Relationships Between Patient Race and Residential Race Context With Missed Human Immunodeficiency Virus Care Visits in the United States, 2010-2015.

BACKGROUND: Racial inequities exist in retention in human immunodeficiency virus (HIV) care and multilevel analyses are needed to contextualize and address these differences. Leveraging data from a multisite clinical cohort of people with HIV (PWH), we assessed the relationships between patient race and residential characteristics with missed HIV care visits. METHODS: Medical record and patient-reported outcome (PRO; including mental health and substance-use measures) data were drawn from 7 participating Center for AIDS Research Network of Integrated Clinical Systems (CNICS) sites including N = 20 807 PWH from January 2010 through December 2015. Generalized estimating equations were used to account for nesting within individuals and within census tracts in multivariable models assessing the relationship between race and missed HIV care visits, controlling for individual demographic and health characteristics and census tract characteristics. RESULTS: Black PWH resided in more disadvantaged census tracts, on average. Black PWH residing in census tracts with higher proportion of Black residents were more likely to miss an HIV care visit. Non-Black PWH were less likely to miss a visit regardless of where they lived. These relationships were attenuated when PRO data were included. CONCLUSIONS: Residential racial segregation and disadvantage may create inequities between Black PWH and non-Black PWH in retention in HIV care. Multilevel approaches are needed to retain PWH in HIV care, accounting for community, healthcare setting, and individual needs and resources.

Supporting the implementation of new healthcare technologies by investigating generalisability of pilot studies using area-level statistics.

BACKGROUND: Implementation of new technologies into national health care systems requires careful capacity planning. This is sometimes informed by data from pilot studies that implement the technology on a small scale in selected areas. A critical consideration when using implementation pilot studies for capacity planning in the wider system is generalisability. We studied the feasibility of using publicly available national statistics to determine the degree to which results from a pilot might generalise for non-pilot areas, using the English human papillomavirus (HPV) cervical screening pilot as an exemplar. METHODS: From a publicly available source on population indicators in England ("Public Health Profiles"), we selected seven area-level indicators associated with cervical cancer incidence, to produce a framework for post-hoc pilot generalisability analysis. We supplemented these data by those from publicly available English Office for National Statistics modules. We compared pilot to non-pilot areas, and pilot regimens (pilot areas using the previous standard of care (cytology) vs. the new screening test (HPV)). For typical process indicators that inform real-world capacity planning in cancer screening, we used standardisation to re-weight the values directly observed in the pilot, to better reflect the wider population. A non-parametric quantile bootstrap was used to calculate 95% confidence intervals (CI) for differences in area-weighted means for indicators. RESULTS: The range of area-level statistics in pilot areas covered most of the spectrum observed in the wider population. Pilot areas were on average more deprived than non-pilot areas (average index of multiple deprivation 24.8 vs. 21.3; difference: 3.4, 95% CI: 0.2-6.6). Participants in HPV pilot areas were less deprived than those in cytology pilot areas, matching area-level statistics. Differences in average values of the other six indicators were less pronounced. The observed screening process indicators showed minimal change after standardisation for deprivation. CONCLUSIONS: National statistical sources can be helpful in establishing the degree to which the types of areas outside pilot studies are represented, and the extent to which they match selected characteristics of the rest of the health care system ex-post. Our analysis lends support to extrapolation of process indicators from the HPV screening pilot across England.

Impact of changes to the interscreening interval and faecal immunochemical test threshold in the national bowel cancer screening programme in England: results from the FIT pilot study.

