Six hundred twenty four women were enrolled in the Natural History of HPV in Teens study. Five hundred thirty seven had provided both cervical and vaginal samples between 2000 and 2006 and were eligible for this analysis. Mean follow-up time was 996 days (range 42 to 1785 days; standard deviation (SD) 481.6). Demographic characteristics of the 537 women are given in . The median number of lifetime sexual partners is 3. The majority of initial infections were incident (80%). Thirty-eight (7.1%) women had multiple types on initial SC and 46 (8.6%) on initial CC-L visit. From these women, we had 4330 CC-L and 3080 SC samples. If we assumed all women had all visits, we would have expected 4,539 CC-L samples and 4,539 SC samples. However, there were 209 missing CC-L samples and 1,459 missing SC samples. Per the imputation criteria, we imputed 99 CC-L (2.1%) HPV results of which the majority (93%) of the imputations were negative. We imputed 913 SC samples of which the majority (96%) of the imputations were negative. The probability of being negative between two negatives was close to 100%.
Demographics Characteristics (N=537)
In the longitudinal cohort, the most common high-risk HPV infections detected among the 4,330 CC-L samples were 16, 18, 39, 51, 52, 53, 59, 66 and 68 (). The same 9 were also found to be the most common high-risk types from the 3,080 SC samples. Of the 13 types listed in , HPV 16 was found to be the most common initial (defined as first ever detected whether prevalent or incident) infection detected by cervical or vaginal sampling. The most common low risk types were 84, 6, 89, and 62 for both methods.
The Frequency of High-Risk and Low-Risk HPV Types Detected in Clinician Lavage- and Self-Collected Samples
Comparison of time-to-clearance for combined HR and LR HPV types and specific HPV types between CC-L and SC samples
Among all samples and all women, no significant differences were found for all 18 HR HPV types (inclusive of the probable HR types) (p=0.24) or 4 LR HPV types (p=0.84) (). When we excluded the 6 probable HR types, similar observations were made for the 12 HR HPV types (p=.22) (curve not shown). P values are adjusted for age and prevalent infection.
Comparison of type-specific time-to-clearance for 18 HR-HPV types combined and 4 LR HPV types combined between self-collected (black line) and clinician-collected lavage (gray line) samples
We next examined differences between 13 specific HPV types with CC-L frequencies greater than 1.0%. Among all samples and all women, no significant differences were found between clearance time distributions from CC-L and SC samples for each of the HPV types. A trend was found for HPV 66 (p=0.09) (). HPV 66 appeared to clear slower by SC means compared to CC-L. The above analysis was independent of sampling method results. To examine the time-to-clearance within a woman, we used the second approach which started with an initial CC-L positive test and compared time-to-clearance by sampling method. We again found no significant differences in to time-to-clearance for any HPV type (). A trend was found for HPV 16 (p= 0.08) which showed that CC-L samples cleared slower than SC samples. We also examined time-to-clearance between methods starting with a positive SC sample and again found no difference (p values ranged from 0.16 to 0.97) (data not shown).
Comparison of type-specific time-to-clearance between self-collected (black line) and clinician-collected lavage (gray line) samples
Time-to-clearance of specific HPV types among CC-L samples and among SC samples
The third approach to compare sampling method was to examine patterns of HPV types (faster, slower) within a sampling method and see if those patterns were also present in the other method. Among the CC-L samples, HPV 6, 66 and 18 had the shortest time-to-clearance with 97%, 95% and 95%, respectively, showing clearance by 1 year. Following these 3 types, HPV 84, 39 and 89 were the second fastest group to clear. The slowest to clear by one year were HPV 62, 68, 59 and 16. HPV 6 was statistically significantly faster to clear than HPV 16, 39, 51, 52, 53, 59, and 68. Among HR HPV types, HPV 66 was faster to clear than HPV 16, 53, 59 and 68 and HPV 18 was faster than 59 and 68 with a trend for HPV 16. HPV 39 was also found to clear faster than HPV 59 and 68. HPV 16 was similar to most other oncogenic HPV types except 66 as noted. Among the LR types, HPV6 was also faster to clear than HPV 62 and 89, but not HPV 84. Curves for time-to-clearance of CC-L samples are shown in ; times-to-clearance and Hazard ratios for CC-L samples are summarized in and , respectively.
Comparison of HPV type-specific clearance among clinician-collected lavage samples and self-collected samples
Clearance rate of 13 specific HPV types among 537 women using clinician-collected lavage and self-collected samples
Hazard ratio* for time-to-clearance between HPV types for clinician-collected lavage samples and self-collected samples
Similar patterns were seen among the SC samples. The top 6 fastest types to clear by 1 year were the same as seen among the CC-L samples (in order starting with fastest: HPV 6, 84, 89, 39, 18 and 66). The slowest to clear were also similar (in order starting with the slowest: HPV 62, 16 and 68). Statistical comparisons found that HPV 6 was significantly faster than HPV 16, 52 and 59 with trends for HPV 53 and 68. Among the high risk types, HPV 39 was faster to clear than HPV 16, 51, 52, 53, 59, and 68 with a trend for HPV 18. Among the high-risk HPV types, no statistically significant differences were seen for HPV 18 or HPV 66, as seen with the CC-L samples. HPV 16 again was similar to the other high-risk types except HPV 39. Among the low-risk types, HPV 6 was faster than HPV 62, but no difference was seen for HPV 84 and 89. Curves for time-to-clearance for SC samples are shown in ; times-to-clearance and Hazard ratios for SC samples are summarized in and , respectively. In a separate analysis, we compared HPV 16 time-to-clearance to all the other oncogenic types combined and found no statistical difference for either the SC or CC-L samples (data not shown).
Comparison of flanking CC-L and SC samples
The previous analysis focused on the natural history with repeated measures. We were also interested in examining how often CC-L and SC samples correlated in proximity to time. This analysis focused on high-risk types only and no imputed data were used for this analysis.
First, we examined the probability that the intervening SC sample was positive if 2 consecutive CC-L samples were both positive for the same type. If 2 consecutive CC-L samples were positive for the same type, 69% (range 53% − 88%) of intervening SC samples were also positive for the same type (+++). HPV 18 had the highest probability (88%) and HPV 53 had the lowest (53%). In comparison, if 2 consecutive SC samples were positive for the same type, 61% (range 30% – 77%) of the intervening CC-L samples were positive (p = 0.02). HPV 59 had the highest (77%), and HPV 39 had the lowest (30%). Results for specific HPV types are shown in ; columns A and B. If 2 consecutive samples were negative, whether CC-L or SC, the intervening sample was almost always likely to be negative. The probability was over 99% for all types (data not shown).
Comparison between flanking clinician-collected lavage and self-collected samples for 9 high-risk HPV types
We next examined the rate of SC positive samples if we used repeated SC sampling. Among 2 consecutive positive CC-L samples, the rate of matching positive tests was higher if two consecutive SC samples were examined; 90.4% (range 75%–100%) of positive CC-L specimens had at least one flanking SC sample [either sandwiched (+
+) or before (
+-+-) or after (-+-+
) positive for the same type. The rate of matching positive tests was also higher when examining the inverse relationship. Among 2 consecutive positive SC samples, 80.3% (range 56% to 95%) of positive SC samples had at least one flanking CC-L sample (either sandwiched or before or after) positive for the same type. Results for specific HPV types are shown in ; columns C and D.