The following is a summary of “Risk stratification of HPV-positive results using extended genotyping and cytology: Data from the baseline phase of the Onclarity trial,” published in the July 2023 issue of Gynecologic Oncology by Stoler et al.
Optimizing the balance between colposcopy referrals and detecting high-grade cervical intraepithelial neoplasia (CIN) during cervical cancer screening necessitates robust triage strategies. The researchers compared the efficacy of extended HPV genotyping (xGT) with cytology triage to previously published data for high-grade CIN detection by HPV16/18 primary screening in conjunction with p16/Ki-67 dual staining (DS). The baseline phase of the Onclarity trial enrolled 33,858 participants, of whom 2,978 were HPV-positive. Risk values for ≥CIN3 were calculated for Onclarity result groupings corresponding to HPV16, not HPV16 but HPV18 or 31, not HPV16/18/31 but HPV33/58 or 52, and not HPV16/18/31/33/58/52 but HPV35/39/68 or 45 or 51 or 56/59/66 across all cytology categories.
During ROC analyses, published data from the IMPACT trial for HPV16/18 plus DS served as a comparison. There were 163 cases of CIN3 detected. The ≥CIN3 risk stratum hierarchy (% risk of ≥CIN3) that resulted from this analysis included: >LSIL (39.4%); HPV16, ≤LSIL (13.3%); HPV18/31, ≤LSIL (5.9%); HPV33/58/52/45, ASC-US/LSIL (2.4%); HPV33/58/52, NILM (2.1%); HPV35/39/68/51/56/59/66, ASC-US/LSIL (0.9%); and HPV45/35/39/68/51/56/59/66, NILM (0.6%). For CIN3 ROC analysis, the optimal cutoff for sensitivity versus specificity was roughly between not HPV16 but HPV18 or 31, any cytology (≥CIN3 sensitivity = 85.9% and colposcopy-to- CIN3 = 7.4) and not HPV16/18/31 but HPV33/58/52, NILM (CIN3 sensitivity = 94.5% and colposcopy-to- ≥CIN3 = 10.8).
With DS triage, HPV16/18 demonstrated a sensitivity of 94.3% and a colposcopy-to- ≥CIN3 ratio of 11.4. To detect high-grade CIN, xGT and HPV primary screening plus DS were performed similarly. xGT provides results that stratify risk flexibly and dependably for colposcopy risk thresholds established by various organizations or guidelines.