Audit of laboratory sensitivity of human papillomavirus and cytology testing in a cervical screening program

The globally recommended public health policy for cervical screening is primary human papillomavirus (HPV) screening with cytology triaging of positives. To ensure optimal quality of laboratory services we have conducted regular audits of cervical smears taken before cervical cancer or cancer in situ (CIN3+) within an HPV-based screening program. The central cervical screening laboratory of Stockholm, Sweden, identified cases of CIN3+ who had had a previous cervical screening test up to 3 years before and randomly selected 300 cervical liquid-based cytology (LBC) samples for auditing. HPV testing with Roche Cobas was performed either at screening or with biobanked samples. HPV negative samples and subsequent biopsies were retrieved and tested with modified general primer HPV PCR and, if still HPV-negative, the LBCs and biopsies were whole genome sequenced. The Cobas 4800 detected HPV in 1020/1052 (97.0%) LBC samples taken before CIN3+. Further analyses found HPV in 28 samples, with nine of those containing HPV types not targeted by the Cobas 4800 test. There were 4 specimens (4/1052, 0.4%) where no HPV was detected. By comparison, the proportion of CIN3+ cases that were positive in a previous cytology were 91.6%. We find that the routine HPV screening test had a sensitivity in the real-life screening program of 97.0%. Regular laboratory audits of cervical samples taken before CIN3+ can be readily performed within a real-life screening program and provide assurance that the laboratory of the real-life program has the expected performance.