explain the higher rate of melanoma detection between screened and unscreened people., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To determine the proportions of newly diagnosed melanomas treated by different medical specialist types, to describe the types of excisions performed, and to investigate factors associated with treating practitioner specialty and excision type., Design, Setting: Prospective cohort study; analysis of linked data: baseline surveys, hospital, pathology, Queensland Cancer Register, and Medical Benefits Schedule databases., Participants: Random sample of 43 764 Queensland residents aged 40-69 years recruited during 2011, with initial diagnoses of in situ or invasive melanoma diagnosed to 31 December 2019., Main Outcome Measures: Treating practitioner type and treatment modality for first incident melanoma; second and subsequent treatment events for the primary melanoma., Results: During a median follow-up of 8.4 years (interquartile range, 8.3-8.8 years), 1683 eligible participants (720 women, 963 men) developed at least one primary melanoma (in situ melanoma, 1125; invasive melanoma, 558), 1296 of which (77.1%) were initially managed in primary care; 248 were diagnosed by dermatologists (14.8%), 83 by plastic surgeons (4.9%), 43 by general surgeons (2.6%), and ten by other specialists (0.6%). The most frequent initial procedures leading to histologically confirmed melanoma diagnosis were first excision (854, 50.7%), shave biopsy (549, 32.6%), and punch biopsy (178, 10.6%); 1339 melanomas (79.6%) required two procedures, 187 (11.1%) three. Larger proportions of melanomas diagnosed by dermatologists (87%) or plastic surgeons (71%) were in people living in urban areas than of those diagnosed in primary care (63%); larger proportions of melanomas diagnosed by dermatologists or plastic surgeons than of those diagnosed in primary care were in people with university degrees (45%, 42% v 23%) or upper quartile clinical risk scores (63%, 59% v 47%)., Conclusions: Most incident melanomas in Queensland are diagnosed in primary care, and nearly half are initially managed by partial excision (shave or punch biopsy). Second or third, wider excisions are undertaken in about 90% of cases., (© 2023 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Importance: An increasing number of people develop more than 1 primary melanoma, yet to date, no population-based prospective cohort studies have reported on risk factors for developing first vs second primary melanomas., Objective: To compare the clinical characteristics of first and second melanomas and then to estimate the relative risks of developing 1 vs multiple melanomas associated with demographic, phenotypic, sun exposure, and genetic factors., Design, Setting, and Participants: This population-based prospective cohort study included men and women aged 40 to 69 years recruited in 2011 and followed up until December 2018 in Queensland, Australia. Data analysis was performed from February to July 2022., Exposures: Self-reported information about demographic, phenotypic, and sun exposure measures captured using a survey completed at baseline, and polygenic risk score for melanoma., Main Outcomes and Measures: Incident first or second primary melanoma diagnosis, and histologic and clinical characteristics thereof. The Wei-Lin-Weissfeld model for recurrent events was used to estimate the association of each factor with the risks of first and second primary melanoma., Results: A total of 38 845 patients (mean [SD] age at baseline, 56.1 [8.2] years; 17 775 men and 21 070 women) were included in the study. During a median follow-up period of 7.4 years, 1212 (3.1%) participants had a single primary melanoma diagnosis, and 245 (0.6%) had a second primary melanoma diagnosis. Second melanomas were more likely than first melanomas to be in situ; for invasive tumors, second melanomas were more likely to be thin (ie, ≤1 mm) than first melanomas. Having many moles at age 21 years (self-reported using visual scoring tool) was more strongly associated with second (hazard ratio [HR], 6.36; 95% CI, 3.77-10.75) than first primary melanoma (HR, 3.46; 95% CI, 2.72-4.40) (P value for difference between the HRs = .01). A high genetic predisposition (ie, polygenic risk score in tertile 3) was also more strongly associated with second (HR, 3.28; 95% CI, 2.06-5.23) than first melanoma (HR, 2.06; 95% CI, 1.71-2.49; P = .03). Second melanomas were more strongly associated with a history of multiple skin cancer excisions (HR, 2.63; 95% CI, 1.80-3.83) than first melanomas (HR, 1.86; 95% CI, 1.61-2.16; P = .05). For all other phenotypic characteristics and sun exposure measures, similarly elevated associations with first vs second melanomas were observed., Conclusions and Relevance: Findings of this cohort study suggest that within the general population, the presence of many nevi and having a high genetic predisposition to melanoma were associated with the highest risks of developing second primary melanomas.

Because little is known about cataract in pilots, we estimated prevalence by anonymously ascertaining all commercial airline pilots diagnosed with cataract 2011-2016 using the electronic Medical Records System of the Australian Civil Aviation Safety Authority. Of 14,163 Australian male commercial pilots licensed in 2011, 1286 aged ≥60 had biennial eye examinations showing a cataract prevalence of 11.6%. Among 12,877 pilots aged <60, based on compulsory eye examinations only when first licensed, prevalence was 0.5%. There was no significant difference by ambient ultraviolet (UV) radiation levels in state of residence though lowest prevalence was seen in the low-UV state of Victoria. Most cataract in pilots ≥60 years was bilateral and of mild severity, while cataract in pilots <60 were more likely to be unilateral and of greater severity.

