At baseline, 14.2% (95% CI, 13.7% to 14.7%) of the women tested HR-HPV positive by HC2, and 5.4% (95% CI, 5.1% to 5.8%) of women had a positive Pap; of the 12,461 women who were age 30 years or older and for whom co-testing with HR-HPV and Pap is now a screening option, 8.7% (95% CI, 8.2% to 9.2%) tested HR-HPV positive, and 4.3% (95% CI, 4.0% to 4.7%) had a positive Pap. The age group–specific percent positive (prevalence) by HR-HPV and cytology is shown in Appendix Figure A1 (online only). As expected, the positive HR-HPV tests and positive Paps were highest in women younger than age 30 years and were two-fold greater those occurring in women age 30 to 34 years. At all ages, approximately half of the women who tested HR-HPV positive had a concurrent positive Pap.
There were 396 patient cases of CIN2+ and 199 of CIN3+ diagnosed over the 18 years of the study. More patient cases of CIN2+ (215 v 136; P < .001) and CIN3+ (112 v 65; P < .001) occurred after a baseline HR-HPV–positive result versus positive Pap (). Among HR-HPV–positive women, approximately half of those with CIN2+ and CIN3+ had concurrent negative baseline Pap.
Worst Diagnosis Over 18-Year Follow-Up of Approximately 20,000 Women at Kaiser Permanente Northwest (Portland, OR) by Baseline Test Results
shows the risk stratification for CIN2+ (A) and CIN3+ (B) achieved by the baseline HR-HPV and Pap tests separately. A positive Pap strongly predicted disease within the first 2 years, whereas an HR-HPV–positive test continued to predict those who were at risk until the end of the study. For example, HR-HPV–positive women were more likely to be diagnosed with CIN2+ (P < .001) and CIN3+ (P = .004) 10 to 18 years after enrollment compared with HR-HPV–negative women. In that same time period, women with a positive Pap were not more likely to be diagnosed with CIN2+ (P = .8) or CIN3+ (P = 1.0) than women with a negative Pap.
Fig 2. The risk of a diagnosis of (A) cervical intraepithelial neoplasia (CIN) grade 2 or more severe (CIN2+) and (B) CIN grade 3 or more severe (CIN3+) after a baseline test for human papillomavirus (HPV) and by the clinical center Papanicolaou (Pap) test. (more ...)
In a complimentary fashion, a one-time negative HR-HPV test at enrollment provided greater reassurance over the 18-year follow-up than a one-time negative Pap against CIN2+ (1.85% v 2.47%) and CIN3+ (0.90% v 1.27%). By comparison, cumulative incidence was 1.73% for CIN2+ and 0.83% for CIN3+ after one-time HPV and Pap tests that were both negative.
lists the 18-year cumulative detection of CIN2+ and CIN3+ for years 0 to 4, 5 to 9, and 10 to 18 by combined baseline HR-HPV and Pap test results. The 18-year CIRs of CIN3+ for HR-HPV positive/Pap positive, HR-HPV positive/Pap negative, HR-HPV negative/Pap positive, and HR-HPV negative/Pap negative were 9.91%, 3.90%, 3.01%, and 0.72%, respectively. Similar patterns of risk stratification were observed for CIN2+, with a range of 18-year CIR of 21.23% for HR-HPV positive/Pap positive to 1.42% for HR-HPV negative/Pap negative.
Cumulative Detection of CIN2+ or CIN3+ After Baseline Test for HR-HPV and Clinical Center Pap Test
We examined the 18-year risk of CIN3+ by enrollment screening results stratified by age groups: < 30 years (median age, 24 years), 30 to 39 years (median age, 34 years), and ≥ 40 years (median age, 47 years; ). There was a greater cumulative incidence of CIN3+ among those women age younger than 30 and age 30 to 39 years who tested HPV positive/Pap normal than among those age 40 years or older. A similar age-related effect was noted in the HPV-negative/Pap-normal populations.
Cumulative Detection of CIN3 or CIN3+ After Baseline Test for HR-HPV and Clinical Center Pap Test Stratified by Enrollment Age Group
After negative HPV and Pap tests in women age 30 years or older (n = 12,461), the 3-year risks, relevant to past cotesting screening guidelines, of CIN2+ and CIN3+ were 0.23% and 0.08%, respectively. If the screening intervals were extended to 5 years according to current cotesting screening guidelines,26a
the risks were 0.36% and 0.16%, respectively. Of the 37 patient cases of CIN3+ diagnosed in this subgroup, only five (14%) were diagnosed within 3 years and 13 (35%) within 5 years.
Finally, we wanted to look at the 18-year risks of CIN2+ and CIN3+ for different combinations of Pap interpretations and HPV risk groups ( ). In general, cervical cancer risk increased with more severe Pap interpretations and higher-risk HPV genotypes. Notably, women who tested HPV16 positive had a similar or higher 18-year CIR than women with any Pap interpretation other than HSIL.
18-Year Cumulative Detection of CIN2+ or CIN3+ by Baseline Hierarchic HPV Status and Pap Test Results