Draft Research Plan
Anal Cancer: Screening
December 08, 2022
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
- Does screening for anal cancer in high-risk persons change all-cause mortality, anal cancer–specific mortality or morbidity, or quality of life?
- What is the accuracy of screening tests for anal cancer?
- What are the harms associated with screening for anal cancer?
- What is the effectiveness of treatment of anal intraepithelial neoplasia and early-stage (Stage I), localized anal cancer?
- What are the harms associated with treatment of anal intraepithelial neoplasia, high-grade squamous intraepithelial lesions, and early-stage (Stage I), localized anal cancer?
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
- Does screening for anal cancer in high-risk persons change the incidence of anal cancer and the distribution of cancer types and stages (i.e., stage shift)?
- What is the magnitude of change in all-cause and anal cancer–specific mortality that results from a specified change in anal cancer incidence (and change in distribution of anal cancer stages [i.e., stage shift]) after screening?
- What risk assessment tools are available for use in primary care to identify adults at increased risk for anal cancer?
To the extent possible, we plan to describe the population, screening, and intervention characteristics of the included studies. Data on population characteristics will help us explore the degree to which the findings are representative of persons at risk for anal cancer as well as investigate potential differences in benefit and harms by different population groups. These groups include, but are not limited to, categorizations by age; racial, ethnic, and cultural identity; behavioral risk factors; and chronic health conditions.
The Proposed Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions.
| Category | Include | Exclude |
|---|---|---|
| Populations | KQs 1, 3: Asymptomatic adults (age ≥18 years) with an increased risk of anal cancer (e.g., persons living with HIV, men who have sex with men, persons engaging in anoreceptive intercourse, and immunocompromised persons)
KQ 2: Studies of adults with AIN are also eligible KQs 4, 5: Adults with AIN or early-stage (Stage I) anal cancer All KQs: Specific populations of interest include persons living with HIV, men who have sex with men, persons engaging in anoreceptive intercourse, and immunocompromised persons |
KQs 1, 3: Children; persons with symptoms of anal cancer; other populations in which testing for anal cancer may be considered part of disease management, such as persons with HPV-related cancers and cancer precursors (i.e., HSILs)
KQ 2: Children KQs 4, 5: Children; persons with nonprimary anal cancer or other than Stage I anal cancer |
| Screening | KQs 1, 3: Anal cytology, HPV testing, or anal cytology with HPV co-testing; studies may also incorporate visual inspection and digital anorectal examination. Anal cytology involves a Pap test sampling cells inside the anus. These screening tests may be followed by other tests for diagnostic evaluation, including anoscopy or proctoscopy, HRA, ultrasound (endoanal or endorectal), or biopsy
KQ 2: Anal cytology, HPV testing, or anal cytology with HPV co-testing |
No screening; other screening modalities |
| Interventions | KQs 4, 5: Surgical excision, ablation (e.g., chemical ablation with trichloroacetic acid), fulguration, laser therapy, topical immunomodulator therapy (e.g., imiquimod topical cream), or topical 5-fluorouracil | KQs 4, 5: Chemotherapy, radiation therapy, or natural therapies |
| Comparisons | KQs 1, 3: No screening, usual care
KQ 2: Biopsy KQs 4, 5: No treatment, usual care, or no comparison |
Studies without a comparison group; comparative effectiveness studies (head-to-head studies comparing treatments) |
| Outcomes | KQ 1: All-cause mortality, anal cancer–specific mortality and morbidity, and quality of life
KQ 2: Sensitivity and specificity of anal cytology with or without HPV co-testing KQ 3: False-positive results, irritation, pain, bleeding, overdiagnosis, psychosocial harms, and additional tests and subsequent harms (e.g., biopsy causing an adverse event) KQ 4: Incidence of anal cancer (all stages), distribution of cancer types and stages, all-cause mortality, anal cancer–specific mortality and morbidity, and quality of life KQ 5: Irritation, pain, bleeding, erosions, anal fissures, anal stenosis, altered bowel functioning (e.g., incontinence), altered urinary functioning, and altered sexual functioning |
Cost |
| Study designs | Controlled trials are eligible for all KQs
KQ 2: Studies evaluating accuracy are also eligible KQs 3, 5 (harms): Prospective cohort studies and case-control studies are also eligible |
All other study designs |
| Study duration | Any length | |
| Settings | Published in or after 2000 | Published before 2000 |
| Countries | Studies conducted in countries categorized as “Very High” on the Human Development Index (as defined by the United Nations Development Program) | Studies conducted in countries that are not categorized as “Very High” on the Human Development Index |
| Language | English | Non-English |
| Study quality | Good or fair | Poor (according to design-specific USPSTF criteria) |
Abbreviations: AIN=anal intraepithelial neoplasia; HIV=human immunodeficiency virus HPV=human papillomavirus; HSIL= high-grade squamous intraepithelial lesion; HRA=high-resolution anoscopy; KQ=key question; USPSTF=U.S. Preventives Services Task Force.