Background: Cutaneous melanomas are common cancers in white-skinned populations, and early detection is promoted as a means of reducing morbidity and mortality. There is concern that increased skin screening is leading to overdiagnosis of indolent melanomas with low risk of lethality. The extent of melanoma overdiagnosis associated with screening is unknown., Objectives: To estimate possible overdiagnosis by comparing subsequent melanoma incidence and biopsy rates among people subjected to skin screening those who were not., Methods: We recruited 43 762 residents of Queensland, Australia, aged 40-69 years, with no prior history of melanoma, selected at random from a population register in 2010. At baseline, participants completed a comprehensive melanoma risk factor survey and were asked if their skin had been examined by a doctor in the 3 years prior to baseline. We calculated incidence and relative risk of histologically confirmed melanoma (invasive and in situ) in years 2-7 of follow-up, obtained through linkage to the cancer registry. In secondary analyses, we measured biopsy rates in years 2-6 of follow-up. We used propensity score analysis to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs)., Results: In total, 28 155 participants underwent skin screening prior to baseline. We observed 967 first-incident melanomas (381 invasive) during 197 191 person-years of follow-up. Those screened had higher rates of melanoma (aHR 1·29, 95% CI 1·02-1·63) and subsequent skin biopses (aHR 1·85, 95% CI 1·69-2·04) than unscreened participants. The higher risk associated with skin screening was evident for in situ melanoma (aHR 1·45, 95% CI 1·09-1·92) but not invasive melanoma (aHR 1·05, 95% CI 0·72-1·54). In secondary analyses, where screening was defined as having a skin biopsy in the first year after baseline, we observed significantly increased risks of melanoma (aHR 1·53, 95% CI 1·23-1·89) and subsequent biopsies (aHR 2·64, 95% CI 2·46-2·84) relative to those who did not have a biopsy., Conclusions: People who undergo skin screening subsequently experience higher rates of biopsies and melanoma (especially in situ melanoma), even after adjusting for all known risk factors, consistent with overdiagnosis. What is already known about this topic? Cutaneous melanomas are common cancers in white-skinned populations for which early detection is promoted as a means of reducing morbidity and mortality. There is concern that increased surveillance is leading to the overdiagnosis of indolent melanomas that are not destined to be lethal. The extent of melanoma overdiagnosis associated with surveillance is not known. What does this study add? People subjected to skin examinations by a doctor or who undergo skin biopsies subsequently have higher numbers of biopsies and higher rates of melanoma than people not subjected to either, even after adjusting for all known risk factors. These findings suggest that heightened surveillance leads to a proportion of melanomas being diagnosed that otherwise may not have come to clinical attention., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Numerous epidemiologic studies have reported positive associations between higher nevus counts and internal cancers. Whether this association represents a true relationship or is due to bias or confounding by factors associated with both nevus counts and cancer remains unclear. We used germline genetic variants for nevus count to test whether this phenotypic trait is a risk-marker for cancer. We calculated polygenic risk scores (PRS) for nevus counts using individual-level data in the UK Biobank (n = 394 306) and QSkin cohort (n = 17 427). The association between the nevus PRS and each cancer site was assessed using logistic regression adjusted for the effects of age, sex and the first five principal components. In both cohorts, those in the highest nevus PRS quartile had higher risks of melanoma than those in the lowest quartile (UK Biobank odds ratio [OR] 1.42, 95% confidence interval [CI]: 1.29-1.55; QSkin OR 1.58, 95% CI: 1.29-1.94). We also observed increases in risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) associated with higher nevus PRS quartiles (BCC UK Biobank OR 1.38, 95% CI: 1.33-1.44; QSkin OR 1.20, 95% CI: 1.05-1.38 and SCC UK Biobank OR 1.41, 95% CI: 1.28-1.55; QSkin OR 1.44, 95% CI: 1.19-1.77). We found no consistent evidence that nevus count PRS were associated with risks of developing internal cancers. We infer that associations between nevus counts and internal cancers reported in earlier observational studies arose because of unmeasured confounding or other biases., (© 2021 UICC.)

Background: Epidemiological studies have consistently documented an increased risk of developing primary non-cutaneous malignancies among people with a history of keratinocyte carcinoma (KC). However, the mechanisms underlying this association remain unclear. We conducted two separate analyses to test whether genetically predicted KC is related to the risk of developing cancers at other sites., Methods: In the first approach (one-sample), we calculated the polygenic risk scores (PRS) for KC using individual-level data in the UK Biobank (n = 394 306) and QSkin cohort (n = 16 896). The association between the KC PRS and each cancer site was assessed using logistic regression. In the secondary (two-sample) approach, we used genome-wide association study (GWAS) summary statistics identified from the most recent GWAS meta-analysis of KC and obtained GWAS data for each cancer site from the UK-Biobank participants only. We used inverse-variance-weighted methods to estimate risks across all genetic variants., Results: Using the one-sample approach, we found that the risks of cancer at other sites increased monotonically with KC PRS quartiles, with an odds ratio (OR) of 1.16, 95% confidence interval (CI): 1.13-1.19 for those in KC PRS quartile 4 compared with those in quartile 1. In the two-sample approach, the pooled risk of developing other cancers was statistically significantly elevated, with an OR of 1.05, 95% CI: 1.03-1.07 per doubling in the odds of KC. We observed similar trends of increasing cancer risk with increasing KC PRS in the QSkin cohort., Conclusion: Two different genetic approaches provide compelling evidence that an instrumental variable for KC constructed from genetic variants predicts the risk of cancers at other sites., (© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Keratoacanthomas are common keratinocyte skin tumours. However, there is little community-based data published on the clinical features of keratoacanthoma. The aim of this study was to describe the patient and tumour characteristics of keratoacanthomas, as well as their treatment patterns. Data were obtained from the QSkin Sun and Health study, a prospective cohort of 40,438 randomly sampled and consented participants aged 40-69 years in Queensland, Australia. In 2010, a baseline survey collected data, including demography, phenotype, ultraviolet radiation exposure, medical history and lifestyle. Histopathological reports of keratoacanthomas arising until 30 June 2014 were reviewed. In total, 584 participants developed 738 keratoacanthomas; 18% of participants developed multiple tumours. Common patient characteristics were male sex (58%), age ≥60 years (76%), fair skin (80%), and previous history of actinic keratoses/keratinocyte cancers (89%). Keratoacanthomas were commonly located on the legs/feet (48%), and rarely on the the head/neck (7%). Excision was the most frequently used surgical method (71%) Evidence of histopathological regression was reported in 67% of keratoacanthomas, suggesting a potential for spontan-eous resolution in a significant proportion of keratoacanthomas.

Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.

