Prediction of recurrence after treatment for high-grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisation.
OBJECTIVE
The aim of this study was to examine the accuracy of the presence of high-risk human papillomavirus (HR-HPV) DNA (HR-HPV DNA test) postconisation as prediction of recurrent or residual cervical intraepithelial neoplasia (CIN) after treatment of high-grade cervical intraepithelial lesions (CIN2+) in a prospective study and to compare this with follow-up cytology and the marginal status of the excised tissue.


METHODS
Prospective follow-up study.


METHODS
Unselected women presenting at colposcopy clinic of University Hospital Gasthuisberg, Leuven.


METHODS
Seventy-two women treated with conisation for CIN2 or CIN3.


METHODS
Women were followed by HR-HPV DNA test (Hybrid Capture II test of Digene) every 3 to 6 months. The same vial was used for cytology and the HR-HPV DNA test (SurePath). All women were further followed by colposcopy and cytology for 24 months at 6-month intervals. The outcome of the study was presence of >CIN2, proven with colposcopy-directed biopsy occurring within 24 months after treatment. HR-HPV status was correlated with recurrent or residual CIN2+.


METHODS
Sensitivity, specificity, predictive values and diagnostic odds ratios to predict treatment failure or cure were computed for HR-HPV testing, marginal status and follow-up cytology. HR-HPV status was also correlated with section margins postconisation and with the first cervical smear.


RESULTS
In 6 of the 72 treated women (8%), residual or recurrent CIN occurred. Women with recurrence were significantly older than women without a recurrence (51.5 +/- 9.6 versus 39.8 +/- 12.2 years, P= 0.007). All six women with recurrence were HR-HPV positive, four had a positive follow-up smear (>or=atypical squamous cells of uncertain significance = ASCUS+) and only two had involved section margins. Among the 66 cured women, 15 were HR-HPV positive, 6 had an abnormal smear and 12 had positive section margins. Sensitivity of cytology, positive section margins and HR-HPV DNA positivity was 66.7, 33.3 and 100% to predict treatment failure. Specificity of the three tests was, respectively, 90.9, 81.8 and 77.3%. Women with HR-HPV DNA at 3 to 6 months showed recurrent or residual CIN in 15% (2/13) if they had normal follow-up Pap smears and in 50% (4/8) if they had abnormal Pap smears. Margin status was not statistically significantly associated with human papillomavirus status.


CONCLUSIONS
Persistence or clearance of HR-HPV DNA is an early valid prognostic marker of failure or cure after treatment for CIN2+ and is more accurate than cytology or section margin status at the time of conisation. The absence of HR-HPV DNA has a 100% negative predictive value. Higher age at conisation may be a previously unrecognised risk factor for recurrence.
Verguts
J
J
Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Catholic University Leuven, Leuven, Belgium. jasper.verguts@uz.kuleuven.ac.be
Bronselaer
B
B
Donders
G
G
Arbyn
M
M
Van Eldere
J
J
Drijkoningen
M
M
Poppe
W
W
D000328:Adult; D001707:Biopsy, Needle / Q000592:standards; D002584:Cervix Uteri / Q000473:pathology; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000821:virology*; D018365:Neoplasm, Residual; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000821:virology*
D004279:DNA, Viral