INTRODUCTION: The NHS Bowel Cancer Screening Programme (BCSP) faces endoscopy capacity challenges from the COVID-19 pandemic and plans to lower the screening starting age. This may necessitate modifying the interscreening interval or threshold. METHODS: We analysed data from the English Faecal Immunochemical Testing (FIT) pilot, comprising 27,238 individuals aged 59-75, screened for colorectal cancer (CRC) using FIT. We estimated screening sensitivity to CRC, adenomas, advanced adenomas (AA) and mean sojourn time of each pathology by faecal haemoglobin (f-Hb) thresholds, then predicted the detection of these abnormalities by interscreening interval and f-Hb threshold. RESULTS: Current 2-yearly screening with a f-Hb threshold of 120 µg/g was estimated to generate 16,092 colonoscopies, prevent 186 CRCs, detect 1142 CRCs, 7086 adenomas and 4259 AAs per 100,000 screened over 15 years. A higher threshold at 180 µg/g would reduce required colonoscopies to 11,500, prevent 131 CRCs, detect 1077 CRCs, 4961 adenomas and 3184 AAs. A longer interscreening interval of 3 years would reduce required colonoscopies to 10,283, prevent 126 and detect 909 CRCs, 4796 adenomas and 2986 AAs. CONCLUSION: Increasing the f-Hb threshold was estimated to be more efficient than increasing the interscreening interval regarding overall colonoscopies per screen-benefited cancer. Increasing the interval was more efficient regarding colonoscopies per cancer prevented.

Extension of cervical screening intervals with primary human papillomavirus testing: observational study of English screening pilot data.

OBJECTIVES: To provide updated evidence about the risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and cervical cancer after a negative human papillomavirus (HPV) test in primary cervical screening, by age group and test assay. DESIGN: Observational study. SETTING: Real world data from the English HPV screening pilot's first and second rounds (2013-16, follow-up to end of 2019). PARTICIPANTS: 1 341 584 women. INTERVENTIONS: Cervical screening with HPV testing or liquid based cytological testing (cytology or smear tests). Women screened with cytology were referred to colposcopy after high grade cytological abnormalities or after borderline or low grade abnormalities combined with a positive HPV triage test. Women screened with HPV testing who were positive were referred at baseline if their cytology triage test showed at least borderline abnormalities or after a retest (early recall) at 12 and 24 months if they had persistent abnormalities. MAIN OUTCOME MEASURES: Detection of CIN3+ and cervical cancer after a negative HPV test. RESULTS: For women younger than 50 years, second round detection of CIN3+ in this study was significantly lower after a negative HPV screen in the first round than after cytology testing (1.21/1000 v 4.52/1000 women screened, adjusted odds ratio 0.26, 95% confidence interval 0.23 to 0.30), as was the risk of interval cervical cancer (1.31/100 000 v 2.90/100 000 woman years, adjusted hazard ratio 0.44, 0.23 to 0.84). Risk of an incident CIN3+ detected at the second screening round in the pilot five years after a negative HPV test was even lower in women older than 50 years, than in three years in women younger than 50 years (0.57/1000 v 1.21/1000 women screened, adjusted odds ratio 0.46, 0.27 to 0.79). Women with negative HPV tests at early recall after a positive HPV screening test without cytological abnormalities had a higher detection rate of CIN3+ at the second routine recall than women who initially tested HPV negative (5.39/1000 v 1.21/1000 women screened, adjusted odds ratio 3.27, 95% confidence interval 2.21 to 4.84). Detection after a negative result on a clinically validated APTIMA mRNA HPV test was similar to that after clinically validated cobas and RealTime DNA tests (for CIN3+ at the second round 1.32/1000 v 1.14/1000 women screened, adjusted odds ratio 1.05, 0.73 to 1.50). CONCLUSIONS: These data support an extension of the screening intervals, regardless of the test assay used: to five years after a negative HPV test in women aged 25-49 years, and even longer for women aged 50 years and older. The screening interval for HPV positive women who have negative HPV tests at early recall should be kept at three years.

Cytology interpretation after a change to HPV testing in primary cervical screening: Observational study from the English pilot.