Importance: Keratoacanthoma (KA) is a common and generally benign keratinocyte skin tumor. Reports of the incidence rates of KA are scant. In addition, the risk factors for KA are not well understood, although associations with UV radiation exposure and older age have been described., Objective: To investigate the incidence rate of KA and the risk factors for developing KA., Design, Setting, and Participants: The study included data from 40 438 of 193 344 randomly selected residents of Queensland, Australia, who participated in the QSkin Sun and Health (QSkin) prospective population-based cohort study. All participants completed a baseline survey between 2010 and 2011 and were ages 40 to 69 years at baseline. Histopathologic reports of KA were prospectively collected until June 30, 2014, through data linkage with pathologic records. Cox proportional hazards models were used to identify risk factors associated with KA while controlling for potential confounding variables. Data were analyzed from January 2 to April 8, 2020., Exposures: Demographic characteristics, phenotypes, UV radiation exposure, medical history, and lifestyle., Results: Among 40 438 participants (mean [SD] age, 56 [8] years; 18 240 men [45.1%]), 596 individuals (mean [SD] age, 62 [6] years; 349 men [58.6%]) developed 776 KA tumors during a median follow-up period of 3.0 years (interquartile range, 2.8-3.3 years). The person-based age-standardized incidence rate for KA in the age-restricted cohort was 409 individuals per 100 000 person-years (based on the 2001 Australian population). Risk factors after adjustment for potential confounders were older age (age ≥60 years vs age <50 years; hazard ratio [HR], 6.38; 95% CI, 4.65-8.75), male sex (HR, 1.56; 95% CI, 1.33-1.84), fair skin (vs olive, dark, or black skin; HR, 3.42; 95% CI, 1.66-7.04), inability to tan (vs ability to tan deeply; HR, 1.69; 95% CI, 1.19-2.40), previous excisions of keratinocyte cancers (ever had an excision vs never had an excision; HR, 6.28; 95% CI, 5.03-7.83), current smoking (vs never smoking, HR, 2.02; 95% CI, 1.59-2.57), and high alcohol use (≥14 alcoholic drinks per week vs no alcoholic drinks per week; HR, 1.42; 95% CI, 1.09-1.86)., Conclusions and Relevance: This is, to date, the first large prospective population-based study to report the incidence rate and risk factors for KA. The high person-based incidence rate (409 individuals per 100 000 person-years) highlights the substantial burden of KA in Queensland, Australia. Furthermore, the study's findings suggest that older age (≥60 years), male sex, UV radiation-sensitive phenotypes, indications of high sun exposure (eg, previous keratinocyte cancer excisions), smoking, and high alcohol use are independent risk factors for the development of KA.

Background: Height and body mass index (BMI) have both been positively associated with melanoma risk, although findings for BMI have been less consistent than height. It remains unclear, however, whether these associations reflect causality or are due to residual confounding by environmental and lifestyle risk factors. We re-evaluated these associations using a two-sample Mendelian randomization (MR) approach., Methods: We identified single nucleotide polymorphisms (SNPs) for BMI and height from separate genome-wide association study (GWAS) meta-analyses. We obtained melanoma SNPs from the most recent melanoma GWAS meta-analysis comprising 12 874 cases and 23 203 controls. We used the inverse variance-weighted estimator to derive separate causal risk estimates across all SNP instruments for BMI and height., Results: Based on the combined estimate derived from 730 SNPs for BMI, we found no evidence of an association between genetically predicted BMI and melanoma [odds ratio (OR) per one standard deviation (1 SD) (4.6 kg/m2) increase in BMI 1.00, 95% confidence interval (CI): 0.91-1.11]. In contrast, we observed a positive association between genetically-predicted height (derived from a pooled estimate of 3290 SNPs) and melanoma risk [OR 1.08, 95% CI: 1.02-1.13, per 1 SD (9.27 cm) increase in height]. Sensitivity analyses using two alternative MR methods yielded similar results., Conclusions: These findings provide no evidence for a causal association between higher BMI and melanoma, but support the notion that height is causally associated with melanoma risk. Mechanisms through which height influences melanoma risk remain unclear, and it remains possible that the effect could be mediated through diverse pathways including growth factors and even socioeconomic status., (© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Purpose: Keratinocyte cancers are exceedingly common in high-risk populations, but accurate measures of incidence are seldom derived because the burden of manually reviewing pathology reports to extract relevant diagnostic information is excessive. Thus, we sought to develop supervised learning algorithms for classifying basal and squamous cell carcinomas and other diagnoses, as well as disease site, and incorporate these into a Web application capable of processing large numbers of pathology reports., Methods: Participants in the QSkin study were recruited in 2011 and comprised men and women age 40-69 years at baseline (N = 43,794) who were randomly selected from a population register in Queensland, Australia. Histologic data were manually extracted from free-text pathology reports for participants with histologically confirmed keratinocyte cancers for whom a pathology report was available (n = 25,786 reports). This provided a training data set for the development of algorithms capable of deriving diagnosis and site from free-text pathology reports. We calculated agreement statistics between algorithm-derived classifications and 3 independent validation data sets of manually abstracted pathology reports., Results: The agreement for classifications of basal cell carcinoma (κ = 0.97 and κ = 0.96) and squamous cell carcinoma (κ = 0.93 for both) was almost perfect in 2 validation data sets but was slightly lower for a third (κ = 0.82 and κ = 0.90, respectively). Agreement for total counts of specific diagnoses was also high (κ > 0.8). Similar levels of agreement between algorithm-derived and manually extracted data were observed for classifications of keratoacanthoma and intraepidermal carcinoma., Conclusion: Supervised learning methods were used to develop a Web application capable of accurately and rapidly classifying large numbers of pathology reports for keratinocyte cancers and related diagnoses. Such tools may provide the means to accurately measure subtype-specific skin cancer incidence.

Background/objective: To describe the clinical settings in which keratinocyte cancers are excised in Queensland and describe the types of practitioners who excise them; to examine costs; and to identify predictors of hospital admission., Methods: We used linked data for participants from the QSkin study (n = 43 794), including Medicare claims and Queensland hospital admissions relating to treatment episodes for incident keratinocyte cancers from July 2011 to June 2015. We used multinomial logistic regression to measure associations between demographic and clinical characteristics and treatment setting. The median costs of Medicare claims (AU$) were calculated., Results: During 4 years of follow-up, there were 18 479 skin cancer excision episodes among 8613 people. Most excisions took place in private clinical rooms (89.7%), the remainder in hospitals (7.9% private; 2.4% public). Compared with other anatomical sites, skin cancers on the nose, eyelid, ear, lip, finger or genitalia were more likely to be treated in hospitals than in private clinical rooms (public hospital OR 5.7; 95%CI 4.5-7.2; private hospital OR 8.3; 95%CI 7.3-9.4). Primary care practitioners excised 83% of keratinocyte cancers, followed by plastic surgeons (9%) and dermatologists (6%). The median Medicare benefit paid was $253 in private clinical rooms and $334 in private hospitals. Out-of-pocket payments by patients treated in private hospitals were fourfold higher than those in private clinical rooms ($351 vs $80)., Conclusions: Most keratinocyte cancers are excised in primary care, although more than 10% of excisions occur in hospital settings., (© 2019 The Australasian College of Dermatologists.)

