The most effective strategies for screening for cervical cancer maximize the benefits and minimize the potential for harm, concluded a study evaluating 10 cervical cancer screening strategies.1
There are numerous strategies to test for cervical cancer, from cytology alone to the new cobas human papillomavirus (HPV) test, which detects pooled high-risk HPV genotypes and provides separate results for HPV16 and HPV18. The current standard of screening for high-grade cervical cancer involves cytology with HPV triage of atypical squamous cells of undetermined significance (ASC-US) and referral of all women with HPV-positive ASC-US or low-grade squamous intraepithelial lesion or greater to colposcopy. However, it is unknown whether this is the optimal screening method, which would balance the benefits of screening against any potential harm (unnecessary colposcopy).
The most widely used cervical cancer screening strategy in the United States is the aforementioned “current standard,” which the researchers used as the comparator for 9 other cervical cancer screening strategies (Table). A total of 34,254 women aged 30 years or older who underwent some form of cervical cancer screening were eligible for this analysis. All participants were from the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study.
In general, screening strategies that had a higher sensitivity also were more likely to be associated with higher rates of referral to colposcopy. The screening strategies that were based on cytology alone or as the only reflex test tended to have the lowest sensitivity for the detection of cervical intraepithelial neoplasia grade 2 (CIN2) or greater or CIN3 or greater.
The study authors identified four strategies that are attractive in terms of a benefit-versus-harm analysis (strategies 4, 5, 9, and 10). These strategies all use HPV testing with genotyping for HPV 16 and HPV 18, and 2 of these strategies involve cotesting. Of all the strategies evaluated, however, strategy 5 and strategy 9 seem to optimize the balance between sensitivity and specificity (see Table).
“Strategies that maximize early detection of CIN3 or more severe without excessive increases in initial screening tests and colposcopies, yet also identify women of intermediate risk in need of 12 month follow-up, would appear to provide optimal balance between benefit and harms,” concluded the study authors.
- Compared with cytology-based strategies, cervical cancer screening tests that involve high-risk HPV testing as the primary test have greater sensitivity for detecting high-grade cervical disease.
- Of 10 screening strategies studies, 4 strategies that screen initially with HPV testing with genotyping for HPV 16 and HPV 18 seem to have the best balance between benefit and harm.
- The 2 best screening strategies among the 4 strategies with an appealing benefit-vs-harm analysis also screen with cytology.
|Strategy||No. of Colposcopies||Sensitivity, %||No. of Initial Tests Performed|
|1. Cytology with reflex HPV (ASC-US Triage)||816||56.1||35,546|
|2. Cytology alone||1644||57.7||34,254|
|3. Cotesting with reflex for ASC-US||816||56.1||68,508|
|4. Cotesting with genotyping and cytology triage: HPV 16/18 and ASC-US HPV+ threshold||1202||76.2||68,508|
|5. Cotesting with genotyping and cytology triage: HPV 16/18 and LSIL threshold*||1030||70.9||68,508|
|6. HPV alone||2341||89.9||34,254|
|7. HPV with cytology triage||596||51.9||37,126|
|8. HPV with genotyping triage||580||53.4||34,254|
|9. HPV with genotyping and reflex cytology: ASC-US threshold*||982||72.0||36,423|
|10. HPV with genotyping and cytology (LSIL cut-off) triage||810||66.7||36,423|
Italicized strategies have the most attractive benefit-vs-harm analysis.
*Most optimal screening strategies.
From Cox JT et al. Am J Obstet Gynecol. 2013.1