TY - JOUR
T1 - Risk of precancer determined by HPV genotype combinations in women with minor cytologic abnormalities
AU - Gage, Julia C.
AU - Schiffman, Mark
AU - Solomon, Diane
AU - Wheeler, Cosette M.
AU - Gravitt, Patti E.
AU - Castle, Philip E.
AU - Wentzensen, Nicolas
PY - 2013/6
Y1 - 2013/6
N2 - Background: Studies suggest that testing for individual human papillomavirus (HPV) genotypes can improve risk stratification in women with minor cytologic abnormalities. We evaluated genotyping for HPV16, HPV16/18, and HPV16/18/45 in carcinogenic HPV-positive women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology. Methods: For women enrolled in the ASCUS-LSIL Triage Study (ALTS), we calculated the age-stratified (<30 and 30+years) positivity and cumulative risk over two years of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) when testing positive or negative for three genotype combinations: HPV16, HPV16/18, and HPV16/18/45. Results: Among women with ASCUS cytology, HPV16 positivity was 17.1% and increased to 22.0% (P < 0.001) for HPV16/18 and 25.6% (P < 0.001) for HPV16/18/45. Among women with LSIL cytology, HPV16 positivity was 21.1% and increased to 30.0% (P < 0.001) for HPV16/18 and 34.0% (P = 0.017) for HPV16/18/45. Regardless of cytology and age group, the greatest risk difference between test positives and test negatives was observed for HPV16 with decreasing risk stratification for HPV16/18 and HPV16/18/45. However, testing negative for any of the three combinations while being positive for another carcinogenic type still implied a two-year risk of CIN3+ of 7.8% or more. Conclusions: Although genotyping for HPV16, 18, and 45 provided additional risk stratification in carcinogenic HPV-positive women with minor cytologic abnormalities, the risk among genotype-negative women was still high enough to warrant immediate colposcopy referral. Impact: HPV genotyping in HPV-positive women with minor cytologic abnormalities will likely not alter clinical management. Adding HPV45 to genotyping assays is not warranted.
AB - Background: Studies suggest that testing for individual human papillomavirus (HPV) genotypes can improve risk stratification in women with minor cytologic abnormalities. We evaluated genotyping for HPV16, HPV16/18, and HPV16/18/45 in carcinogenic HPV-positive women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology. Methods: For women enrolled in the ASCUS-LSIL Triage Study (ALTS), we calculated the age-stratified (<30 and 30+years) positivity and cumulative risk over two years of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) when testing positive or negative for three genotype combinations: HPV16, HPV16/18, and HPV16/18/45. Results: Among women with ASCUS cytology, HPV16 positivity was 17.1% and increased to 22.0% (P < 0.001) for HPV16/18 and 25.6% (P < 0.001) for HPV16/18/45. Among women with LSIL cytology, HPV16 positivity was 21.1% and increased to 30.0% (P < 0.001) for HPV16/18 and 34.0% (P = 0.017) for HPV16/18/45. Regardless of cytology and age group, the greatest risk difference between test positives and test negatives was observed for HPV16 with decreasing risk stratification for HPV16/18 and HPV16/18/45. However, testing negative for any of the three combinations while being positive for another carcinogenic type still implied a two-year risk of CIN3+ of 7.8% or more. Conclusions: Although genotyping for HPV16, 18, and 45 provided additional risk stratification in carcinogenic HPV-positive women with minor cytologic abnormalities, the risk among genotype-negative women was still high enough to warrant immediate colposcopy referral. Impact: HPV genotyping in HPV-positive women with minor cytologic abnormalities will likely not alter clinical management. Adding HPV45 to genotyping assays is not warranted.
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U2 - 10.1158/1055-9965.EPI-12-1455
DO - 10.1158/1055-9965.EPI-12-1455
M3 - Article
C2 - 23603204
AN - SCOPUS:84879014443
SN - 1055-9965
VL - 22
SP - 1095
EP - 1101
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 6
ER -