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been postulated as chemopreventive agents for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but findings from observational studies have been inconsistent, and clinical trial data are scant., Objectives: To examine the association between aspirin and NSAID (nonaspirin) use and the risk of BCC and SCC in a large cohort specifically designed for skin cancer outcomes., Methods: We used data from the QSkin Study, a prospective cohort of 43 764 residents of Queensland, Australia (34 630 were included in this study and 23 581 were used in our primary analyses). We used Cox proportional hazards models to estimate the hazard ratios (HRs) between self-reported aspirin and NSAID use 1 year prior to study baseline and the first histologically confirmed BCC or SCC for high-risk (history of skin cancer excisions or more than five actinic lesions treated) and average-to-low-risk participants (no history of skin cancer excision and at most five actinic lesions treated)., Results: After a median of 3 years of follow-up, 3421 participants developed BCC and 1470 SCC (2288 BCC and 932 SCC with complete covariate information). Among the high-risk group (1826 BCC and 796 SCC), compared with never use, frequent (at least weekly) NSAID use was associated with reduced risk of BCC (HR 0·84, 95% confidence interval 0·71-0.99) but not SCC. Aspirin use was associated with reduced risk of SCC (HR 0·77, 95% confidence interval 0·64-0·93) only among infrequent (less than weekly) users and was not associated with BCC. We observed no association between NSAID or aspirin use and the risk of BCC or SCC among average-to-low-risk participants., Conclusions: While some weakly inverse associations were observed between prior use of aspirin or NSAIDs and skin cancer, the inconsistent patterns of associations do not provide convincing evidence that these medications reduce subsequent skin cancer risk. Further data on doses, duration and long-term follow-up may help us to comprehend the cumulative dose effect., (© 2019 British Association of Dermatologists.)

Objectives: Occupational exposure to cosmic and ultraviolet radiation may increase airline pilots' risk of cutaneous melanoma. Meta-analyses of available data show a higher than average incidence of melanoma in airline pilots, but the most recent systematic review revealed that few contemporary data are available. Moreover, all relevant studies have been conducted in Northern Hemisphere populations. We therefore aimed to examine if Australian commercial pilots have a raised incidence of melanoma compared with the general population., Methods: We examined all melanoma histologically diagnosed among Australian-licensed commercial pilots in the period 2011-2016 by manually reviewing de-identified data in the medical records system of the Australian Civil Aviation Safety Authority. We estimated age-specific incidence rates and compared these with corresponding population rates using standardised incidence ratios (SIRs) as measures of relative risk. Expected numbers were calculated by multiplying age- and calendar period-specific person-years (PYs) with corresponding rates from the entire Australian population; 95% CI were calculated assuming a Poisson distribution of the observed cases., Results: In this cohort of Australian-licensed commercial pilots observed for 91 370 PYs, 114 developed a melanoma (51 invasive, 63 in situ). More than 50% of melanomas occurred on the trunk, and the predominant subtype was superficial spreading melanoma. The SIR for invasive melanoma was 1.20 (95% CI 0.89 to 1.55) and for melanoma in situ, 1.39 (95% CI 1.08 to 1.78)., Conclusion: Australian-licensed commercial pilots have a modestly raised risk of in situ melanoma but no elevation of invasive melanoma compared with the general population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

To delineate causal pathways for melanoma, it is essential to derive unbiased estimates of risk. Extant knowledge derives largely from case-control studies with potential for bias. In a population-based prospective study (QSkin, n = 38,854), we assessed melanoma risks associated with pigmentation characteristics and other phenotypes, and we explored additive interactions. We fitted Cox proportional hazards models to adjust for other factors to estimate the independent effects of each characteristic on melanoma risk. During a mean follow-up of 3.5 years, 642 (1.5%) participants developed melanoma (253 invasive, 389 in situ). The characteristics most strongly associated with invasive melanoma were self-reported nevus density at age 21 years (many vs. no moles hazard ratio [95% confidence interval] = 4.91 [2.81-8.55]), inability to tan (no tan vs. deep tan, hazard ratio [95% confidence interval] = 3.39 [1.85-6.20]), and red hair color (vs. black, hazard ratio [95% confidence interval] = 3.11 [1.50-6.43]). Propensity to sunburn was not associated with melanoma after tanning inability was adjusted for. People with both high nevus density and a history of multiple keratinocyte cancers had significantly higher melanoma risks than those with only one of those traits. We infer that melanoma risk is more strongly related to nevus density and inability to tan than susceptibility to sunburn., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Risk stratification can improve the efficacy and cost-efficiency of screening programs for early detection of cancer. We sought to derive a risk stratification tool for melanoma that was suitable for the general population using only self-reported information., Methods: We used melanoma risk factor information collected at baseline from QSKIN, a prospective cohort study of Queensland adults age 40 to 69 years at recruitment (n = 41 954). We examined two separate outcomes: 1) invasive melanomas and 2) all melanomas (invasive + in situ) obtained through data linkage to the cancer registry. We used stepwise Cox proportional hazards modeling to derive the risk models in a randomly selected two-thirds sample of the data set and assessed model performance in the remaining one-third validation sample., Results: After a median follow-up of 3.4 years, 655 (1.6%) participants developed melanoma (257 invasive, 398 in situ). The prediction model for invasive melanoma included seven terms. At baseline, the strongest predictors of invasive melanoma were age, sex, tanning ability, number of moles at age 21 years, and number of skin lesions treated destructively. The model for "all melanomas" (ie, invasive and in situ) included five additional terms. Discrimination in the validation data set was high for both models (C-index = 0.69, 95% confidence interval [CI] = 0.62 to 0.76, and C-index = 0.72, 95% CI = 0.69 to 0.75, respectively), and calibration was acceptable., Conclusions: Such a tool could be used to target surveillance activities to those at highest predicted risk of developing melanoma over a median duration of 3.4 years.