BACKGROUND: Overcalling of abnormalities has been a concern for using cytology triage after positive high-risk human papillomavirus (HPV) tests in cervical screening. METHODS: The authors studied the detection of cytological and histological abnormalities at age 24 to 64 years, using data from the English HPV pilot. The pilot compared routine implementation of primary cervical screening based on cytology (N = 931,539), where HPV test results were not available before cytology reporting, with that based on HPV testing (N = 403,269), where cytology was only required after positive HPV tests. RESULTS: Revealed HPV positivity was associated with a higher direct referral to colposcopy after any abnormality (adjusted odds ratio [ORadj ], 1.16; 95% confidence interval [CI], 1.14-1.18). Laboratories with higher direct referral referred fewer persistently HPV-positive women after early recall. The detection of high-grade cervical intraepithelial neoplasia (CIN2+) after direct referral increased with an ORadj of 1.17 (95% CI, 1.13-1.20) for informed versus uninformed cytology. Generally, the positive predictive value (PPV) of colposcopy for CIN2+ remained comparable under both conditions of interpreting cytology. In women 50 to 64 years old with high-grade dyskaryosis, however, the PPV increased from 71% to 83% after revealing HPV positivity (ORadj , 2.05; 95% CI, 1.43-2.93). CONCLUSIONS: Quality-controlled cervical screening programs can avoid inappropriate overgrading of HPV-positive cytology.

The impact of catch-up bivalent human papillomavirus vaccination on cervical screening outcomes: an observational study from the English HPV primary screening pilot.

BACKGROUND: In England, bivalent vaccination (Cervarix) against high-risk human papillomavirus (HR-HPV) genotypes 16/18 was offered in a population-based catch-up campaign in 2008-2010 to girls aged 14-17 years. These women are now entering the national cervical screening programme. We determined the impact of catch-up bivalent vaccination on their screening outcomes. METHODS: We studied the overall and genotype-specific screening outcomes in 108,138 women aged 24-25 (offered vaccination) and 26-29 years (not offered vaccination) included in the English HPV screening pilot between 2013 and 2018. RESULTS: At 24-25 years, the detection of high-grade cervical intraepithelial neoplasia (CIN2+) associated with HPV16/18 decreased from 3 to 1% (p < 0.001), with estimated vaccine effectiveness of 87% (95% CI: 82-91%). The detection of any CIN2+ halved from 6 to 3% (p < 0.001), with an estimated vaccine effectiveness of 72% (95% CI: 66-77%). The positive predictive value of a colposcopy for CIN2+ decreased for both low-grade (p < 0.001) and high-grade (p = 0.02) abnormalities on triage cytology. The decreases in screen-detected abnormalities at age 26-29 were of a substantially smaller magnitude. CONCLUSIONS: These data confirm high effectiveness of bivalent HPV vaccination delivered through a population-based catch-up campaign in England. These findings add to the rationale for extending screening intervals for vaccinated cohorts.

Acceleration of cervical cancer diagnosis with human papillomavirus testing below age 30: Observational study.

Several international cervical screening guidelines advise against using high-risk human papillomavirus (HR-HPV) testing in women younger than 30. The rationale for this in young women, lies in the potential for additional detection of both low-grade and high-grade cervical intraepithelial neoplasia (CIN) leading to unnecessary treatments without reducing the burden of cervical cancer. We studied 56 544 women screened at 24 to 29 with HR-HPV testing and 116 858 screened with liquid-based cytology (LBC) in the English HPV screening pilot. They were compared to 528 460 women screened at the age of 30 to 49. We studied the detection of cervical cancer and CIN2/3 across two consecutive screening rounds 3 years apart. At 24 to 29, a positive HR-HPV test detected more cases of cervical cancer in the prevalence round than did a positive LBC test (1.36/1000 screened vs 0.82/1000, ORadj : 1.61, 95% CI: 1.18-2.19). In women with a negative HR-HPV test, cervical cancer was diagnosed before or at the incidence round in 0.07/1000. After a negative LBC test, cancer detection reached 0.47/1000 and 40% of these cases were diagnosed at FIGO stage IB+. HR-HPV testing increased the detection of CIN2/3 diagnoses in two consecutive rounds combined by 30% (71.9/1000 vs 55.2/1000). The patterns of detection of cervical cancer and CIN2/3 were almost identical at older ages. These data support using HR-HPV testing for screening of women younger than 30, which not only accelerates the diagnosis of cervical cancer but leads to a similar relative increase in CIN2/3 diagnosis to that found in women aged 30 to 49.

Age-specific outcomes from the first round of HPV screening in unvaccinated women: Observational study from the English cervical screening pilot.

