Real-world data on cervical cancer risk stratification by cytology and HPV genotype to inform the management of HPV-positive women in routine cervical screening

Abstract

BACKGROUND: HPV16/18 detection may improve cervical cancer risk stratification and better guide which HPV-positive women warrant immediate colposcopy/biopsy. We estimated risks of cervical precancer and cancer by HPV genotype and cytology during the implementation phase of primary HPV testing in Norway. METHODS: A total of 3111 women, aged 34-69 years, testing HPV-positive at baseline and undergoing cytology testing from February 2015 to April 2018 had data available for analysis. Risk estimates with 95% confidence intervals (95%CIs) of cervical intraepithelial neoplasia grade 3 or more severe (CIN3+) were estimated for cytology results and HPV genotypes (HPV16, HPV18, and other high-risk HPV). RESULTS: CIN3+ risks were higher for HPV16/18 than other high-risk HPV genotypes. Among women with any cytologic abnormality [atypical squamous cells of undetermined significance or worse], immediate risks were 57.8% (95%CI = 53.0-62.6%) for HPV16, 40.2% (95%CI = 32.3-49.2%) for HPV18, and 31.4% (95%CI = 28.7-34.3%) for other high-risk HPV. Among those with normal cytology, CIN3+ risks were 19.9% (95%CI = 15.0-26.1%) for HPV16 positives, 10.8% (95%CI = 5.6-20.5%) for HPV18 positives, and 5.5% (95%CI = 4.2-7.1%) for other high-risk HPV. CONCLUSIONS: The benefits and harms of managing women based on HPV positivity and cytology results can be better balanced by inclusion of HPV genotyping in screening and choosing more conservative management for other high-risk HPV compared to HPV16/18.

<p>The Triage Effectiveness of an Extended High-Risk Human Papillomavirus Genotyping Assay for Women with Cytology Showing Atypical Squamous Cells of Undetermined Significance in China</p>

“…Although one study reported that the prevalence rate of HR-HPV among women with ASC-US was 41.7%, 23 another study reported a prevalence rate of 23%. 24 The prevalence rate of HR-HPV among patients with ASC-US was 47.6% in our research. Moreover, among patients with ASC-US whose biopsies proved to be CIN2+, the infection rates of HPV16, HPV18, HPV31, HPV33, HPV52 and HPV58 were 47.9%, 7.0%, 5.4%, 5.8%, 18.6% and 21.1%, respectively.…”

Human papillomavirus genotype-specific risks for cervical intraepithelial lesions

“…Thus, the HPV types detected in screening considerably affect the harms and benefit balance of the entire program, an observation, which was supported by a recent study confirming clinical benefit of immediate colposcopy referral for all HPV16/18-positive women whereas women with other hrHPV infections are triaged with cytology in a pre-vaccinated population. 41 One should notice that in Asian countries, for example, HPV58 has been reported to have a far more oncogenic profile compared with the Nordic countries, 42,43 implying that regional/ geographical differences should be considered in establishing an optimal screening program. Now, the optimal screening scenario should be considered for the scenario when all 2 v and 4 v HPV vaccine-targeted HPV types are eliminated, with an assumed prevalence of carcinogenic HPVs reduced to 28% among those who enter the screening program.…”

Reducing unnecessary referrals for colposcopy in hrHPV-positive women within the Dutch cervical cancer screening programme: A modelling study

“…The same conclusion was reached by a recent data study on the implementation phase of the hrHPV-based screening programme in Norway, where CIN3+ risk was estimated for cytology results and HPV genotypes. By inviting women with HPV-OHR and low-grade cytology for a repeat test instead of referring these women for colposcopy, the harms and benefits of the screening programme were found to be more balanced [27].…”