Anal HPV Tests in Screening for Cell Changes in the Anus in Patients With HIV: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Anal HPV Tests in Screening for Cell Changes in the Anus in Patients With HIV (NCT01946139), a na na study. The primary outcome is Specificity of Each Other Methods of HSIL Detection for APTIMA Assay.

2. Clinical Question

3. Trial Design

This completed clinical trial evaluated anal screening methods in a single group. The registry record lists an enrollment of 276, a start date of 2013-12-04, primary completion on 2018-10-31, and status as completed. It identifies the study as screening HIV-infected women for anal cancer precursors. The listed conditions are anal cancer, HIV infection, and human papilloma virus infection.

The screening schedule included baseline and assessments at 6, 12, 18, and 24 months. The listed methods were anal cytology, HPV hybrid capture 2, HPV mRNA assays, and OncoHealth HPVE6/E7 oncoprotein. The study also lists laboratory biomarker analysis, questionnaire administration, and quality-of-life assessment. Acceptability of anal cancer screening is named as a secondary outcome.

The registry lists the phase as NA, allocation as NA, masking as none, and model as single group. These entries do not describe a randomized allocation or a blinded comparison. The record does not identify a separate control group, and the screening methods should not be interpreted as independently randomized treatment arms. Their evaluation within one study is not, by itself, evidence of a controlled comparison.

The registry lists five outcome measures and zero analyses. It does not report a statistical analysis plan, participant flow, analysis populations beyond the primary outcome description, or numerical results for the primary outcome. A separate sample-size justification is not reported in the registry record. Any planning illustration based on an observed effect is distinct from the study’s actual design and cannot establish that the trial was designed with that effect in mind.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants who were negative for HSIL on the high resolution anoscopy at baseline and who had APTIMA assay results

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Participants who were entered into the AMC084 study

6. Primary Endpoint

The registry lists the primary outcome as Specificity of Each Other Methods of HSIL Detection for APTIMA Assay, measured over at baseline.

The primary outcome is described as the specificity of other HSIL detection methods for the APTIMA assay. Its stated measure is the number of participants who tested negative for HSIL on APTIMA among those who were negative for HSIL on high resolution anoscopy at baseline and had APTIMA results. The timeframe is baseline.

In general, specificity concerns how often a test gives a negative result among people who do not have the condition according to a reference assessment. This endpoint uses high resolution anoscopy to define the relevant baseline group and records negative APTIMA results within that group. A count can describe how many participants had a negative result, but by itself it does not convey the proportion of the eligible group with a negative result. The registry description does not specify a denominator-based estimate or report the count.

Assessing test results against a reference assessment is one way to describe diagnostic classification. The endpoint title refers to other methods in relation to APTIMA, while the description specifically defines a count of negative APTIMA results among HRA-negative participants. That wording does not provide a complete comparative accuracy analysis for each listed method. The registry record does not report sensitivity, a specificity proportion, confidence intervals, or a statistical test for this primary outcome. Therefore, the measure’s intended population and direction are described, but its numerical result and precision are not reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the question an outcome is intended to answer, the population in which it is measured, and the way the result is summarized. In this study, the primary measure is defined at baseline among participants negative for HSIL on high resolution anoscopy and with APTIMA results. The measure is a count of those who tested negative for HSIL on APTIMA. The registry record gives no numerical count, subgroup denominator, or analysis result.

What does a count measure?

A count states how many observations meet a defined condition. It is not automatically a rate or a proportion. To interpret a count as a proportion, the relevant denominator must also be known and must refer to the same eligible population. Here, the record defines who is eligible for the primary outcome but does not report how many participants met that definition or how many had a negative APTIMA result. The total enrollment of 276 is not a substitute for that outcome-specific denominator.

The outcome title uses the term specificity, while the outcome description specifies a count. In general, specificity is a proportion: the number classified negative among people defined as not having the target condition, divided by the number of people in that reference-negative group. A count may contribute to such an estimate, but it does not alone provide the proportion or its uncertainty. The registry record does not report a specificity estimate or confidence interval.

What is the role of the reference assessment?

Diagnostic measures depend on how the reference condition is defined. In this record, high resolution anoscopy at baseline identifies the participants described as negative for HSIL. APTIMA results are then used to define the negative test outcome. This framing specifies a reference assessment and an index-test result for the primary measure. General diagnostic-statistics interpretation also depends on consistent timing, eligibility, and result handling. The record does not provide further detail about adjudication, indeterminate results, or how missing test results were handled.

How should repeated screening be understood?

The screening schedule lists baseline and follow-up assessments at 6, 12, 18, and 24 months. Repeated assessments can yield multiple observations from the same participant. In general, those observations are not automatically independent: a statistical analysis may need to account for within-participant correlation when it combines repeated results. The registry record does not report whether the primary analysis used follow-up assessments, how repeated observations were handled, or whether the primary outcome was restricted to baseline as its stated timeframe indicates.

