The effectiveness of human papillomavirus load, reflected by cycle threshold values, for the triage of HPV-positive self-samples in cervical cancer screening.

OBJECTIVE

The performance of Cobas4800 cycle threshold value (Ct-value, reflecting viral load) combined with human papillomavirus (HPV) 16/18 genotyping was explored as a method of risk stratification to triage patients after primary HPV screening of self-collected samples.

METHODS

The Chinese Multi-site Screening Trial database was reviewed, with focus on self-collected samples, using the results of Cobas4800 HPV assay. Quartiles of Ct-values of each genotype were used for grouping and developing screening algorithms. Diagnostic accuracy for paired comparisons between algorithms was obtained using McNemar's test.

RESULTS

A total of 10,498 women were included. The Ct-values of HPV16 and other high-risk HPV were inversely correlated with the severity of cervical lesions ( < 0.001). Risks for cervical intraepithelial neoplasia (CIN2+/CIN3+) were significantly stratified by Ct-values from channels detecting HPV16 and other high-risk HPV types. "HPV with HPV16/18 and reflex Ct <33.7" (algorithm G) achieved a favorable sensitivity to "HPV with atypical squamous cells of undetermined significance or worse (≥ASCUS)" (81.9% vs. 70.1% for CIN2+,  < 0.001), a comparable sensitivity to "HPV with HPV16/18 reflex cytology ≥ASCUS" (81.9% vs. 81.3% for CIN2+,  > 0.05), and resulted in a slightly lower specificity than the latter two algorithms (92.6% vs. 97.4% and 95.4% respectively for CIN2+,  < 0.05). However, algorithm G achieved a comparable sensitivity to HPV testing alone for CIN3+, and reduced the colposcopy referral rate from 13.7% for HPV testing alone to 8.4%.

CONCLUSIONS

HPV viral loads reflected by Ct-values are associated with the severity of cervical lesions. Ct-values with an appropriate cut-off of 33.7, combined with HPV16/18 genotyping, represent a promising triage of HPV-positive women particularly for self-collected samples.