OBJECTIVE: To report detailed age-specific outcomes from the first round of an English pilot studying the implementation of high-risk human papillomavirus (HR-HPV) testing in primary cervical screening. DESIGN: Observational study with screening in 2013-2016, followed by two early recalls and/or colposcopy until the end of 2019. SETTING: Six NHS laboratory sites. POPULATION: A total of 1 341 584 women undergoing screening with HR-HPV testing or liquid-based cytology (LBC). METHODS: Early recall tests and colposcopies were recommended, depending on the nature of the screening-detected abnormality. MAIN OUTCOME MEASURES: We reported standard screening process indicators, e.g. proportions with an abnormality, including high-grade cervical intraepithelial neoplasia (CIN2+) or cancer, and the positive predictive value (PPV) of colposcopy for CIN2+, by screening test and age group. RESULTS: Among unvaccinated women screened with HR-HPV testing at age 24-29 years, 26.9% had a positive test and 10.4% were directly referred to colposcopy following cytology triage, with a PPV for CIN2+ of 47%. At 50-64 years of age, these proportions were much lower: 5.3%, 1.2% and 27%, respectively. The proportions of women testing positive for HR-HPV without cytological abnormalities, whose early recall HR-HPV tests returned negative results, were similar across the age spans: 54% at 24-29 years and 55% at 50-64 years. Two-thirds of infections at any age were linked to non-16/18 genotypes. Among women with CIN2, CIN3 or cervical cancer, however, the proportion of non-16/18 infections increased with age. As expected, the detection of abnormalities was lower following screening with LBC. CONCLUSIONS: These data provide a reliable reference for future epidemiological studies, including those concerning the effectiveness of HPV vaccination. TWEETABLE ABSTRACT: Data from the English pilot study provide a comprehensive overview of abnormalities detected through HPV screening.

Impact of changing from a guaiac faecal occult blood test to a faecal immunochemical test in a national screening programme: Results from a pilot study within the national bowel cancer screening programme in England.

OBJECTIVE: Testing for occult blood in faeces is widely used in bowel cancer screening around the world. In many programmes, the faecal immunochemical test (FIT) is replacing the traditional guiaic faecal occult blood test (gFOBT). There have been a number of reports on the clinical impact of making this change; yet, no-one has considered the pre-analytical and analytical impact of moving from a gFOBT to a FIT bowel cancer screening programme. METHODS: We interrogated data obtained in a FIT pilot carried out in England in 2014 to assess the timeliness of specimen collection device return time and analysis for gFOBT and FIT, the impact of time to analysis on faecal haemoglobin (f-Hb) concentration, and any differences observed between analyses carried out at two different testing laboratories. RESULTS: FIT kits were returned on average 5.6 days sooner than gFOBT. The time to analysis for FIT leads to an overall rise in f-Hb concentration within the manufacturer's stated 14-day stability period. CONCLUSION: Both these factors are important considerations for laboratories when considering setting up a bowel cancer screening programme, especially if transitioning from gFOBT to FIT. Our data also support previous evidence of males having a higher f-Hb than females and demonstrate that after adjusting for sex, age and screening hub, neither index of multiple deprivation nor screening episode significantly affected f-Hb.

Attendance at early recall and colposcopy in routine cervical screening with human papillomavirus testing.

Attendance at early recall and colposcopy is crucial to attaining the benefits of primary high-risk human papillomavirus (HR-HPV)-based screening. Within the English HPV pilot, we analysed deprivation- and age-related patterns of attendance at colposcopy and 12- and 24-month early recall of HR-HPV positive women screened in 2013 to 2015 (N = 36 466). We fitted logistic regression models for adjusted odds ratios (OR). Despite high overall attendance, area deprivation had a small but significant impact at both early recalls, for example, attendance at 24 months was 86.3% and 83.0% in less vs more deprived areas, respectively (ORadj : 0.76; 95% CI: 0.67-0.87). Older women (≥30 years) were more likely to attend early recall than younger women (<30 years), for example, attendance at 24 months was 86.1% vs 82.3%, respectively (ORadj : 1.32, 95% CI: 1.16-1.51). Most women attended colposcopy following a baseline referral, with 96.9% attendance among more deprived and 97.8% among less deprived areas (ORadj : 0.70; 95% CI: 0.55-0.88). Differences in colposcopy attendance by deprivation level at 12 and 24 months were of approximately the same magnitude. In conclusion, attendance at early recall and colposcopy was reassuringly high. Although there were statistically significant differences by deprivation and age group, these were small in absolute terms.

