A study of HPV typing for the management of HPV-positive ASC-US cervical cytologic results

Abstract

Background In US cervical screening, immediate colposcopy is recommended for women with HPV-positive ASC-US (equivocal) cytology. We evaluated whether partial typing by Onclarity™ (BD) might identify HPV-positive women with low enough CIN3+ risk to permit 1-year follow-up instead. Methods The NCI-Kaiser Permanente Northern California Persistence and Progression Cohort includes a subset of 13,890 women aged 21+ with HC2 (Qiagen)-positive ASC-US at enrollment; current median follow-up is 3.0 years. Using stratified random sampling, we typed 2,079 archived enrollment specimens including 329 women subsequently diagnosed with CIN3+, 563 with CIN2, and 1,187 with <CIN2. Adjusting for sampling, we computed 3-year cumulative CIN3+ risks for each Onclarity typing channel, using Kaplan-Meier methods. Results The 3-year CIN3+ risk for all HC2-positive women with ASC-US was 5.2%; this establishes the “benchmark” risk for colposcopic referral. Hierarchically, 3-year cumulative risks for each typing channel were 16.0% for HPV16, 7.4% for HPV18, 7.0% for HPV31, 7.1% for grouped HPV33/58, 4.4% for HPV52, 3.9% for HPV45, 2.7% for HPV51, 1.6% for HPV39/68/35, and 1.3% for HPV59/56/66. Discussion ASC-US linked to HPV16, HPV18, HPV31, or HPV33/58 warrants immediate colposcopy. Optimal management of women with HPV52 or HPV45 is uncertain. Risk of women with only HPV51, HPV39/68/35, or HPV59/56/66 might be low enough to recommend 1-year retesting permitting viral clearance. This strategy would defer colposcopy for 40% of women with HPV-positive ASC-US, half of whom would be cotest-negative at 1-year return. Approximately 10% of those with CIN3 diagnosable at enrollment would be delayed 1 year instead. Cost-effectiveness analyses are needed.

Assessment of a New Lower-Cost Real-Time PCR Assay for Detection of High-Risk Human Papillomavirus: Useful for Cervical Screening in Limited-Resource Settings?

“…The biorepository is the basis of the Persistence and Progression (PaP) cohort study, an ongoing study of approximately 55,000 women who obtained cervical screening at KPNC. KPNC introduced cytology (Pap smear) and HPV cotesting with Hybrid Capture 2 (HC2; Qiagen, Germantown, MD) at 3-year intervals in 2003 (10). The PaP study, starting in 2007, stored residual exfoliative cervical specimens remaining from HC2 testing until 2011 (11).…”

“…The Onclarity assay (BD) is a multiplex qPCR assay that targets HPV type-specific E6 or E7 sequences (10). The assay provides genotyping information for 14 HPV types and utilizes 9 channels for (i) types 16, 18, 31, 45, 51, and 52 (separately), (ii) types 33 and 58 (HPV33/58) (pooled), (iii) types 35 and 68 (HPV35/68) (pooled), and (iv) types 56, 59, and 66 (HPV56/59/66) (pooled).…”

“…Until 2009, KPNC used conventional Pap smears and slides were reviewed manually with assistance from the BD FocalPoint slide profiler (BD Diagnostics, Burlington, NC) (10,11). Since 2009, KPNC has replaced conventional Pap smears with liquid-based cytology (SurePath; BD Diagnostics, Sparks, MD).…”

“…Women in the KPNC PaP cohort were referred to colposcopy and biopsy if indicated, based on HC2 and cytology cotesting results according to standard clinical practice (10). The worst histology results observed during follow up post-specimen collection for each woman were considered in the analysis.…”

Atypical Squamous Cells: Cytopathological Findings and Correlation with HPV Genotype and Histopathology

“…1) and ASC-H (Fig. 2) are not evolution stages of a true disease, but the result of an imprecise and temporary assessment of the current diagnosis [5]. These abnormalities represent the limitation of cytology as a screening method, which creates doubts in its management.…”