Abstract
ObjectiveContinuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV) types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic) in predicting future development of high-grade cervical intraepithelial neoplasia (CIN) among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous epithelial lesion (LSIL) cytology.MethodsArchived SurePath cervical samples of women ≥ 35 years of age with high-risk HPV DNA-positive ASCUS (n = 211) or LSIL, (n = 131) were tested for the presence of high-risk HPV E6/E7 mRNA using the APTIMA HPV assay, and the women were monitored for development of histopathologically verified CIN2+.ResultsTwenty-nine percent (61/211) of the women in the ASCUS group, and 34.3% (45/131) in the LSIL group developed CIN2+ within 4.5 years of follow-up. The prevalence of HPV mRNA was 90.0% (95% CI 85.9-94.0) among women with ASCUS and 95.4% (95% CI 91.8-99.0) among women with LSIL. The presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among women with ASCUS and LSIL (p=0.02). The mRNA assay demonstrated high sensitivity in predicting future CIN2+ and CIN3 for index ASCUS (96.7%; 95% CI 87.6-99.4 and 100%; 95% CI 82.2-100, respectively) and LSIL (97.8%, 95% CI 86.8-99.9 and 100%, 95% CI 79.9-100, respectively). The corresponding specificity was low, 12.7% (95% CI 7.9-19.3) and 5.8% (95% CI 2.2-13.6), for future CIN2+, respectively. The negative predictive value of the HPV mRNA assay for detecting future CIN3 was 100%, since no mRNA-negative woman developed CIN3 (0/27) as compared to 13.6% (43/315) of the mRNA-positive women (p = 0.03).ConclusionThe APTIMA mRNA assay demonstrated high sensitivity but low specificity in predicting future CIN2+ among women with minor cytological abnormalities. The assay had high negative predictive value for future CIN3, indicating that HPV-mRNA-negative women are at low risk of progression to high grade CIN.
Highlights
Oncogenic human papillomaviruses (HPVs) are the main cause of cervical cancer, being found in close to 100% of cervical tumors [1]
The presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous epithelial lesions (LSIL) (p=0.02)
The assay had high negative predictive value for future CIN3, indicating that HPV-mRNA-negative women are at low risk of progression to high grade cervical intraepithelial neoplasia (CIN)
Summary
Oncogenic human papillomaviruses (HPVs) are the main cause of cervical cancer, being found in close to 100% of cervical tumors [1]. A systematic review of 423 studies showed that HPV-DNA of 48 different HPV types of the alpha papillomavirus genus was present in 52.1% of ASCUS and 74.2% of LSIL lesions [2]. In southern Sweden, HPV reflex testing by the use of MGP-PCR and Luminex [6, 7] is used as triage for all women >35 years of age with ASCUS/LSIL cytology. Women with HR-HPV type (s) and ASCUS or LSIL are referred to colposcopy. Unnecessary colposcopies could be avoided if only those with relevant HPV infections, i.e. women with persistently active HPV infection, who are at risk of development of high-grade lesions, were referred. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay in predicting future development of high-grade cervical intraepithelial neoplasia among HR-HPV DNA-positive women with ASCUS or LSIL cytology
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