The single-group design matters for interpretation. The record identifies one screening group and does not describe randomized allocation to separate comparator groups. A set of tests performed in one study does not itself create a randomized comparison. General comparisons of diagnostic methods may require paired results on the same participants, defined reference outcomes, and a specified method for comparing accuracy. The registry record does not report such a comparative analysis or its statistical procedure.

What do confidence intervals and p-values contribute?

In general, a confidence interval expresses uncertainty around an estimate under a stated statistical method. Its width depends on the data and assumptions; a narrow interval indicates greater precision than a wide interval. A p-value, when used, describes how compatible the observed data are with a specified null model and test assumptions. Neither measure is reported for the primary outcome in the registry record. Without an estimate and uncertainty measure, the precision of the outcome cannot be assessed. A missing p-value is not evidence that a result was statistically significant or nonsignificant.

General statistical planning also distinguishes the target design from a retrospective illustration. The registry record does not report a trial-specific sample-size justification or power calculation. A planning illustration based on a fraction of an observed effect uses assumptions such as the two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are illustration assumptions, not evidence of this study’s design: this study is recorded as single group, with allocation listed as NA. Such calculations are not observed power and should not be read as the trial’s prospective design rationale. A sample size for participants per arm is not directly a description of the enrolled single-group study.

Why can over-dispersion matter?

General count-data methods sometimes assume that variability follows a particular relationship to the mean. Over-dispersion occurs when observed variability is greater than that assumption allows; standard errors may then be too small if the extra variation is ignored. This consideration is relevant only when a suitable count model is used. The primary outcome is described as a participant count, but the registry record does not report a count model, dispersion parameter, or model-based analysis. No claim about over-dispersion in this study can be made.

Overall, statistical method names cannot replace the missing result and analysis details. The available record defines a baseline outcome population, a count, a screening schedule, and a single-group design. It does not report the numerical primary estimate, its denominator, uncertainty, or the procedures used to analyze the outcome.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Screening (HSIL Detection)")
n      <- c(175)
events <- c(116)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Screening (HSIL Detection)  175  116  66.3  58.8  73.2  59.0  72.9  59.0  72.9

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, tests, time points, or comparisons are examined. In general, conducting many statistical tests can increase the chance of at least one apparently notable result unless the analysis plan addresses that issue. The registry record lists five outcome measures and names acceptability of anal cancer screening as a secondary outcome. It does not report the full set of outcome definitions, a hierarchy of hypotheses, an adjustment for multiple testing, or a statistical analysis plan. The handling of multiplicity is therefore not reported in the registry record.

The screening schedule includes baseline and assessments at 6, 12, 18, and 24 months. The primary outcome timeframe is baseline. The record does not state whether the follow-up assessments were analyzed as separate outcomes, combined, or used for other purposes. Without that information, the number of analyses involving time points cannot be determined from the registry entry.

Missing-data handling is also not reported in the registry record. The primary population requires a baseline high resolution anoscopy result and an APTIMA result, but the record does not give the number of participants with both results or explain how unavailable or indeterminate results were treated. It does not describe imputation, exclusion rules, or sensitivity analyses. The enrollment of 276 should not be assumed to equal the primary analysis population.

The record does not identify a general analysis population beyond the primary outcome’s eligibility description. It also lists zero analyses, so no analysis-specific denominator, missing-data procedure, multiplicity adjustment, or result can be verified from the posted record. These omissions limit assessment of how completely the planned outcomes were analyzed; they do not establish that a particular method was or was not used outside the registry entry.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chest pain - cardiac (0.4%), bone infection (0.4%), lung infection (0.4%), dyspnea (0.4%), skin and subcutaneous tissue disorder, other (0.4%).

The registry lists one screening group with 256 participants at risk for serious adverse events and 4 affected by serious adverse events. It lists 256 at risk for other adverse events and 17 affected. The record also lists 1 death. These are descriptive counts in the registry record; they do not by themselves show whether an event was caused by screening or by an associated procedure.

The listed serious-event terms each have a reported value of 0.4%: chest pain - cardiac, bone infection, lung infection, dyspnea, and skin and subcutaneous tissue disorder, other. The record does not explain in this entry whether these terms represent distinct participants, event episodes, or overlapping categories. They should not be added together or interpreted as mutually exclusive groups without further information.

In general, an at-risk count identifies the recorded group used for an adverse-event summary, while an affected count describes participants recorded with an event. The registry does not provide a randomized safety comparator or a causal analysis. It also does not report event timing, severity details beyond the serious-event classification, relatedness assessments, or person-time. The figures therefore describe what was recorded, not comparative risk or causation.