Introduction: The optimal method(s) for screening HIV-infected women, especially for those living in sub-Saharan Africa, for cervical precancer and early cancer has yet to be established., Methods and Analysis: A convenience sample of >5000 Rwandan women, ages 30-54 years and living with HIV infection, is being consented and enroled into a cross-sectional study of cervical cancer screening strategies. Participants are completing an administered short risk factor questionnaire and being screened for high-risk human papillomavirus (hrHPV) using the Xpert HPV assay (Cepheid, Sunnyvale, California, USA), unaided visual inspection after acetic acid (VIA) and aided VIA using the Enhanced Visual Assessment (EVA) system (Mobile ODT, Tel Aviv, Israel). Women positive for hrHPV and/or by unaided VIA undergo colposcopy, which includes the collection of two cervical specimens prior to undergoing a four-quadrant microbiopsy protocol. The colposcopy-collected specimens are being tested by dual immunocytochemical staining for p16 INK4a and Ki-67 (CINtec PLUS Cytology, Ventana, Tucson, Arizona, USA) and for E6 or E7 oncoprotein for 8 hrHPV genotypes (HPV16, 18, 31, 33, 35, 45, 52 and 58) using the next-generation AV Avantage hrHPV E6/E7 test (Arbor Vita Corporation, Freemont, California, USA). Women with a local pathology diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) or pathology review diagnosis of CIN grade three or more severe (CIN3+) will receive treatment. Clinical performance and cost-effectiveness (eg, sensitivity, specificity and predictive values) of different screening strategies and algorithms will be evaluated., Ethics and Dissemination: The protocol was approved by local and institutional review boards for human subjects research. At the completion of the study, results will be disseminated to the scientific community through peer-reviewed publication and to the Rwandan stakeholders through an external advisory panel., Competing Interests: Competing interests: This research study has received HPV tests for reduced or no cost from Cepheid, Arbor Vita Corporation, and Roche., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Previous studies suggest that smokers have lower risks of cutaneous melanoma than nonsmokers, but data from population-based prospective studies are scarce. We investigated associations between smoking and melanoma in a cohort study purpose-designed to investigate skin cancer outcomes. Methods: Participants with no prior history of melanoma ( n = 38,697) completed a risk factor survey at baseline (2011). Patients were followed through linkage to the cancer registry. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between smoking (including intensity, duration, time since quitting) and melanoma using multivariate Cox proportional hazards regression, accounting for death as a competing event. Results: During a mean follow-up of 3.5 years, invasive melanomas developed in 247 participants. Compared with never smokers, former smokers (but not current smokers) had lower risks of invasive melanoma (HR 0.76; 95% CI, 0.57-1.01). Among former smokers, risks were lower with greater quantity of cigarettes smoked (HR 0.75; 95% CI, 0.56-0.98 per 10 cigarettes/day). No association was observed with duration of smoking while longer time since quitting was associated with a relative risk of melanoma that was not significantly different from the null (HR 1.18; 95% CI, 0.91-1.51, for every 10 years since quitting). Conclusions: We observed complex associations between smoking and melanoma, with some suggestion that former smokers had lower risks than never or current smokers. The apparent inverse association among former smokers may be due to residual confounding, although surveillance bias or biological effects cannot be excluded entirely. Impact: Smoking does not increase the risk of cutaneous melanoma. Cancer Epidemiol Biomarkers Prev; 27(8); 874-81. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Sunlight is the principal environmental risk factor for keratinocyte cancers, but other carcinogens have also been implicated, including tobacco smoke. Findings have been conflicting, however. We investigated associations between cigarette smoking and incidence of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in QSkin, a prospective study of skin cancer (N = 43,794). Smoking history was self-reported at baseline; newly diagnosed BCCs and SCCs were ascertained through data linkage and verified by histopathology reports. We restricted analyses to white participants who at baseline reported no past history of skin cancer excisions and no more than five destructively treated actinic skin lesions. We fitted Cox proportional hazards models, adjusted for known confounders. Compared with never smokers, current smokers had significantly lower risks of BCC (hazard ratio = 0.6; 95% confidence interval = 0.4-0.9) but significantly higher risks of SCC (hazard ratio = 2.3; 95% confidence interval = 1.5-3.6). Former smokers had similar risks for BCC and SCC as never smokers. Among smokers, we observed no dose-response trends with duration of smoking, intensity, or time since quitting. On further analysis, current smokers had fewer skin examinations and procedures than never smokers, suggesting greater opportunities for detection among never smokers. Strengths include large sample size, prospective design, and virtually complete follow-up; however, histologic details were missing for a proportion of excised tumors. In conclusion, current smokers had a lower incidence of BCC (possibly because of detection bias) but higher rates of SCC., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: An important determinant of the effectiveness of HIV treatment programs is the capacity of sites to implement recommended services and identify systematic changes needed to ensure that invested resources translate into improved patient outcomes. We conducted a survey in 2014 of HIV care and treatment sites in the seven regions of the International epidemiologic Database to Evaluate AIDS (IeDEA) Consortium to evaluate facility characteristics, HIV prevention, care and treatment services provided, laboratory capacity, and trends in the comprehensiveness of care compared to data obtained in the 2009 baseline survey., Methods: Clinical staff from 262 treatment sites in 45 countries in IeDEA completed a site survey from September 2014 to January 2015, including Asia-Pacific with Australia ( n  = 50), Latin America and the Caribbean ( n  = 11), North America ( n  = 45), Central Africa ( n  = 17), East Africa ( n  = 36), Southern Africa ( n  = 87), and West Africa ( n  = 16). For the 55 sites with complete data from both the 2009 and 2014 survey, we evaluated change in comprehensiveness of care., Results: The majority of the 262 sites (61%) offered seven essential services (ART adherence, nutritional support, PMTCT, CD4+ cell count testing, tuberculosis screening, HIV prevention, and outreach). Sites that were publicly funded (64%), cared for adults and children (68%), low or middle Human Development Index (HDI) rank (68%, 68%), and received PEPFAR support (71%) were most often fully comprehensive. CD4+ cell count testing was universally available (98%) but only 62% of clinics offered it onsite. Approximately two-thirds (69%) of sites reported routine viral load testing (44-100%), with 39% having it onsite. Laboratory capacity to monitor antiretroviral-related toxicity and diagnose opportunistic infections varied widely by testing modality and region. In the subgroup of 55 sites with two surveys, comprehensiveness of services provided significantly increased across all regions from 2009 to 2014 (5.7 to 6.5, p  < 0.001)., Conclusion: The availability of viral load monitoring remains suboptimal and should be a focus for site capacity, particularly in East and Southern Africa, where the majority of those initiating on ART reside. However, the comprehensiveness of care provided increased over the past 5 years and was related to type of funding received (publicly funded and PEPFAR supported).

