Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease.
BACKGROUND
Loop electrosurgical excision procedure (LEEP) is the predominant treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN2+) in the United States, yet following treatment approximately 10% of women are diagnosed again with CIN2+, necessitating close follow-up of such patients.


METHODS
Surveillance strategies using cytology and/or human papillomavirus (HPV) testing were compared among women who underwent LEEP (n = 610) in the Atypical Squamous Cells of Undetermined Significance (ASCUS) Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. Cervical specimens, collected at 6-month visits for 2 years, were used for cytology, Hybrid Capture 2 (HC2) detection of carcinogenic HPVs, and PCR for genotyping of carcinogenic and noncarcinogenic HPV types. At exit, women had colposcopy for safety and disease ascertainment.


RESULTS
At the visit post-LEEP (median time: 4.5 months after LEEP), 36.9% [95% confidence interval (95% CI), 32.7-41.1%] of women were positive for carcinogenic HPV by PCR and 33.7% (95% CI, 29.7-37.9) had ASCUS or more severe (ASCUS+) cytology. The overall 2-year cumulative incidence of histologically confirmed posttreatment CIN2+ was 7.0%; this could be further stratified by the HPV risk category detected at the 6-month visit after LEEP. The 2-year risk associated with HPV16 positivity was 37.0%, significantly higher than for other carcinogenic HPV types (10.8%, P < 0.001), noncarcinogenic types (1.5%, P < 0.001), or testing HPV negative (0%). Post-LEEP cytology (using a positive threshold of ASCUS+) was 78.1% (95% CI, 60.0-90.7%) sensitive for detection of posttreatment CIN2+. By comparison, PCR for carcinogenic HPV and combination testing (using a positive result from carcinogenic HPV testing or cytology as the test threshold with HPV-negative ASCUS not referred) were significantly more sensitive (96.9% for each, P = 0.03); HC2 alone was nonsignificantly more sensitive (90.6%, P = 0.3). Specificity was similar for ASCUS+ cytology (69.1%, 95% CI, 64.6-73.3%) and PCR for carcinogenic HPV (67.1%, P = 0.5), yet was lower for HC2 (63.8%, P = 0.048) and combination testing (62.9%, P = 0.02).


CONCLUSIONS
Women who tested positive after LEEP for carcinogenic HPV types, especially HPV16, had high risk of subsequent CIN2+. HPV-based detection methods, alone or in combination with cytology, may be useful to incorporate in post-LEEP management strategies.
Kreimer
Aimée R
AR
National Cancer Institute, NIH, 6130 Executive Boulevard, Bethesda, MD 20892-7333, USA. kreimera@mail.nih.gov
Guido
Richard S
RS
Solomon
Diane
D
Schiffman
Mark
M
Wacholder
Sholom
S
Jeronimo
José
J
Wheeler
Cosette M
CM
Castle
Philip E
PE
D000328:Adult; D016009:Chi-Square Distribution; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D011230:Precancerous Conditions / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000601:surgery* / Q000821:virology*; D011237:Predictive Value of Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000601:surgery* / Q000821:virology*