As virtually all cervical cancers are thought to result from human papillomavirus (HPV) infection, it would be reasonable to consider testing for HPV DNA as a screening test for cervical cancer. There are several issues to consider regarding using HPV DNA testing as a primary screening test. The first is to find a feasible test that detects the optimal number of types of HPV. The current U.S. Food and Drug Administration-approved test, the Hybrid Capture 2 (HC2) detects the presence of 13 types of HPV that have been associated with cervical cancer. The HC2 test is approved to be used in conjunction with the Papanicolaou (Pap) test. The ranges of sensitivity of this test for detecting cervical intraepithelial neoplasia (CIN) 2–3 is from 84% to 95%.[1,2] In a randomized trial using both Pap and HPV testing in random order among women aged 30 to 69 years; sensitivity of HPV was higher than Pap testing, 95% and 55%, respectively. The combination of both HPV and Pap testing had a 100% sensitivity with a referral rate of 7.9%.[2]

Lowered specificity of HPV DNA testing compared with Pap testing, is a second issue to consider. Among women older than 30 years, the Pap test had a 97% specificity compared with 94% for HPV DNA testing.[2] The specificity of HPV DNA testing would likely be lower among women younger than 30 years, because women, especially younger women, may have transient HPV infection that is asymptomatic and of little clinical consequence. Thus, detecting such women would potentially increase unnecessarily the number of follow-up diagnostic workups.

Another issue with this and other screening modalities is the potential for overdiagnosis of cervical lesions that would not progress to cancer. This issue was addressed in a randomized trial comparing screening HPV plus Pap test to Pap test on subsequent high risk cervical lesions or cancer that was conducted in Sweden among women aged 23 to 50 years.[3] Grade 3 cervical lesions and cancer were reduced by 47% at the first incident screening, however, grade 2 lesions detected at a higher rate at the prevalence screen were not followed by a reduction in detection at subsequent screens suggesting that some of the increased diagnosis of grade 2 lesions is due to overdiagnosis.[3] This trial had an average of only 4 years of follow-up, which covered the first incident screening round, thus limiting the assessment of the impact of overdiagnosis and the overall effect of screening on subsequent grade 3 cervical intraepithelial neoplasia and invasive cancer.

The ASCUS/LSIL Triage Study (ALTS) found that HPV testing was most useful in triaging women with the ambiguous atypical squamous cells of undetermined significance (ASCUS) findings on cytologic screening. This trial randomly assigned women with ASCUS to one of three evaluation strategies: immediate colposcopy, triage-to-colposcopy based on HPV results from HC2 testing, and conservative management. The HPV-triage strategy detected about as many cases of CIN 2+ as the immediate-colposcopy strategy, but only 56% of women underwent colposcopy. Thus, the study concluded that HPV testing of the large number of women with ASCUS findings for triage to colposcopy is a more efficient strategy than immediate colposcopy. This strategy was also more efficient than conservative repeat-cytologic testing.[4]

References

1. Hartmann KE, Hall SA, Nanda K, et al.: Screening for Cervical Cancer. Rockville, Md: Agency for Health Research and Quality, 2002. Available online. Last accessed February 20, 2007. 
   
   
2. Mayrand MH, Duarte-Franco E, Rodrigues I, et al.: Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med 357 (16): 1579-88, 2007.  [PUBMED Abstract]
   
   
3. Naucler P, Ryd W, Törnberg S, et al.: Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Engl J Med 357 (16): 1589-97, 2007.  [PUBMED Abstract]
   
   
4. Solomon D, Schiffman M, Tarone R, et al.: Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst 93 (4): 293-9, 2001.  [PUBMED Abstract]
   
   

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