13. What the Result Does, and Does Not, Mean

The record describes a completed screening study in HIV-infected women, with anal cytology, HPV hybrid capture 2, HPV mRNA assays, and OncoHealth HPVE6/E7 oncoprotein scheduled at baseline and at 6, 12, 18, and 24 months. Its primary outcome is a baseline count of participants with negative APTIMA results among those negative for HSIL on high resolution anoscopy and with APTIMA results. This provides a defined statistical question, but the registry record does not report the numerical answer.

The record does not report a primary estimate, denominator, confidence interval, p-value, or analysis result. It therefore does not establish how many eligible participants tested negative, how precise an estimate would be, or whether the screening methods differed. The absence of reported results is not evidence that the tests had identical performance, nor is it evidence that they differed.

The single-group design and allocation listed as NA do not support interpretation as a randomized comparison with a control arm. The record’s description of several screening methods does not establish that each method was compared under a specific statistical procedure. It also does not report enough information to evaluate the secondary acceptability outcome or the handling of missing test results and repeated assessments.

The adverse-event entries describe recorded counts and listed terms, but do not establish causal attribution or comparative safety. In general, registry summaries are most informative when outcome definitions, denominators, analysis methods, and results are all available. Here, the record supports a description of the study design and planned screening schedule, but not a conclusion about diagnostic performance, relative method performance, or causal effects.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between evaluating screening tests and comparing treatments. The listed procedures are diagnostic screening methods, and the primary outcome is a count tied to a reference assessment at baseline. Interpreting test performance requires a clear target population, reference definition, test result, denominator, and an estimate with uncertainty. The registry record gives some of these definitions but does not report the numerical outcome or its precision.

The distinction between a count and a proportion is particularly important. A negative-test count can be informative as a raw number, but a specificity interpretation generally needs the number of reference-negative participants as its denominator. Because the registry does not report that denominator or the count, readers cannot assess the magnitude of the primary measure. The total enrollment cannot resolve this because the primary population is defined by baseline test results.

The design also illustrates why study structure constrains claims. The record identifies a single group and no randomized allocation. Multiple screening methods within a study do not, by themselves, create a randomized comparison or establish comparative accuracy. General comparisons need a defined method, outcome framework, and analysis plan, none of which is reported for a comparative result.

Finally, registry status and statistical evidence answer different questions. The study is marked completed, but the record lists zero analyses and does not report primary results. Completion alone does not reveal the observed data, the uncertainty around them, or how the outcome was analyzed. This distinction helps keep conclusions tied to the evidence actually recorded.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record leaves several trial-specific limitations for statistical interpretation. It does not report the primary outcome count, the number of participants eligible for that outcome, an estimate of specificity, or a confidence interval. The primary outcome is defined for a baseline subgroup with both a reference assessment and APTIMA results, but the size and completeness of that subgroup are not reported.

Although the screening schedule includes baseline and follow-up at 6, 12, 18, and 24 months, the primary outcome timeframe is baseline. The record does not explain whether follow-up outcomes were analyzed, how repeated observations were handled, or whether participants with incomplete follow-up were included in any analysis. Missing-data procedures and analysis populations are not reported in the registry record.

The record lists a single-group model, allocation as NA, and no masking. It does not describe a randomized control comparison, nor does it report a statistical procedure for comparing the screening methods. It also does not report a statistical analysis plan, multiplicity handling, or a trial-specific sample-size justification. These gaps limit evaluation of the analysis strategy and precision.

The primary outcome title refers to specificity of other methods for APTIMA, while its description specifies a count of negative APTIMA results among HRA-negative participants. The record does not report separate accuracy results for each listed screening method, or explain how the title and count relate to any comparative analysis. Safety summaries are also limited: the record does not provide causal attribution or detailed event timing. These limitations restrict interpretation to the recorded design, definitions, and descriptive entries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Anal HPV Tests in Screening for Cell Changes in the Anus in Patients With HIV — NCT01946139.
• Registry record last updated 2023-11-07; status last verified 2023-04.
• Results first posted 2022-09-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01946139 is a completed, single-group study titled “Anal HPV Tests in Screening for Cell Changes in the Anus in Patients With HIV.” The official title is “Screening HIV-Infected Women for Anal Cancer Precursors.” The registry lists an enrollment of 276 and screening at baseline and at 6, 12, 18, and 24 months using anal cytology, HPV hybrid capture 2, HPV mRNA assays, and OncoHealth HPVE6/E7 oncoprotein.

The primary outcome is a baseline count of participants negative for HSIL on APTIMA among those negative on high resolution anoscopy and with APTIMA results. The registry lists five outcome measures and zero analyses, but does not report a numerical primary result or its precision. It also lists acceptability of anal cancer screening as a secondary outcome. Safety entries include 4 participants affected by serious adverse events, 17 affected by other adverse events, and 1 death among the recorded group. These entries do not establish causation.