The impact of age and high‐risk human papillomavirus (hrHPV) status on the prevalence of high‐grade cervical intraepithelial neoplasia (CIN2+) in women with persistent hrHPV‐positive, cytology‐negative screening samples: a prospective cohort study

Abstract

Objective To establish the prevalence of high‐grade cervical intraepithelial neoplasia (CIN2+) in women referred to colposcopy with persistent high‐risk human papillomavirus (hrHPV) cytology‐negative screening sample according to hrHPV genotype, age at referral and colposcopic performance. Design Prospective cohort study. Setting Single colposcopy clinic linked to a population‐based screening programme. Population Women referred with persistent hrHPV cytology‐negative routine screening samples. Methods Prospective study with descriptive statistics from a single colposcopy unit between June 2014 and July 2019. Main outcome measures Prevalence of hrHPV genotypes and CIN2+, positive predictive value for colposcopic impression, and inadequate colposcopic examinations. Results A total of 3107 women were referred. Prevalence of CIN2+ was highest for persistent HPV16 infections (10.7%) compared with HPV18 (3.6%) or HPVO (4.7%). Prevalence of CIN2+ declined with age (25–34 years 14.2% to 55–64 years 1.1%) whereas the percentage of women with an inadequate colposcopic examination increased (25–34 years 0.9% to 55–64 years 29.5%). High‐grade colposcopic impression fell over time during the study from 16.1 to 5.1%. The positive predictive value for colposcopic impression of CIN2+ was affected by hrHPV genotype (57.3% for HPV16 versus 32.1% for nonHPV16). The adjunctive use of electrical impedance spectroscopy detected an extra 42 cases of CIN2+, which was irrespective of hrHPV genotype. Conclusions Primary hrHPV cervical screening increases detection of CIN2+; however, low specificity results in more women being referred to colposcopy with a low prevalence of CIN2+. Colposcopy performs poorly in some groups, particularly with HPVO infections and women over 50 years of age. An appropriate threshold for referral to colposcopy in primary hrHPV screening has not been established. Tweetable abstract Low prevalence of CIN2+ in HPV‐positive negative cytology samples. HPV genotype, age and prevalence of CIN2+ affect colposcopic performance.

Prognostic value of Electrical Impedance Spectroscopy (EIS) when used as an adjunct to Colposcopy – a longitudinal study

“…This was a service evaluation carried out in the Jessop Wing Colposcopy clinic and so no ethical approval was required [ 6 ]. All patient data was anonymised.…”

Genotype-specific Distribution and Change of High-risk Human Papillomavirus Infection and the Association with Cervical Progression Risk in Women with Normal Pathology and Abnormal Cytology in a Population-based Cohort Study in China

“…Oral contraceptive use has been reported to increase the risk of developing cervical cancer in women with normal cytology in a retrospective population-based cohort study [30]. Recently, a UK prospective cohort study found that the progression probability of normal cervical cytology to CIN2+ decreased with age, with the highest in the 25-34 years old population [31].…”

Cervical cancer prevention among older women – challenges in screening, diagnostic workup and treatment

“…5 As several studies have demonstrated that HPV-based screening is associated with a significantly higher sensitivity for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) detection compared with screening with cytology, many European countries have either switched to or plan to implement HPV-based screening. 12,14 However, the sensitivity of HPVbased screening has also been reported to decline with age. 12 Whether this is explained by sampling issues or because older women are more likely to be diagnosed with an HPV-negative cancer 15 compared with younger women remains unclear.…”

“…A previous US study reported that 19% of cervical cancer cases were HPV negative and 5.5% were cotest negative (ie cytology and HPV), with older women more likely to test HPV-negative as compared with younger women. 16 As most newly detected HPV infections are transient and are associated with a low risk of CIN2+, 12,14 it is important to apply a triage strategy to identify women at increased risk who area in need of referral to colposcopy, thereby reducing the number of unnecessary colposcopies. Triage of HPV-positive women is typically performed with cytology and/or partial or complete HPV genotyping; however, given the low sensitivity of cytology in older women and the low proportion of HPV16/18-positive cancers among older women, 17 triage by cytology and partial genotyping may not be the best strategies in older women.…”

“…The risk of inadequate colposcopy increases with age, with up to 67% of women aged 61.5 years having an inadequate colposcopy. 11,14 To improve the performance of colposcopy (ie transition from not visible to visible squamocolumnar junction), pre-colposcopic medical treatment with estrogen (vaginal or oral) or misoprostol has been suggested. 11,20 Unfortunately, previous studies suffer from a small sample size, have different inclusion criteria (ie postmenopausal bleeding, abnormal cytology, vaginal discharge or suspicious cervix on speculum examination) and are not conducted within an organized screening program.…”