Supplementary Table 1. Modifications to study protocol
Published protocol Modification and Justification
Search conference abstracts from last 5 years. Did not include because of limited reported information in abstracts.
Use of Newcastle-Ottawa scale and framework developed by Hayden and colleagues for study quality assessment.
Did not use Hayden framework because designed primarily for evaluation of quality of prognosis studies.
Use of Comprehensive Meta-Analysis and STATA version 13 for statistical analyses.
Used RevMan5 for analyses, as recommended by Cochrane.
Supplementary Table 21. Example of PICO parameters used to identify potentially relevant publications published up to 28 June 2016 in MedLine in a systematic review of colorectal cancer in those HIV+ compared to an uninfected population.
Database Search strategy Ovid MEDLINE® <1946 to present>
In-process & Other Non-Indexed Citations and Ovid
1 exp HIV/ or *HIV-1/ or *HIV-2 (88981) 2 exp hiv infections/ (245938)
3 (hiv or human immunodeficiency or acquired immunodeficiency syndrome or acquired immune deficiency syndrome or aids or hiv + or seropositivity).tx.(332621) 4 exp Opportunistic Infections/ (32202) 5 Opportunistic infections.mp. (36455) 6 exp Acquired Immunodeficiency Syndrome/ (75351)
7 Acquired Immun??deficiency Syndrome.mp. (87155)
8 or/1-7 (379239)
9 exp Colorectal Neoplasms/ (155711) 10 (colorectal adj5 (cancer$ or
neoplasm$)).ti,ab. (68097)
11 exp Neoplasms/ and colon/ (10457) 12 exp neoplasms/ and rectum/ (9460) 13 or/9-12 (176835)
14 8 and 13
15 predict:.mp. or scor:.tw. or observ:.mp.
[validated filter from McMaster University HIRU for clinical predictions] (3893472) 16 risk:.mp. or exp cohort studies/ or between group:.tw. [validated filter from McMaster University HIRU for etiology]
(2851578)
17 15 or 16 (5861020) 18 14 and 17 (722)
19 remove duplicates form 18 (659)
Supplementary Table 23. Customized checklist of title and abstract screening for study selection of potentially relevant publications in a systematic review of colorectal cancer in those HIV+
compared to an uninfected population.
Inclusion criteria
1) Study population: Does the study include HIV positive adults (≥18 years, men or women)? To be included, the publication must also include a comparison of people who are not HIV positive (e.g. general population).
2) Study design: Is the study one of the following design: cross-sectional, case-control, prospective or retrospective cohort, cross-over, case cohort, non-randomized, other observational design not listed?
3) Outcome measure(s): Does the study report one or more of the following outcomes or measures for colorectal or colon cancer (excluding cancer of the rectum)?:
- Primary outcomes – standardized incidence ratio (95% confidence intervals);
relative risk ratio, risk ratio, odd ratio, or hazard ratio; or number of HIV positive participants, including duration of follow-up and number of cases, compared to number in comparison population, including duration of follow-up and number of cases
- Secondary outcomes – risk factors for colorectal cancer among HIV positive
population; stage of diagnosis; site of diagnosis; treatment; mortality attributed to colorectal cancer (e.g. standardized mortality ration, hazard ratio
Supplementary Table 34. Data extracted from included publications identified in a systematic review of colorectal cancer in those HIV+ compared to an uninfected population.
Data Publication
details
Year of publication, language of publication, country in which study was conducted
Design Type of study, study temporality, population-based, type of center where study was conducted, duration of study, follow-up time
Study participants
Age, sex, number of persons with HIV, number of control subjects, description of persons with HIV (years diagnosed with HIV, HIV acquisition risk factors, CD4+ cell count and viral load at time of colorectal cancer diagnosis, percentage receiving combination antiretroviral therapy, combination antiretroviral therapy regimen), description of control population (healthy individuals, general population, other underlying medical condition), attrition and reason(s) for loss to follow-up, comorbid illness(es)
Outcome measures
Standardized incidence ratio (or odds/risk/rate ratio) of colorectal cancer, numbers of observed and expected cases in both those with HIV and control population, stage of diagnosis, site of cancer, screening/diagnostic modality (fecal occult blood test, colonoscopy, sigmoidoscopy, other), number of deaths (total and cancer-related), standardized mortality ratio, treatment(s) received, treatment outcome(s)
Supplementary Table 54. PRISMA Checklist for reporting a systematic review and meta-analysis of colorectal cancer in in those HIV+
compared to an uninfected population up to 28 June 2016.
