HPV in ASC-US Cytology and Cervical Precancer Risk
HPV in ASC-US Cytology and Cervical Precancer Risk
Of the 958 women with an ASC-US Pap result enrolled into the CLEAR trial who had evaluable AHPV results, 912 (95.2%) also had AHPV-GT results available and defined the analytic group. The mean, median, and range of ages of the 912 women included in this analysis were 34.2, 32, and 21 to 85 years, respectively; women who were hrHPV-positive ASC-US were younger than women who were hrHPV-negative ASC-US (median age, 29.5 years vs 37.1 years, respectively; P < .001). The distribution for race/ethnicity was 46.7% white (non-Hispanic), 21.9% black, 11.7% white (Hispanic), and 20.1% other or unknown. Most women had never smoked (58.7%), had at least one live birth (63.6%), and had ever used oral contraceptives (76.2%) (data not shown).
Table 1 reports the hrHPV and GT results overall, stratified by age, and stratified by site in the 912 women with ASC-US included in this analysis. The percent hrHPV positive was 38.8% overall and decreased in older age groups: 57.0% for 21 to 29 years to 16.7% for 40 years and older (Ptrend < .001). The percent hrHPV positive did not vary significantly by testing site.
While the percentage of GT positive among hrHPV positives did not vary greatly by age (32.7% for 21–29 years, 37.1% for 30–39 years, and 35.6% for ≥40 years), GT-positive women aged 21 to 29 years were more likely to be HPV 16 positive, while women 30 years and older were more likely to be HPV 18/45 positive (odds ratio, 3.8; 95% CI, 1.6–8.8). By comparison, there was little variation in the percent GT positive among hrHPV positives and for which HPV type (16 or 18/45) by site. It was rare to test positive for both HPV 16 and HPV 18/45 (n = 3).
The percent positive for GT, other 11 hrHPV, individual 16 or 18/45 HPV genotypes, and hrHPV positive as well as the percent hrHPV negative with increasing severity of histologically confirmed diagnoses are shown in Table 2. Among hrHPV positives, the high-grade disease (CIN2 +) found among GT positive was marginally more likely to be CIN3/adenocarcinoma in situ (AIS) than among other 11 hrHPV positives (55.8% vs 30.3%, respectively; P = .05). Fifteen of the 33 (45.4%) CIN3/AIS and 12 of the 46 CIN2 (26.1%) were HPV 16 positive.
Of the 893 (93.2%) of 958 women who had a certain histologic diagnosis, absolute risk, relative risk, and positive likelihood ratio were calculated for CIN2 + Table 3 and CIN3/AIS Table 4. Women who tested HPV 16 positive were at the highest absolute risk of CIN2 + (37.0%) and CIN3/AIS (20.5%). Women who were GT positive were at 29.1% risk of CIN2 + and 16.2% risk of CIN3/AIS, which was significantly higher than the risk of CIN2 + (14.3%, P = .001) and risk of CIN3/AIS (4.3%, P < .001) among women who were positive for other 11 hrHPVs.
Finally, the absolute risks of CIN2 + and CIN3/AIS by HPV status for each age group (21–24, 25–29, and 30 years and older) is shown in Figure 2. For all age groups, testing GT positive denoted a subgroup of women who were at higher risk of CIN3/AIS than those who tested other 11 hrHPV positive (16.7% vs 4.8%, P = .04 for 21–24 years; 14.3% vs 6.3%, P = .2 for 25–29 years; and 17.4% vs 2.4%, P = .004 for 30 years and older). Similar differences were noted for CIN2 + except for women aged 25 to 29 years, in whom there was a higher proportion of CIN2 than in other subgroups.
(Enlarge Image)
Figure 2.
Absolute risks of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2 +) and cervical intraepithelial neoplasia grade 3 (CIN3) or adenocarcinoma in situ (AIS) (CIN3/AIS) among 893 women with an atypical squamous cells of undetermined significance Papanicolaou result by high-risk human papillomavirus (hrHPV) status: positive for HPV 16, 18, and/or 45 genotype (GT); GT negative but positive for other hrHPV; or hrHPV negative.
