Clinical implications of transitioning from cytology to human papillomavirus‐based cervical cancer screening

Cervical cancer remains the fourth most common among women worldwide, accounting for more than 500 000 new cases annually. can be effectively prevented through screening, which allows detection and treatment of precursor lesions, thereby preventing their progression to cancer. Following introduction Papanicolaou smear cytology-based screening (and later liquid-based cytology [LBC]), cervical incidence mortality declined dramatically, several studies have demonstrated that regular is associated with an 80%-90% reduced risk death from disease.1 Acknowledging central role human papillomavirus (HPV) in natural history cancer, many well-established programs high-income countries are transitioning morphology-based LBC molecular HPV-based screening. Large randomized controlled trials observational significantly sensitive detecting intraepithelial neoplasia grade 2 or worse (CIN2+) CIN3+ compared cytology.2 A single HPV-negative test provides greater reassurance against CIN2+ a normal LBC, safely enabling longer intervals between tests.2 Furthermore, superior glandular lesions (ie, adenocarcinoma situ) older women. Taken together, these findings suggest has potential prevent cancers deaths disease However, downside its low specificity detection, resulting higher number false-positive screens screening.2 The underlying reason lower HPV infections only transiently detected short-duration detections 5- 10-year CIN2+. To improve reduce unnecessary colposcopies, different triage strategies been explored. One commonly used cytology, atypical squamous cells undetermined significance being typical threshold referral. Other include use partial complete genotyping samples, as significant difference across genotypes, type 16 highest CIN2+.3 Depending on selection test, further risk-stratification by genotype may possible. This clinical value because some non-HPV-16/18 types, such HPV-31 HPV-33, others HPV-66 HPV-52). Choosing strategy challenging depends factors. Ideally, you would want cheap, high reproducibility, increases without compromising sensitivity. practice substantial improvement almost always comes at cost overall As result, balance sensitivity/specificity trade-off when choosing strategy, recommending referral worse. There no universally “correct” choice; appropriate made based tolerance missing resource availability each setting health system. maximizes sensitivity will miss fewer cases, but increase colposcopy management burden. Alternatively, maximize burden clinics increased surveillance test-positive/disease-negative expense disease. guides age ranges recommended testing routine (30-65 years). typically not under 30 years, within first years after sexual debut mostly transient very progressing invasive next 5-10 years. Screening starting ages 21-25 using standard methods. during midlife likely detect persistent uncontrolled infections, neoplasia. counseling positive HPV, it important emphasize just “trigger” need rule out detailed colposcopic examination. In fact, (like ASC-US low-grade intra-epithelial lesion CIN1 histology) result diagnosis return 1-2 persists should carefully evaluated, particularly if occurring postmenopausal where epithelium often atrophic transformation zone retracted into canal. women, low, suggesting better identify greatest disease, including diagnostic cone biopsy case infection lasting ≥2 Given decline HPV-16-positive HPV-18-positive increasing age,4 performing stratification caution non-HPV-16 HPV-18 high-risk infection. Finally, clinicians prepared changes prevalence utilization switch once every 3 5 For example, sensitivity, missed attending (if selected). supported reporting following round upon implementation primary screening.5, 6 also expected referral, subsequent treatment, intensive follow-up gynecology departments anticipate prepare referrals, fluctuate time initial decade program change.7 rounds, rates referrals groups levels out. aware differs duration infection, risks prevalent versus newly entering record previous results, impossible determine whether detected. analysis 15 experience USA suggests HPV-positive information status (first ever test) documented “prevalent persistent” screen.5 summary, less specific cytology. Therefore, needed separate those who undergo repeat testing. Selecting specificity. Upon implementation, might temporarily. authors thank Professor Berit Andersen, Department Public Health Programs, Randers Regional Hospital, Denmark, commenting Editorial.