Evaluation of antibody response to human papillomavirus early proteins in women in whom cervical cancer developed 1 to 20 years later.
OBJECTIVE
Infection with oncogenic human papillomaviruses (HPVs) is the most important cause of cervical cancer worldwide. After infection there is a long latency period of at least 10 to 15 years during which cervical cancer develops in a small proportion of originally infected women. Up to 50% of these women have at diagnosis antibodies to the HPV oncoproteins E6 and E7, which are rarely found among healthy women. Our purpose was to evaluate whether antibodies to HPV16 and HPV18 E6 and E7 proteins are useful for early diagnosis of cervical cancer by measuring the antibody response in women in whom cervical cancer later developed.


METHODS
A joint serum bank of 550,000 Swedish, Norwegian, and Finnish women was followed up for 0.5 to 20 years, after which 178 invasive cervical carcinoma (ICC) cases, 150 of whom had squamous cell carcinoma (SCC), and 527 controls were identified. Antibodies to HPV16 and HPV18 E6 and E7 proteins were determined by tag enzyme-linked immunoassays.


RESULTS
HPV16/18 E6 and E7 antibodies were detected infrequently (7.0%) in women in whom SCC later developed and yielded a moderately increased estimate of associated relative risk (odds ratio 2.7, 95% CI 1.1-6.4). Sensitivity of the combined antibody tests for the detection of occult SCC varied between 6% and 14% but was not related to time lag between serum sampling and cancer diagnosis.


CONCLUSIONS
HPV16/18 E6 and E7 antibody responses are not sensitive markers of occult cervical cancer.
Lehtinen
Matti
M
Department of Infectious Disease Epidemiology and Microbiology, National Public Health Institute, Helsinki, Finland. llmale@uta.fi
Pawlita
Michael
M
Zumbach
Klaus
K
Lie
Katherine
K
Hakama
Matti
M
Jellum
Egil
E
Koskela
Pentti
P
Luostarinen
Tapio
T
Paavonen
Jorma
J
Pukkala
Eero
E
Sigstad
Eva
E
Thoresen
Steinar
S
Dillner
Joakim
J
D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins; D005260:Female; D005387:Finland; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009664:Norway; D009856:Oncogene Proteins, Viral / Q000276:immunology; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D013548:Sweden; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000821:virology*
D000914:Antibodies, Viral; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16