Faecal immunochemical testing in bowel cancer screening: Estimating outcomes for different diagnostic policies.

OBJECTIVES: The National Health Service Bowel Cancer Screening Programme (NHS BCSP) in England has replaced guaiac faecal occult blood testing by faecal immunochemical testing (FIT). There is interest in fully exploiting FIT measures to improve bowel cancer (CRC) screening strategies. In this paper, we estimate the relationship of the quantitative haemoglobin concentration provided by FIT in faecal samples with underlying pathology. From this we estimate thresholds required for given levels of sensitivity to CRC and high-risk adenomas (HRA). METHODS: Data were collected from a pilot study of FIT in England in 2014, in which 27,238 participants completed a FIT. Those with a faecal haemoglobin concentration (f-Hb) of at least 20 µg/g were referred for further investigation, usually colonoscopy. Truncated regression models were used to explore the relationship between bowel pathology and FIT results. Regression results were applied to estimate sensitivity to different abnormalities for a number of thresholds. RESULTS: Participants with CRC and HRA had significantly higher f-Hb, and this remained unchanged after adjusting for age and sex. While a threshold of 20 µg/g was estimated to capture 82.2% of CRC and 64.0% of HRA, this would refer 7.8% of participants for colonoscopy. The current programme threshold used in England of 120 µg/g was estimated to identify 47.8% of CRC and 25.0% of HRA. CONCLUSIONS: Under the current diagnostic policy of dichotomising FIT results, a very low threshold would be required to achieve high sensitivity to CRC and HRA, which would place further strain on colonoscopy resources. The NHS BCSP in England might benefit from a diagnostic policy that makes greater use of the quantitative nature of FIT.

A state-wide population-based evaluation of cervical cancers arising during opportunistic screening in the United States.

OBJECTIVE: Despite widespread cervical screening, an estimated 13,800 women will be diagnosed with cervical cancer in the United States in 2020. To inform improvements, the screening histories of women diagnosed with cervical cancer in New Mexico were assessed. METHODS: Data were collected on all cervical screening, diagnostic tests and treatment procedures for all women diagnosed with cervical cancer aged 25-64 yrs. in New Mexico from 2006 to 2016. Women were categorized by their screening attendance in the 5-40 months (screening interval) and 1-4 months (peri-diagnostic interval) prior to cancer diagnosis. RESULTS: Of the 504 women diagnosed between May 2009-December 2016, 64% were not screened or had only inadequate screening tests in the 5-40 months prior to diagnosis, and 90 of 182 screened women (49%) had only negative screens in this period. Only 32% (N = 162) of cervical cancers were screen-detected. Women with adenocarcinomas were more likely to have had a recent negative screen (41/57 = 722%) than women with squamous cancers (50/112 = 45%). Both older women (aged 45-64 years) and women with more advanced cancers were less likely to have been screened, and if screened, were more likely to have a false-negative outcome. Only 9% of cancers were diagnosed in women who did not attend biopsy or treatment after positive tests requiring clinical management. Screening currently prevents 35% of cancers, whereas full screening coverage could prevent 61% of cervical cancers. CONCLUSION: Improved screening coverage has the largest potential for reducing cervical cancer incidence, though there is also a role for improved recall procedures and screening sensitivity.

Impact of screening on cervical cancer incidence: A population-based case-control study in the United States.

