National experience in the first two years of primary human papillomavirus (HPV) cervical screening in an HPV vaccinated population in Australia: observational study

Abstract

Objective: To review the first two years of the primary human papillomavirus (HPV) cervical screening programme in an HPV vaccinated population.

Design: Observational study.

Setting: Australia.

Participants: 3 745 318 women with a primary HPV test between 1 December 2017 and 31 December 2019; most women aged <40 years had previously been offered vaccination against HPV16 and HPV18.

Interventions: Primary HPV screening with referral if HPV16 or HPV18 (HPV16/18) positive and triage with liquid based cytology testing (threshold atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion) for women who were positive for high risk HPV types other than 16/18. A 12 month follow-up HPV test was recommended in triaged women with a negative or low grade cytology result, with referral if they tested positive for any high risk HPV type at follow-up.

Main outcome measures: Proportion of women who had attended for their first HPV screening test, tested positive, and were referred for colposcopy; and short term risk of detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse, CIN grade 3 or worse, or cancer.

Results: 54.6% (n=3 507 281) of an estimated 6 428 677 eligible women aged 25-69 had undergone their first HPV test by the end of 2019. Among those attending for routine screening, positivity for HPV16/18 and for HPV types not 16/18 was, respectively, 2.0% and 6.6% in women aged 25-69 (n=3 045 844) and 2.2% and 13.3% in highly vaccinated cohorts of women aged 25-34 (n=768 362). Colposcopy referral (ages 25-69 years) was 3.5%, increasing to an estimated 6.2% after accounting for women who had not yet had a 12 month repeat test. Cervical cancer was detected in 0.98% (456/46 330) of women positive for HPV16/18 at baseline, including 0.32% (89/28 003) of women with HPV16/18 and negative cytology. Women with HPV types not 16/18 and negative or low grade cytology at both baseline and 12 months were at low risk of serious disease (3.4% CIN grade 3 or worse; 0.02% cancer; n=20 019) but estimated to account for 62.0% of referrals for this screening algorithm.

Conclusions: Colposcopy referral thresholds need to consider underlying cancer risk; on this basis, women with HPV16/18 in the first round of HPV screening were found to be at higher risk regardless of cytology result, even in a previously well screened population. Women with HPV types not 16/18 and negative or low grade cytology showed a low risk of serious abnormalities but constitute most referrals and could be managed safely with two rounds of repeat HPV testing rather than one. HPV16/18 driven referrals were low in HPV vaccinated cohorts.

Fig 1

Cohort description (results and management for women aged 25-69). Low grade=cytology results of atypical squamous cells of undetermined significance or low grade squamous intraepithelial lesion. High grade=cytology results of atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion, high grade intraepithelial lesion, or more severe abnormality or any glandular abnormality. Non-screening reasons include investigation of signs and symptoms or follow-up after a previous abnormality (including test of cure after treatment). Follow-up not completed = women who had not yet attended for their 12 month follow-up test (including that 12 months had not yet elapsed), or were followed up outside guidelines. Assessable=women with a record that colposcopy occurred after the referring human papillomavirus (HPV) test but excluding women with an indication that histology was collected but the histology result was not available. Women with HPV16/18 detected and unsatisfactory liquid based cytology result are classified as higher risk and recommended to have a sample for liquid based cytology collected at colposcopy. Risk level cannot be determined for women with HPV types not 16/18 detected and unsatisfactory liquid based cytology result; guidelines recommend that these women reattend for a repeat liquid based cytology test in six weeks. In the current analysis, women with HPV types not 16/18 detected are only categorised as having an unsatisfactory liquid based cytology result if no subsequent satisfactory result was available on the National Cervical Screening Register and had occurred by 31 December 2019 (restricted to tests where the reason was reflex liquid based cytology after detection of oncogenic HPV in primary screening)

Fig 2

Proportion of women classified as higher risk (colposcopy referral recommended), with and without scaling to account for women who had not yet had their 12 month repeat test, by age group and reason for referral. Solid bars represent referrals observed so far; transparent bars and values in parentheses include scaling to account for women who had not yet had their 12 month repeat test. Results are restricted to women aged 25-69, as different management is recommended for women aged 70-74 undergoing exit testing. HPV16/18+=positive for human papillomavirus (HPV) types 16/18 at baseline screening test. Triage+=positive for HPV types not 16/18 with atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H) or worse or glandular abnormalities on liquid based cytology. 12 month follow-up (HPV16/18+ or HPV types not 16/18 and ASC-H+)=12 month test result is HPV positive, and either positive for HPV16/18, or liquid based cytology result is ASC-H or worse or any glandular abnormality, or both. 12 month follow-up (HPV types not 16/18 and ≤LSIL (low grade squamous intraepithelial lesion))=12 month test result is HPV types not 16/18 positive and liquid based cytology result is negative or ASC-US (atypical squamous cells of undetermined significance) or LSIL. ASC-H+=ASC-H, high grade squamous intraepithelial lesion, or more severe abnormality or any glandular abnormality, or both. See supplementary tables A10 and A11 for data supporting this figure

Fig 3

Risk of detecting histological cervical intraepithelial neoplasia (CIN) grade 2 or worse, CIN grade 3 or worse, cancer, and frankly invasive cancer among women attending for colposcopy, by reason for referral and age group. Results are restricted to women aged 25-69, as different management is recommended for women aged 70-74 undergoing exit testing. HPV16/18+=positive for human papillomavirus (HPV) types 16/18 at baseline screening test. Triage+=positive for HPV types not 16/18 with atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H) or worse or glandular liquid based cytology result. 12 month follow-up (HPV16/18+ or HPV not 16/18 and ASC-H+)=12 month test result is HPV positive, and either positive for HPV16/18 or ASC-H or worse or glandular abnormality on liquid based cytology, or both. 12 month follow-up (HPV not 16/18 and ≤LSIL (low grade squamous intraepithelial lesion))=12 month test result is HPV types not 16/18 positive and liquid based cytology result is negative or ASC-US (atypical squamous cells of undetermined significance) or LSIL. ASC-H+=liquid based cytology result of ASC-H, high grade squamous intraepithelial lesion or more severe abnormality or any glandular abnormality. See supplementary tables A17 and A18 for data supporting this figure

Fig 4

Pre-test and post-test probability (%) of cervical intraepithelial neoplasia grade 3 or worse, cancer, and frankly invasive cancer. Results are for women of all ages. High grade+=atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H), high grade squamous intraepithelial lesion (HSIL), or more severe abnormality or any glandular abnormality. Low grade=atypical squamous cells of undetermined significance (ASC-US) or low grade squamous intraepithelial lesion (LSIL); LBC=liquid based cytology. See supplementary tables A20-A22 for data supporting this figure