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Triage of LSIL / ASC‐US with p16/Ki‐67 dual staining and human papillomavirus testing: a 2‐year prospective study
Author(s) -
White C.,
Bakhiet S.,
Bates M.,
Keegan H.,
Pilkington L.,
Ruttle C.,
Sharp L.,
O' Toole S.,
Fitzpatrick M.,
Flannelly G.,
O' Leary J. J.,
Martin C. M.
Publication year - 2016
Publication title -
cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.512
H-Index - 48
eISSN - 1365-2303
pISSN - 0956-5507
DOI - 10.1111/cyt.12317
Subject(s) - medicine , colposcopy , cervical intraepithelial neoplasia , cytology , ki 67 , population , gynecology , human papillomavirus , prospective cohort study , gastroenterology , cervical cancer , pathology , cancer , immunohistochemistry , environmental health
Objective To investigate human papillomavirus (HPV) DNA testing and p16/Ki‐67 staining for detecting cervical intraepithelial grade 2 or worse (CIN2+) and CIN 3 in women referred to colposcopy with minor abnormal cervical cytology low‐grade squamous intraepithelial lesions (LSIL) and atypical squamous cells of undermined significance (AS C‐US) . The clinical performance of both tests was evaluated as stand‐alone tests and combined, for detection CIN 2+ and CIN 3 over 2 years. Methods ThinPrep ® liquid‐based cytology ( LBC ) specimens were collected from 1349 women with repeat LSIL or ASC ‐ US . HPV DNA was performed using Hybrid Capture. Where adequate material remained ( n = 471), p16/Ki‐67 overexpression was assessed. Clinical performance for detection of histologically diagnosed CIN 2+ and CIN 3 was calculated. Results Approximately 62.2% of the population were positive for HPV DNA , and 30.4% were positive for p16/Ki‐67. p16/Ki‐67 showed no significant difference in positivity between LSIL and ASC ‐ US referrals (34.3% versus 28.6%; P = 0.189). Women under 30 years had a higher rate of p16/Ki‐67 compared to those over 30 years (36.0% versus 26.6%; P = 0.029). Overall HPV DNA testing produced a high sensitivity for detection of CIN 3 of 95.8% compared to 79.2% for p16/Ki‐67. In contrast, p16/Ki‐67 expression offered a higher specificity, 75.2% versus 40.4% for detection of CIN 3. Combining p16/Ki‐67 with HPV DNA improved the accuracy in distinguishing between CIN 3 and < CIN 3. The absolute risk of CIN 3 increased from 15.6% in women who were HPV DNA positive to 27% in women positive for HPV DNA and p16/Ki‐67. Those negative for HPV DNA and p16/Ki‐67 had a low risk of 1.2% of CIN 3. Conclusion The addition of p16/Ki‐67 to HPV DNA testing leads to a more accurate stratification of CIN in women presenting with minor cytological abnormalities.