Cervical cancer is widely preventable through screening, but little is known about the duration of protection offered by a negative screen in North America. A case-control study was conducted with records from population-based registries in New Mexico. Cases were women diagnosed with cervical cancer in 2006-2016, obtained from the Tumor Registry. Five controls per case from the New Mexico HPV Pap Registry were matched to cases by sex, age and place of residence. Dates and results of all cervical screening and diagnostic tests since 2006 were identified from the pap registry. We estimated the odds ratio of nonlocalized (Stage II+) and localized (Stage I) cervical cancer associated with attending screening in the 3 years prior to case-diagnosis compared to women not screened in 5 years. Of 876 cases, 527 were aged 25-64 years with ≥3 years of potential screening data. Only 38% of cases and 61% of controls attended screening in a 3-year period. Women screened in the 3 years prior to diagnosis had 83% lower risk of nonlocalized cancer (odds ratio [OR] = 0.17, 95% CI: 0.12-0.24) and 48% lower odds of localized cancer (OR = 0.52, 95% CI: 0.38-0.72), compared to women not screened in the 5 years prior to diagnosis. Women remained at low risk of nonlocalized cancer for 3.5-5 years after a negative screen compared to women with no negative screens in the 5 years prior to diagnosis. Routine cervical screening is effective at preventing localized and nonlocalized cervical cancers; 3 yearly screening prevents 83% of nonlocalized cancers, with no additional benefit of more frequent screening. Increasing screening coverage remains essential to further reduce cervical cancer incidence.

16/18 genotyping in triage of persistent human papillomavirus infections with negative cytology in the English cervical screening pilot.

BACKGROUND: In the English pilot of primary cervical screening with high-risk human papillomavirus (HR-HPV), we exploited natural viral clearance over 24 months to minimise unnecessary referral of HR-HPV+ women with negative cytology. Three laboratories were permitted to use 16/18 genotyping to select women for referral at 12-month recall. We estimated the clinical impact of this early genotyping referral. METHODS: The observed numbers of women referred to colposcopy and with detected high-grade cervical intraepithelial neoplasia (CIN2+), and of women who did not attend early recall in the three laboratories were compared with those estimated to represent a situation without an early genotyping referral. The 95% confidence intervals (CI) for the differences between the protocols were calculated by using a parametric bootstrap. RESULTS: Amongst 127,238 screened women, 16,097 (13%) had HR-HPV infections. The genotyping protocol required 5.9% (95% CI: 4.4-7.7) additional colposcopies and led to a detection of 1.2% additional CIN2+ (95% CI: 0.6-2.0), while 2.3% (95% CI: 2.1-2.5) fewer HR-HPV+/cytology- women did not attend the early recall compared with the non-genotyping protocol. CONCLUSIONS: In a screening programme with high quality of triage cytology and high adherence to early recall,16/18 genotyping of persistent HPV infections does not substantially increase CIN2+ detection.

Primary cervical screening with high risk human papillomavirus testing: observational study.

OBJECTIVE: To provide the first report on the main outcomes from the prevalence and incidence rounds of a large pilot of routine primary high risk human papillomavirus (hrHPV) testing in England, compared with contemporaneous primary liquid based cytology screening. DESIGN: Observational study. SETTING: The English Cervical Screening Programme. PARTICIPANTS: 578 547 women undergoing cervical screening in primary care between May 2013 and December 2014, with follow-up until May 2017; 183 970 (32%) were screened with hrHPV testing. INTERVENTIONS: Routine cervical screening with hrHPV testing with liquid based cytology triage and two early recalls for women who were hrHPV positive and cytology negative, following the national screening age and interval recommendations. MAIN OUTCOME MEASURES: Frequency of referral for a colposcopy; adherence to early recall; and relative detection of cervical intraepithelial neoplasia grade 2 or worse from hrHPV testing compared with liquid based cytology in two consecutive screening rounds. RESULTS: Baseline hrHPV testing and early recall required approximately 80% more colposcopies, (adjusted odds ratio 1.77, 95% confidence interval 1.73 to 1.82), but detected substantially more cervical intraepithelial neoplasia than liquid based cytology (1.49 for cervical intraepithelial neoplasia grade 2 or worse, 1.43 to 1.55; 1.44 for cervical intraepithelial neoplasia grade 3 or worse, 1.36 to 1.51) and for cervical cancer (1.27, 0.99 to 1.63). Attendance at early recall and colposcopy referral were 80% and 95%, respectively. At the incidence screen, the 33 506 women screened with hrHPV testing had substantially less cervical intraepithelial neoplasia grade 3 or worse than the 77 017 women screened with liquid based cytology (0.14, 0.09 to 0.23). CONCLUSIONS: In England, routine primary hrHPV screening increased the detection of cervical intraepithelial neoplasia grade 3 or worse and cervical cancer by approximately 40% and 30%, respectively, compared with liquid based cytology. The very low incidence of cervical intraepithelial neoplasia grade 3 or worse after three years supports extending the screening interval.

