A daunting challenge: Human Papillomavirus assays and cytology in primary cervical screening of women below age 30years

Abstract

We compared cytology with Hybrid Capture 2 (HC2), cobas, CLART and APTIMA Human Papillomavirus (HPV) assays in primary cervical screening at age 23-29 years based on data from the Danish Horizon study. SurePath samples were collected from 1278 women undergoing routine cytology-based screening. Abnormal cytology was managed according to the routine recommendations, and women with cytology-normal/HPV-positive samples were invited for repeated cytology and HPV testing in 1.5 years. Loss to follow-up was similar between HPV assays. ⩾ CIN3 was detected in 44 women. The sensitivity of HC2 for ⩾ CIN3 was 95% (95% confidence interval (CI): 85-99), of cobas 98% (95% CI: 88-100), of CLART 100% (95% CI: 92-100), of APTIMA 82% (95% CI: 67-92), and of cytology 59% (95% CI: 43-74). Specificity for ⩾ CIN3 varied between 61% (95% CI: 59-64) for cobas and 75% (95% CI: 73-78) for APTIMA, and was 94% (95% CI: 93-96) for cytology. Similar results were observed for ⩾ CIN2 (N = 68). HPV screening with cytological triage doubled the number of colposcopies compared to cytology screening, and increased the frequency of repeated testing by four (APTIMA) to seven (cobas) times. The positive predictive value of a referral for colposcopy was relatively high for all screening tests (⩾ 30% for ⩾ CIN3, and ⩾ 50% for ⩾ CIN2). CIN1 was detected by cytology in ∼ 1% of women, and in ∼ 2% by any of the four HPV assays. Although highly sensitive, HPV-based screening of young Danish women should be approached cautiously, as it resulted in large reductions in specificity, and increased the demand for additional testing.

HPV for cervical cancer screening (HPV FOCAL): Complete Round 1 results of a randomized trial comparing HPV‐based primary screening to liquid‐based cytology for cervical cancer

“…In most population‐based studies, HPV prevalence is highest in younger women (<35 years) and most of those are a result of transient HPV infections that will clear without leading to any cervical lesions of consequence . As such, there is uncertainty as to whether there is an advantage to offering HPV‐based screening to women in these younger cohorts, as screening may result in increased false positive screens and unnecessary procedures, including colposcopy and treatment.…”

“…This facilitated the identification of potentially transient HPV infections that did not result in dysplasia, with the intent of minimizing the number of unnecessary colposcopy procedures on women with HPV infections. 27 In most population-based studies, HPV prevalence is highest in younger women (<35 years) 28,29 and most of those are a result of transient HPV infections that will clear without leading to any cervical lesions of consequence. 30 As such, there is uncertainty as to whether there is an advantage to offering HPV-based screening to women in these younger cohorts, as screening may result in increased false positive screens and unnecessary procedures, including colposcopy and treatment.…”

Use of the Aptima mRNA high-risk human papillomavirus (HR-HPV) assay compared to a DNA HR-HPV assay in the English cervical screening programme: a decision tree model based economic evaluation

“…The positivity seen in the HORIZON trial was 20.2% and 12.3% when DNA and mRNA HPV tests were used respectively in women aged 23–65 years 32 33. The positivity seen in the English pilot screening programme, where women were screened between the ages of 25 and 64, was lower but still comparable at 12.7% (using a mix of DNA and mRNA tests, the breakdown is unknown) 20.…”

“…This included contacting the study authors to request the data required for the model if it was not published in the format required for the model. Four studies were found that contained head to head data comparing the mRNA to DNA HR-HPV test in a primary screening manner: CERVIVA from Ireland,31 German AHPV Screening Trial (GAST) from Germany,15 FOCAL from Canada,14 and HORIZON from Denmark 32 33. The CERVIVA trial is ongoing and has not yet published baseline data; hence was not considered further.…”

Referral population studies underestimate differences between human papillomavirus assays in primary cervical screening

“…We used data from the Horizon study, the design of which was described in detail previously . In short, we collected consecutive, routine, SurePath® samples from Department of Pathology of Copenhagen University Hospital Hvidovre in June‐August 2011.…”