Abstract
BackgroundHPV16/18 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.MethodsA 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).ResultsCIN3+ 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.ConclusionsThe 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.
Highlights
HPV16/18 detection may improve cervical cancer risk stratification and better guide which human papillomavirus (HPV)-positive women warrant immediate colposcopy/biopsy
Categorising HPV-positive women hierarchically based on genotype, 650 (20.8%) women were HPV16 positive, 221 (7.1%) were HPV18 positive, and 2148 (69.0%) were positive for other high-risk HPV; and 92 (3.0%) for whom no HPV genotype details were recorded; these were included in the overall HPV positive category
For combinations of HPV-genotype and cytology results using real-world screening data in Norway, women who tested positive for HPV16 and/or HPV18 genotype had a higher risk of CIN3+ and CIN2+ compared with women who tested positive for other highrisk
Summary
HPV16/18 detection may improve cervical cancer risk stratification and better guide which HPV-positive women warrant immediate colposcopy/biopsy. HPV screening leads to a greater reduction in the overall incidence of cervical cancer compared to conventional cytology-based screening and it is recommended to use HPV as a screening test for women over 30 years of age.[4,5] HPV testing is more sensitive than cervical cytology alone in detecting CIN2 or more severe diagnoses (CIN2+) and CIN3 or more severe diagnoses (CIN3+).[5,6,7,8] primary HPV screening detects transient HPV infections, which increases the number of positive screening results and potentially the number of colposcopies performed,[5,9] the latter depending on the criteria for referral to colposcopy. For HPV-positive women with cytology negative for intraepithelial lesion or malignancy (NILM) or low-grade cytology, over-referral to colposcopy can lead to a larger number of colposcopy/biopsy results negative for CIN2+.10 This presents a major challenge to the limited colposcopy capacity in most healthcare systems.[10,11] It is important to choose a colposcopy referral threshold based on the balance between benefits and harms
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