Cancer risk in HIV patients with incomplete viral suppression after initiation of antiretroviral therapy.

BACKGROUND: Cancer causes significant morbidity and mortality among HIV patients in the US due to extended life expectancy with access to effective antiretroviral therapy. Low, detectable HIV RNA has been studied as a risk factor for adverse health outcomes, but its clinical impact on cancer risk remains unclear. The objective of this study was to determine whether HIV RNA <1,000 copies/mL six months after starting therapy was associated with 10-year first cancer risk. METHODS: We followed 7,515 HIV therapy initiators from a US-based multicenter clinical cohort from 1998 to 2014. We used nonparametric multiple imputation to account for viral loads that fell below assay detection limits, and categorized viral loads six months after therapy initiation into four groups: <20, 20-199, 200-999, and >999 copies/mL. We calculated estimates of the cumulative incidence of cancer diagnosis, accounting for death as a competing event. Inverse probability of exposure and censoring weights were used to control for confounding and differential loss to follow up, respectively. RESULTS: Crude 10-year first cancer risk in the study sample was 7.03% (95% CI: 6.08%, 7.98%), with the highest risk observed among patients with viral loads between 200 and 999 copies/mL six months after ART initiation (10.7%). After controlling for baseline confounders, 10-year first cancer risk was 6.90% (95% CI: 5.69%, 8.12%), and was similar across viral load categories. CONCLUSION: Overall risk of first cancer was not associated with incomplete viral suppression; however, cancer remains a significant threat to HIV patients after treatment initiation. As more HIV patients gain access to treatment in the current "treat all" era, occurrences of incomplete viral suppression will be observed more frequently in clinical practice, which supports continued study of the role of low-level HIV RNA on cancer development.

Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model.

BACKGROUND: The faecal immunochemical test (FIT) is replacing the guaiac faecal occult blood test in colorectal cancer screening. Increased uptake and FIT positivity will challenge colonoscopy services. We developed a risk prediction model combining routine screening data with FIT concentration to improve the accuracy of screening referrals. METHODS: Multivariate analysis used complete cases of those with a positive FIT (⩾20 µg g-1) and diagnostic outcome (n=1810; 549 cancers and advanced adenomas). Logistic regression was used to develop a risk prediction model using the FIT result and screening data: age, sex and previous screening history. The model was developed further using a feedforward neural network. Model performance was assessed by discrimination and calibration, and test accuracy was investigated using clinical sensitivity, specificity and receiver operating characteristic curves. RESULTS: Discrimination improved from 0.628 with just FIT to 0.659 with the risk-adjusted model (P=0.01). Calibration using the Hosmer-Lemeshow test was 0.90 for the risk-adjusted model. The sensitivity improved from 30.78% to 33.15% at similar specificity (FIT threshold of 160 µg g-1). The neural network further improved model performance and test accuracy. CONCLUSIONS: Combining routinely available risk predictors with the FIT improves the clinical sensitivity of the FIT with an increase in the diagnostic yield of high-risk adenomas.

Influence of Substance Use Disorders on 2-Year HIV Care Retention in the United States.

Substance use disorders (SUDs) are thought to predict care discontinuity, though magnitude and substance-specific variance of effects are unclear. This report of analytic work undertaken with a multi-regional American cohort of 9153 care enrollees addresses these gaps. Care retention was computed from 24-month post-linkage clinic visit documentation, with SUD cases identified from patient-report screening instruments. Two generalized estimating equations tested binary and hierarchial SUD predictors of retention, and potential effect modification by patient age-group, sex, and care site. Findings demonstrate: (1) detrimental SUD effect, equivalent to a nine percentage-point decrease in retention, with independent effects of age-group and care site; (2) substance-specific effect of marijuana UD associated with lower retention; and (3) age-modification of each effect on care discontinuity, with SUDs serving as a risk factor among 18-29 year-olds and protective factor among 60+ year-olds. Collective findings document patient attributes as influences that place particular subgroups at-risk to discontinue care.