Setting: World Health Organization advocates for integration of HIV-tuberculosis (TB) services and recommends intensive case finding (ICF), isoniazid preventive therapy (IPT), and infection control ("Three I's") for TB prevention and control among persons living with HIV., Objective: To assess the implementation of the "Three I's" of TB-control at HIV treatment sites in lower income countries., Design: Survey conducted between March-July, 2012 at 47 sites in 26 countries: 6 (13%) Asia Pacific, 7 (15%), Caribbean, Central and South America, 5 (10%) Central Africa, 8 (17%) East Africa, 14 (30%) Southern Africa, and 7 (15%) West Africa., Results: ICF using symptom-based screening was performed at 38% of sites; 45% of sites used symptom-screening plus additional diagnostics. IPT at enrollment or ART initiation was implemented in only 17% of sites, with 9% of sites providing IPT to tuberculin-skin-test positive patients. Infection control measures varied: 62% of sites separated smear-positive patients, and healthcare workers used masks at 57% of sites. Only 12 (26%) sites integrated HIV-TB services. Integration was not associated with implementation of TB prevention measures except for IPT provision at enrollment (42% integrated vs. 9% non-integrated; p = 0.03)., Conclusions: Implementation of TB screening, IPT provision, and infection control measures was low and variable across regional HIV treatment sites, regardless of integration status.

Background: Survival after diagnosis is a fundamental concern in cancer epidemiology. In resource-rich settings, ambient clinical databases, municipal data and cancer registries make survival estimation in real-world populations relatively straightforward. In resource-poor settings, given the deficiencies in a variety of health-related data systems, it is less clear how well we can determine cancer survival from ambient data., Methods: We addressed this issue in sub-Saharan Africa for Kaposi's sarcoma (KS), a cancer for which incidence has exploded with the HIV epidemic but for which survival in the region may be changing with the recent advent of antiretroviral therapy (ART). From 33 primary care HIV Clinics in Kenya, Uganda, Malawi, Nigeria and Cameroon participating in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortia in 2009-2012, we identified 1328 adults with newly diagnosed KS. Patients were evaluated from KS diagnosis until death, transfer to another facility or database closure., Results: Nominally, 22% of patients were estimated to be dead by 2 years, but this estimate was clouded by 45% cumulative lost to follow-up with unknown vital status by 2 years. After adjustment for site and CD4 count, age <30 years and male sex were independently associated with becoming lost., Conclusions: In this community-based sample of patients diagnosed with KS in sub-Saharan Africa, almost half became lost to follow-up by 2 years. This precluded accurate estimation of survival. Until we either generally strengthen data systems or implement cancer-specific enhancements (e.g., tracking of the lost) in the region, insights from cancer epidemiology will be limited.

We determined the associations of HIV infection/CD4 count with markers of hepatocellular damage [elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and liver synthetic function (decreased albumin) in HIV-infected (HIV(+)) antiretroviral therapy (ART)-naive and uninfected (HIV(-)) Rwandan women. In 2005, 710 HIV(+) ART-naive and 226 HIV(-) women enrolled in the Rwanda Women's Interassociation Study and Assessment. Liver enzymes were measured with abnormality defined as either AST or ALT ≥1.25 times the upper limit of normal. Low serum albumin level was defined as <3.5 g/dl. Multivariable logistic regression analysis identified independent predictors of elevated AST/ALT and low serum albumin. HIV(-) women had the lowest prevalence (6.6%) of abnormal AST/ALT, with the highest prevalence (16.4%) in HIV(+) women with CD4 <200 cells/μl (p=0.01). The odds of having serum albumin <3.5 g/dl was 5.7-fold higher in HIV(+) than HIV(-) women (OR=5.68, 95% CI: 3.32-9.71). The risk of low albumin decreased from low to high CD4 count, with OR=2.62, 95% CI: 1.66, 4.14 and OR=1.57, 95% CI: 1.01, 2.43 in HIV(+) women with a CD4 count <200 and 200-350 cells/μl, respectively vs. HIV(+) with CD4 >350 (p<0.001 and p<0.05 for all comparisons). Our findings suggest that HIV-associated liver damage may occur in ART-naive patients. Although liver abnormality prevalences in this cohort of HIV-infected Rwandan women are less than reported in developed countries, caution is needed for risk assessment measures to monitor and screen HIV-infected patients pre- and post-ART initiation in African clinical settings to curtail potential risks associated with HIV infection.

Background: We longitudinally assessed predictors of insulin resistance (IR) change among HIV-uninfected and HIV-infected (ART-initiators and ART-non-initiators) Rwandan women., Methodology: HIV-infected (HIV+) and uninfected (HIV-) women provided demographic and clinical measures: age, body mass index (BMI) in Kg/(height in meters)2, Fat-Mass (FMI) and Fat-Free-Mass (FFMI) index, fasting serum glucose and insulin. Homeostasis Model Assessment (HOMA) was calculated to estimate IR change over time in log10 transformed HOMA measured at study enrollment or prior to ART initiation in 3 groups: HIV- (n = 194), HIV+ ART-non-initiators (n=95) and HIV+ ART-initiators (n=371). ANCOVA linear regression models of change in log10-HOMA were fit with all models included the first log10 HOMA as a predictor., Results: Mean±SD log10-HOMA was -0.18±0.39 at the 1st and -0.21±0.41 at the 2nd measure, with mean change of 0.03±0.44. In the final model (all women) BMI at 1st HOMA measure (0.014; 95% CI=0.006-0.021 per kg/m2; p<0.001) and change in BMI from 1st to 2nd measure (0.024; 95% CI=0.013-0.035 per kg/m2; p<0.001) predicted HOMA change. When restricted to subjects with FMI measures, FMI at 1st HOMA measure (0.020; 95% CI=0.010-0.030 per kg/m2; p<0.001) and change in FMI from 1st to 2nd measure (0.032; 95% CI=0.020-0.043 per kg/m2; p<0.0001) predicted change in HOMA. While ART use did not predict change in log10-HOMA, untreated HIV+ women had a significant decline in IR over time. Use or duration of AZT, d4T and EFV was not associated with HOMA change in HIV+ women., Conclusions: Baseline BMI and change in BMI, and in particular fat mass and change in fat mass predicted insulin resistance change over ~3 years in HIV-infected and uninfected Rwandan women. Exposure to specific ART (d4T, AZT, EFV) did not predict insulin resistance change in ART-treated HIV-infected Rwandan women.