Results
Of the 958 women with an ASC-US Pap result enrolled into the CLEAR trial who had evaluable AHPV results, 912 (95.2%) also had AHPV-GT results available and defined the analytic group. The mean, median, and range of ages of the 912 women included in this analysis were 34.2, 32, and 21 to 85 years, respectively; women who were hrHPV-positive ASC-US were younger than women who were hrHPV-negative ASC-US (median age, 29.5 years vs 37.1 years, respectively; P < .001). The distribution for race/ethnicity was 46.7% white (non-Hispanic), 21.9% black, 11.7% white (Hispanic), and 20.1% other or unknown. Most women had never smoked (58.7%), had at least one live birth (63.6%), and had ever used oral contraceptives (76.2%) (data not shown).
Table 1 reports the hrHPV and GT results overall, stratified by age, and stratified by site in the 912 women with ASC-US included in this analysis. The percent hrHPV positive was 38.8% overall and decreased in older age groups: 57.0% for 21 to 29 years to 16.7% for 40 years and older (Ptrend < .001). The percent hrHPV positive did not vary significantly by testing site.
While the percentage of GT positive among hrHPV positives did not vary greatly by age (32.7% for 21–29 years, 37.1% for 30–39 years, and 35.6% for ≥40 years), GT-positive women aged 21 to 29 years were more likely to be HPV 16 positive, while women 30 years and older were more likely to be HPV 18/45 positive (odds ratio, 3.8; 95% CI, 1.6–8.8). By comparison, there was little variation in the percent GT positive among hrHPV positives and for which HPV type (16 or 18/45) by site. It was rare to test positive for both HPV 16 and HPV 18/45 (n = 3).
The percent positive for GT, other 11 hrHPV, individual 16 or 18/45 HPV genotypes, and hrHPV positive as well as the percent hrHPV negative with increasing severity of histologically confirmed diagnoses are shown in Table 2. Among hrHPV positives, the high-grade disease (CIN2 +) found among GT positive was marginally more likely to be CIN3/adenocarcinoma in situ (AIS) than among other 11 hrHPV positives (55.8% vs 30.3%, respectively; P = .05). Fifteen of the 33 (45.4%) CIN3/AIS and 12 of the 46 CIN2 (26.1%) were HPV 16 positive.
Of the 893 (93.2%) of 958 women who had a certain histologic diagnosis, absolute risk, relative risk, and positive likelihood ratio were calculated for CIN2 + Table 3 and CIN3/AIS Table 4. Women who tested HPV 16 positive were at the highest absolute risk of CIN2 + (37.0%) and CIN3/AIS (20.5%). Women who were GT positive were at 29.1% risk of CIN2 + and 16.2% risk of CIN3/AIS, which was significantly higher than the risk of CIN2 + (14.3%, P = .001) and risk of CIN3/AIS (4.3%, P < .001) among women who were positive for other 11 hrHPVs.
Finally, the absolute risks of CIN2 + and CIN3/AIS by HPV status for each age group (21–24, 25–29, and 30 years and older) is shown in Figure 2. For all age groups, testing GT positive denoted a subgroup of women who were at higher risk of CIN3/AIS than those who tested other 11 hrHPV positive (16.7% vs 4.8%, P = .04 for 21–24 years; 14.3% vs 6.3%, P = .2 for 25–29 years; and 17.4% vs 2.4%, P = .004 for 30 years and older). Similar differences were noted for CIN2 + except for women aged 25 to 29 years, in whom there was a higher proportion of CIN2 than in other subgroups.
(Enlarge Image)
Figure 2.
Absolute risks of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2 +) and cervical intraepithelial neoplasia grade 3 (CIN3) or adenocarcinoma in situ (AIS) (CIN3/AIS) among 893 women with an atypical squamous cells of undetermined significance Papanicolaou result by high-risk human papillomavirus (hrHPV) status: positive for HPV 16, 18, and/or 45 genotype (GT); GT negative but positive for other hrHPV; or hrHPV negative.
