Several studies documented the usefulness of HPV testing in the assessment of ASC-US Pap test results (74–76). These studies demonstrate that HPV testing can identify 90% of the patients with CIN 2 or 3 lesions. To compare the aforementioned triage method in a prospective, randomized fashion, the NCI funded an ASC-US/LSIL Triage Study (ALTS) (77). Patients with ASC-US or LSIL were randomized to three triage arms: (i) immediate colposcopy, (ii) HPV test, and (iii) conservative management by repeat Pap test. There were 1,163 women in the immediate colposcopy group, and 14 refused the examination. The results of colposcopy are assumed to reﬂect the prevalent disease rates, which were as follows: CIN 1, 14.3%; CIN 2, 16.1%; and CIN 3, 5%. Thus, 75% of the women with ASC-US had negative colposcopy results and either did not have a biopsy (25%) or had a biopsy with negative results. The HPV test results were positive in 56.1% of the patients, and 6.1% of the patients did not return for colposcopy. Of the 494 who underwent colposcopy, the results were as follows: CIN 1, 22.5%; CIN 2, 11.9%; and CIN 3, 15.6%. The sensitivity of HPV test was 95.9% for the detection of CIN 2 and 96.3% for the detection of CIN 3.
In the conservatively managed group, only one follow-up Pap test was reported. To be effective, Pap testing must be done every 6 months. Despite this, the results of the single follow-up Pap test were included. Using a cutoff that includes any positive finding of ASC-US or greater, the sensitivity is 85% for CIN 2 and 85.3% for CIN 3, with 58.6% of patients being referred for colposcopy. If LSIL is used as a cutoff, 26.2% of the patients are referred, with sensitivity of 64.0% for both CIN 2 and 3. Using HSIL as the cutoff, 6.9% are referred, and the sensitivity falls to 44%. The conclusion of the ALTS trial is that HPV triage is highly sensitive in identifying CIN 2 and 3 lesions and that it cuts the rate of referral for colposcopy by approximately one-half (78). When mathematical models are used to simulate the natural history of HPV and cervical cancer in a cohort of U.S. women, a 2-to 3-year screening strategy that uses cytologic assessment in combination with either HPV DNA testing or reﬂex HPV testing appears more effective and less costly in reducing the rate of cancer than annual conventional cytology (79).
The cytologic diagnosis of LSIL is reproducible and accounts for 1.6% of cytologic diagnoses (68). About 75% of the patients have CIN, with 20% being CIN 2 or 3 (69–71). These patients require additional evaluation. The ALTS trial closed the HPV test arm early because the HPV positivity rate was 82% and was not a valid discriminator in determining the presence of disease. The ALTS trial found that a cytology interpretation of LSIL is associated with a 25% risk of histologic CIN 2 or 3 within 2 years. No effective triage strategy was identified to spare many women from colposcopic referral without increasing their risk of CIN 3 and invasive carcinoma (80). Guidelines confirm the validity of the current practice of performing colposcopy to evaluate a single LSIL result (75).
High-Grade Squamous Any woman with a cytologic specimen suggesting the presence of HSIL should undergo