Section/topic # Checklist item Reported on page #
TITLE
Title 1 Identify the report as a systematic review, meta-analysis, or both. 12 ABSTRACT
Structured summary 2 Provide a structured summary including, as applicable: background; objectives;
data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.
4-53
INTRODUCTION
Rationale 3 Describe the rationale for the review in the context of what is already known. 5-64-5 Objectives 4 Provide an explicit statement of questions being addressed with reference to
participants, interventions, comparisons, outcomes, and study design (PICOS).
65-6
METHODS Protocol and registration
5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.
65
Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.
6-7
Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.
65
Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.
33 (Supp. Table 1)Supplementary
Table 2 Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in
systematic review, and, if applicable, included in the meta-analysis).
6-7, 34 (Supp. Table 2)5-6
Data collection process
10 Describe method of data extraction from reports (e.g., piloted forms,
independently, in duplicate) and any processes for obtaining and confirming data from investigators.
7, 35 (Supplementary . Table 3)
Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.
35 6, Supplementary Table 3(Supp. Table 3) Risk of bias in
individual studies
12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.
87
Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means). 7-8 Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done,
including measures of consistency (e.g., I2) for each meta-analysis.
7-8
Risk of bias across studies
15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).
7-8
Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.
8
RESULTS
Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.
9,30 (Figure 1)Figure 1
Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.
8-9,9, Table 1 23-27 (Table 1)
Risk of bias within studies
19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).
9, 28-29 (Table 2)
Results of individual studies
20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and
9-11, Figures 2 and 3, Supplementary
confidence intervals, ideally with a forest plot. Figures 1 to 331-32 (Figures 2-3)
Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency.
9-11, Figures 2 and 3, Supplementary Figures 1 to 3319-11, 31-32 (Figures 2-3) Risk of bias across
studies
22 Present results of any assessment of risk of bias across studies (see Item 15). 9,101,
Supplementary Figure 4
Additional analysis 23 Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]).
10-11
DISCUSSION Summary of evidence
24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).
11-12
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review- level (e.g., incomplete retrieval of identified research, reporting bias).
11-1214-15
Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.
12-14
FUNDING
Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.
n/a2
Supplementary Table 56. Studies not included identified in a systematic review of colorectal cancer in those HIV+ compared to an uninfected population in observational studies up to 28 June 2016 but not included in meta-analysis due to overlapping populations.
Included Study Removed study Shiels et al. 201548 5 Simard et al. 201039 6
Shiels et al. 201044 1*
Marcus et al.
201550 47
Silverberg et al.
2011 4037
Chen et al. 201557 4 Chen et al. 201456 3
* Included in meta-analysis of studies reporting colon cancer
Supplementary Figure 1. Results from random effect meta-analysis of standardized incidence ratio and 95% confidence intervals of incident colon cancer among those HIV+ compared to an uninfected population.
Supplementary Figure 2. Results from random effect meta-analysis of standardized incidence ratio and 95% confidence intervals of incident colorectal cancer in women with HIV compared to HIV-negative women.
Supplementary Figure 3. Results from random effect meta-analysis of standardized incidence ratio and 95% confidence intervals of incident colorectal cancer in men with HIV compared to HIV-negative men.
Supplementary Figure 14. Funnel plot∆ of studies included in a meta-analysis of incidence colorectal and colon cancer (excluding cancer of the rectum) in those HIV+ compared to an uninfected population.
∆Statistical results of publication bias included Begg’s adjusted rank correlation test (p = 0.78) and Egger’s regression asymmetry (p = 0.28).