Background: Initiation of antiretroviral therapy (ART) in the advanced stages of HIV infection remains a major challenge in sub-Saharan Africa. This study was conducted to better understand barriers and enablers to timely ART initiation in Rwanda where ART coverage is high and national ART eligibility guidelines first expanded in 2007-2008., Methods: Using data on 6326 patients (≥15 years) at five Rwandan clinics, we assessed trends and correlates of CD4 cell count at ART initiation and the proportion initiating ART with advanced HIV disease (CD4 <200 cells/μl or WHO stage IV)., Results: Out of 6326 patients, 4486 enrolling in HIV care initiated ART with median CD4 cell count of 211 cells/μl [interquartile range: 131-300]. Median CD4 cell counts at ART initiation increased from 183 cells/μl in 2007 to 293 cells/μl in 2011-2012, and the proportion with advanced HIV disease decreased from 66.2 to 29.4%. Factors associated with a higher odds of advanced HIV disease at ART initiation were male sex [adjusted odds ratios (AOR) = 1.7; 95% confidence interval (CI): 1.3-2.1] and older age (AOR46-55+vs.<25 = 2.3; 95% CI: 1.2-4.3). Among those initiating ART more than 1 year after enrollment in care, those who had a gap in care of 12 or more months prior to ART initiation had higher odds of advanced HIV disease (AOR = 5.2; 95% CI: 1.2-21.1)., Conclusion: Marked improvements in the median CD4 cell count at ART initiation and proportion initiating ART with advanced HIV disease were observed following the expansion of ART eligibility criteria in Rwanda. However, sex disparities in late treatment initiation persisted through 2011-2012, and appeared to be driven by later diagnosis and/or delayed linkage to care among men.

Background: New World Health Organization guidelines recommend high-risk human papillomavirus (hrHPV) screen-and-treat strategies for cervical cancer prevention. We describe risk of, and risk factors for, testing hrHPV positive in a pilot study of hrHPV screen-and-treat conducted in Rwanda., Methods: A total of 2,964 women, 1,289 HIV-infected (HIV [+]) and 1,675 HIV-uninfected (HIV [-]), aged 30-60 years and living in Rwanda were enrolled in 2010. Cervical specimens were collected and tested by careHPV, a DNA test for a pool of 14 hrHPV types. Prevalence with binomial 95% confidence intervals (95% CI) and determinants of testing hrHPV positive were calculated., Results: hrHPV prevalence was higher in HIV [+] (31.8%, 95% CI = 29.2-34.4%) than HIV [-] women (8.2%, 95% CI = 6.7-9.8%; P < 0.0001). Among HIV [+] women, there was a significant trend (ptrend <0.001) of higher hrHPV prevalence with lower CD4 cell count, with the highest hrHPV prevalence among those with <200 CD4 cell counts (45.5%, 95% CI = 34.8-56.4%). In multivariate analysis of HIV [+] women, testing hrHPV positive was positively associated CD4 count of <200 cells/μL, history of 3 or more sexual partners, and history of using hormonal contraception, and negatively associated with older age. In HIV [-] women, testing hrHPV positive was negatively associated only with older age groups of 45-49 and 50-60 years and surprisingly was not associated with lifetime number of sexual partners., Conclusion: hrHPV prevalence is high in HIV [+], especially in women with the lowest CD4 cell counts, which may have implications for utilizing hrHPV-based screening strategies such as screen-and-treat in these high-risk subgroups.

Setting: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons., Objective: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries., Design: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs., Results: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages., Conclusions: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.

Objectives: The purpose of these analyses was to determine the associations of HIV infection and related immune dysfunction with a glucose homeostasis in the population of antiretroviral-naïve HIV-infected and uninfected Rwandan women. We hypothesise that insulin resistance and its consequences in the developing countries may be further elevated with HIV infection itself regardless of antiretroviral therapy., Study Design: Cross-sectional analysis of a longitudinal cohort., Setting: Community-based women's associations., Participants: In 2005, 710 HIV-infected (HIV positive) antiretroviral naïve and 226 HIV-uninfected (HIV negative) women were enrolled in the Rwanda Women's Interassociation Study and Assessment (RWISA). Clinical and demographic parameters, CD4 count, fasting insulin and glucose levels, anthropometric measurements and Bioelectrical Impedance Analysis (BIA) were obtained. Linear models were fit to log-transformed Homeostasis Model Assessment (HOMA) with results exponentiated back to a multiplicative effect on the original scale., Primary Outcome Measures: The outcome, insulin resistance, was measured by the HOMA, calculated as fasting insulin (μU/mL)×fasting glucose (mmol/L)/22.5., Results: In adjusted models, HIV-positive women were less insulin resistant than HIV-negative; an HIV-positive woman tended to have 0.728 times as much (95% CI 0.681 to 0.861) HOMA than a comparable HIV-negative woman. Among the HIV-positive women, those with CD4 <200 cells/µL tended to have 0.741 times as much HOMA (95% CI 0.601 to 0.912) as did comparable women with CD4 >350 cells/µL. The older age was independently associated with a lower HOMA insulin resistance. After adjusting for body mass index, fat and fat-free mass were not independently associated with HOMA., Conclusions: This study found that HIV infection and more advanced HIV infection (CD4 counts <200 cells/µL) were associated with greater insulin sensitivity in antiretroviral naïve African women. These findings provide baseline information for the interpretation of future studies on the effect of antiretroviral therapy on metabolic insulin sensitivity derangements in African population.

