TY - JOUR
T1 - A study of type-specific HPV natural history and implications for contemporary cervical cancer screening programs
AU - Demarco, Maria
AU - Hyun, Noorie
AU - Carter-Pokras, Olivia
AU - Raine-Bennett, Tina R.
AU - Cheung, Li
AU - Chen, Xiaojian
AU - Hammer, Anne
AU - Campos, Nicole
AU - Kinney, Walter
AU - Gage, Julia C.
AU - Befano, Brian
AU - Perkins, Rebecca B.
AU - He, Xin
AU - Dallal, Cher
AU - Chen, Jie
AU - Poitras, Nancy
AU - Mayrand, Marie Helene
AU - Coutlee, Francois
AU - Burk, Robert D.
AU - Lorey, Thomas
AU - Castle, Philip E.
AU - Wentzensen, Nicolas
AU - Schiffman, Mark
N1 - Publisher Copyright:
© 2020
PY - 2020/5
Y1 - 2020/5
N2 - Background: HPV testing is replacing cytology for cervical cancer screening because of greater sensitivity and superior reassurance following negative tests for the dozen HPV genotypes that cause cervical cancer. Management of women testing positive is unresolved. The need for identification of individual HPV genotypes for clinical use is debated. Also, it is unclear how long to observe persistent infections when precancer is not initially found. Methods: In the longitudinal NCI-Kaiser Permanente Northern California Persistence and Progression (PaP) Study, we observed the clinical outcomes (clearance, progression to CIN3+, or persistence without progression) of 11,573 HPV-positive women aged 30–65 yielding 14,158 type-specific infections. Findings: Risks of CIN3+ progression differed substantially by type, with HPV16 conveying uniquely elevated risk (26% of infections with seven-year CIN3+ risk of 22%). The other carcinogenic HPV types fell into 3 distinct seven-year CIN3+ risk groups: HPV18, 45 (13% of infections, risks >5%, with known elevated cancer risk); HPV31, 33, 35, 52, 58 (39%, risks >5%); and HPV39, 51, 56, 59, 68 (23%, risks <5%). In the absence of progression, HPV clearance rates were similar by type, with 80% of infections no longer detected within three years; persistence to seven years without progression was uncommon. The predictive value of abnormal cytology was most evident for prevalent CIN3+, but less evident in follow-up. A woman's age did not modify risk; rather it was the duration of persistence that was important. Interpretation: HPV type and persistence are the major predictors of progression to CIN3+; at a minimum, distinguishing HPV16 is clinically important. Dividing the other HPV types into three risk-groups is worth considering.
AB - Background: HPV testing is replacing cytology for cervical cancer screening because of greater sensitivity and superior reassurance following negative tests for the dozen HPV genotypes that cause cervical cancer. Management of women testing positive is unresolved. The need for identification of individual HPV genotypes for clinical use is debated. Also, it is unclear how long to observe persistent infections when precancer is not initially found. Methods: In the longitudinal NCI-Kaiser Permanente Northern California Persistence and Progression (PaP) Study, we observed the clinical outcomes (clearance, progression to CIN3+, or persistence without progression) of 11,573 HPV-positive women aged 30–65 yielding 14,158 type-specific infections. Findings: Risks of CIN3+ progression differed substantially by type, with HPV16 conveying uniquely elevated risk (26% of infections with seven-year CIN3+ risk of 22%). The other carcinogenic HPV types fell into 3 distinct seven-year CIN3+ risk groups: HPV18, 45 (13% of infections, risks >5%, with known elevated cancer risk); HPV31, 33, 35, 52, 58 (39%, risks >5%); and HPV39, 51, 56, 59, 68 (23%, risks <5%). In the absence of progression, HPV clearance rates were similar by type, with 80% of infections no longer detected within three years; persistence to seven years without progression was uncommon. The predictive value of abnormal cytology was most evident for prevalent CIN3+, but less evident in follow-up. A woman's age did not modify risk; rather it was the duration of persistence that was important. Interpretation: HPV type and persistence are the major predictors of progression to CIN3+; at a minimum, distinguishing HPV16 is clinically important. Dividing the other HPV types into three risk-groups is worth considering.
KW - HPV genotype
KW - HPV outcome, Clearance
KW - Persistence
KW - Progression
UR - http://www.scopus.com/inward/record.url?scp=85083728741&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083728741&partnerID=8YFLogxK
U2 - 10.1016/j.eclinm.2020.100293
DO - 10.1016/j.eclinm.2020.100293
M3 - Article
AN - SCOPUS:85083728741
SN - 2589-5370
VL - 22
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 100293
ER -