Research article

Evaluation of adjunctive HPV testing by Hybrid Capture II^® in women with minor cytological abnormalities for the diagnosis of CIN2/3 and cost comparison with colposcopy

Andrea Guyot¹ , Shakir Karim² , May S Kyi³ and John Fox⁴

¹  Department of Microbiology of West Middlesex University Hospital and Quest Diagnostics, Twickenham Rd, Isleworth W7 6AF, UK

²  Department of Pathology of West Middlesex University Hospital and Quest Diagnostics, Twickenham Rd, Isleworth W7 6AF, UK

³  Department of Microbiology of West Middlesex University Hospital and Quest Diagnostics, Twickenham Rd, Isleworth W7 6AF, UK

⁴  Department of Obstetrics and Gynaecology of West Middlesex University Hospital, Twickenham Rd, Isleworth W7 6AF, UK

author email corresponding author email

BMC Infectious Diseases 2003, 3:23doi:10.1186/1471-2334-3-23

Published:	25 September 2003

Abstract

Background

As a proportion of high grade cervical intraepithelial neoplasia (CIN2/3) are associated with equivocal cervical smears, which show borderline or mild dyskaryosis, follow up with repeat smears, colposcopy and biopsy is required. Since infection with oncogenic Human Papilloma Virus (HR HPV) has been found to be associated with the development of cervical cancer, HRHPV testing appears to be an alternative.

Objective

The present study assesses if HRHPV testing can predict CIN2/3 in women referred for mild dyskaryosis and borderline cytological changes in an health authority with a referral policy to colposcopy after one single mild dyskaryotic Pap smear.

Study design

The HPV DNA Hybrid Capture II (Digene/Abbott, Maidenhead) was evaluated on 110 consenting women with mild dyskaryosis and 23 women with persistent borderline changes, who were referred for colposcopy between May and November 2001. A cost comparison between two referral policies was performed.

Results

CIN2/3 was diagnosed histologically in 30 of 133 women (22%) with minor cytological abnormalities. As the Receiver Operator Characteristics plot suggested a cut-off of 3 pg/ml the HRHPV HCII was evaluated at 3 RLU (relative light units) and at the manufacturer's recommendation of 1 RLU. At both cut-offs sensitivity and negative predictive value were high at 97%. Specificity was low at 37% at a cut-off of 1 pg/ml and 46% at a cut-off of 3 RLU. To remain cost neutral in comparison to immediate colposcopy the costs for one HR HPV HC II must not exceed £34.37 per test at a cut off of 3 pg/ml.

Conclusion

The negative likelihood ratio (NLR) was of good diagnostic value with 0.089 at 1 RLU and 0.072 at 3 RLU, which reduces the post-test probability for CIN2/3 to 2% in this population. Women with minor cytological disorders can be excluded from colposcopy on a negative HR HPV result.

Specificity can be improved by restricting HR HPV testing to women with persistent borderline cytological changes or to women over 30 years.