Objectives: In resource-constrained settings, tuberculosis (TB) is a common opportunistic infection and cause of death in HIV-infected persons. TB may be present at the start of antiretroviral therapy (ART), but it is often under-diagnosed. We describe approaches to TB diagnosis and screening of TB in ART programs in low- and middle-income countries., Methods and Findings: We surveyed ART programs treating HIV-infected adults in sub-Saharan Africa, Asia and Latin America in 2012 using online questionnaires to collect program-level and patient-level data. Forty-seven sites from 26 countries participated. Patient-level data were collected on 987 adult TB patients from 40 sites (median age 34.7 years; 54% female). Sputum smear microscopy and chest radiograph were available in 47 (100%) sites, TB culture in 44 (94%), and Xpert MTB/RIF in 23 (49%). Xpert MTB/RIF was rarely available in Central Africa and South America. In sites with access to these diagnostics, microscopy was used in 745 (76%) patients diagnosed with TB, culture in 220 (24%), and chest X-ray in 688 (70%) patients. When free of charge culture was done in 27% of patients, compared to 21% when there was a fee (p = 0.033). Corresponding percentages for Xpert MTB/RIF were 26% and 15% of patients (p = 0.001). Screening practices for active disease before starting ART included symptom screening (46 sites, 98%), chest X-ray (38, 81%), sputum microscopy (37, 79%), culture (16, 34%), and Xpert MTB/RIF (5, 11%)., Conclusions: Mycobacterial culture was infrequently used despite its availability at most sites, while Xpert MTB/RIF was not generally available. Use of available diagnostics was higher when offered free of charge.

Objectives: Although haematological abnormalities are common manifestations of HIV infection, few studies on haematological parameters in HIV-infected persons have been undertaken in sub-Saharan Africa. The authors assessed factors associated with haematological parameters in HIV-infected antiretroviral-naïve and HIV-uninfected Rwandan women., Study Design: Cross-sectional analysis of a longitudinal cohort., Setting: Community-based women's associations., Participants: 710 HIV-infected (HIV+) antiretroviral-naïve and 226 HIV-uninfected (HIV-) women from the Rwanda Women's Interassociation Study Assessment. Haematological parameters categorised as (abnormal vs normal) were compared by HIV status and among HIV+ women by CD4 count category using proportions. Multivariate logistic regression models using forward selection were fit., Results: Prevalence of anaemia (haemoglobin (Hb) <12.0 g/dl) was higher in the HIV+ group (20.5% vs 6.3%; p<0.001), and increased with lower CD4 counts: ≥350 (7.6%), 200-349 (16%) and <200 cells/mm(3) (32.2%). Marked anaemia (Hb <10.0 g/dl) was found in 4.2% of HIV+ and none of the HIV- women (p<0.001), and was highest in HIV+ women with CD4 <200 cells/mm(3) (8.4%). The HIV+ were more likely than HIV- women (4.2 vs 0.5%, respectively, p=0.002) to have moderate neutropenia with white blood cells <2.0×10(3) cells/mm(3) and 8.4% of HIV+ women with CD4 <200 cells/mm(3) had moderate neutropenia. In multivariate logistic regression analysis, BMI (OR 0.87/kg/m(2), 95% CI 0.82 to 0.93; p<0.001), CD4 200-350 vs HIV- (OR 3.59, 95% CI 1.89 to 6.83; p<0.001) and CD4 <200 cells/mm(3) vs HIV- (OR 8.09, 95% CI 4.37 to 14.97; <0.001) had large independent associations with anaemia. There were large independent associations of CD4 <200 cells/mm(3) vs HIV- (OR 7.18, 95% CI 0.78 to 65.82; p=0.081) and co-trimoxazole and/or dapsone use (OR 5.69, 95% CI 0.63 to 51.45; p=0.122) with moderate neutropenia., Conclusions: Anaemia was more common than neutropenia or thrombocytopenia in the HIV-infected Rwandan women. Future comparisons of haematological parameters in HIV-infected patients before and after antiretroviral therapy initiation are warranted.

Introduction: The objectives of this study are to address if and how albumin can be used as an indication of malnutrition in HIV infected and uninfected Africans., Methods: In 2005, 710 HIV-infected and 226 HIV-uninfected women enrolled in a cohort study. Clinical/demographic parameters, CD4 count, albumin, liver transaminases; anthropometric measurements and Bioelectrical Impedance Analysis (BIA) were performed. Malnutrition outcomes were defined as body mass index (BMI), Fat-free mass index (FFMI) and Fat mass index (FMI). Separate linear predictive models including albumin were fit to these outcomes in HIV negative and HIV positive women by CD4 strata (CD4>350,200-350 and <200 cells/µl)., Results: In unadjusted models for each outcome in HIV-negative and HIV positive women with CD4>350 cells/µl, serum albumin was not significantly associated with BMI, FFMI or FMI. Albumin was significantly associated with all three outcomes (p<0.05) in HIV+ women with CD4 200-350 cells/µl, and highly significant in HIV+ women with CD4<200 cells/µl (P<0.001). In multivariable linear regression, albumin remained associated with FFMI in women with CD4 count<200 cells/µl (p<0.01) but not in HIV+ women with CD4>200., Discussion: While serum albumin is widely used to indicate nutritional status it did not consistently predict malnutrition outcomes in HIV- women or HIV+ women with higher CD4. This result suggests that albumin may measure end stage disease as well as malnutrition and should not be used as a proxy for nutritional status without further study of its association with validated measures.

Background: Body mass index (BMI) independently predicts mortality in studies of HIV infected patients initiating antiretroviral therapy (ART). We hypothesized that poorer nutritional status would be associated with smaller gains in CD4 count in Rwandan women initiating ART., Methods and Findings: The Rwandan Women's Interassociation Study and Assessment, enrolled 710 ART-naïve HIV-positive and 226 HIV-negative women in 2005 with follow-up every 6 months. The outcome assessed in this study was change in CD4 count at 6, 12, and 24 months after ART initiation. Nutritional status measures taken prior to ART initiation were BMI; height adjusted fat free mass (FFMI); height adjusted fat mass (FMI), and sum of skinfold measurements. 475 women initiated ART. Mean (within 6 months) pre-ART CD4 count was 216 cells/µL. Prior to ART initiation, the mean (±SD) BMI was 21.6 (±3.78) kg/m(2) (18.3% malnourished with BMI<18.5); and among women for whom the following were measured, mean FFMI was 17.10 (±1.76) kg/m(2); FMI 4.7 (±3.5) kg/m(2) and sum of skinfold measurements 4.9 (±2.7) cm. FFMI was significantly associated with a smaller change in CD4 count at 6 months in univariate analysis (-6.7 cells/uL per kg/m(2), p=0.03) only. In multivariate analysis after adjustment for covariates, no nutritional variable was associated with change in CD4 count at any follow up visit., Conclusion: In this cohort of African women initiating ART, no measure of malnutrition prior to ART was consistently associated with change in CD4 count at 6, 12, and 24 months of follow up, suggesting that poorer pre-treatment nutritional status does not prevent an excellent response to ART., (© 2011 Kiefer et al.)