Long-term HPV type-specific risks for ASCUS and LSIL: A 14-year follow-up of a randomized primary HPV screening trial

Abstract

Human papillomavirus (HPV) infections result in a significant burden of low-grade cervical lesions. Between 1997 and 2000, our randomized trial of primary HPV screening enrolled 12,527 women participating in population-based screening. Women between 32 and 38 years of age (median: 34, interquartile range: 33-37) were randomized to HPV and cytology double testing (intervention arm, n 5 6,257 enrolled, n 5 5,888 followed-up) or to cytology, with samples frozen for future HPV testing (control arm, n 5 6,270 enrolled, n 5 5,795 followed-up). We estimated the HPV type-specific, long-term absolute risks (AR), and population attributable proportions (PAR) for cytological diagnoses of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) and for histopathologically diagnosed cervical intraepithelial neoplasia grade 1 (CIN1). The women were followed using comprehensive, nationwide register-based follow-up. During a mean follow-up time of 11.07 years, 886 ASCUS and LSIL lesions were detected, 448 in the intervention arm and 438 in the control arm. Poisson regression estimated the incidence rate ratios (IRRs) of low-grade lesions by HPV type. The IRRs were strongly dependent on follow-up time. The IRRs for ASCUS/LSIL associated with high-risk HPV positivity were 18.6 (95% CI: 14.9-23.4) during the first screening round, 4.1 (95% CI: 2.8-6.2) during the second, 2.6 (95% CI: 1.7-4.1) during the third, and 1.1 (95% CI: 0.7-1.8) for >9 years of follow-up, with similar declines seen for the individual types. Type 16 contributed consistently to the greatest proportion of ASCUS, LSIL, and CIN1 risk in the population (first screening round PAR: ASCUS: 15.5% (95% CI: 9.7-21.9), LSIL: 14.7% (95% CI: 8.0-20.9), and CIN1: 13.4% (95% CI: 3.2-22.5)), followed by type 31 [8.4% (95% CI: 4.2-12.5) for ASCUS to 17.3% (95% CI: 6.8-26.6) for CIN1]. In summary, most ASCUS/LSIL lesions associated with HPV infection are caused by new HPV infections and most lesions are found during the first screening round.Quantifying the risks for cervical precancerous lesions associated with different human papillomavirus (HPV) types has been an area of intense investigation. HPV type distribution differs greatly by grade of the lesion, with a greater diversity of types found in low-grade lesions and a dominance of HPV 16 and 18 in high-grade lesions.1,2 Considerable resources are used in the follow-up and referral of women with low-grade lesions and a range of triage tests and management algorithms have been proposed for these lesions. 3,4 In Sweden, ASCUS and LSIL lesions were found in approximately 6% of cervical samples taken in 2012, triggering triage with HPV and subsequent follow-up testing, depending on HPV status. 5HPV testing is increasingly used in triaging low-grade lesions and therefore studies have recently focused on quantifying Key words: ASCUS, LSIL, HPV infections, HPV testing, cervical cancer screening Abbreviations: AR: absolute cumulative risk; ASCUS: atypical squamous cells of un...

High-risk human papillomavirus genotype distribution and attribution to cervical cancer and precancerous lesions in a rural Chinese population

“…These results are consistent with those of Lu et al in Beijing [28] and the study on Chinese women in 2013 which showed that 71.4% of HR-HPV positive CIN2+ cases were attributable to HPV16 or 18 [29]. A 14-year follow-up study in Sweden presented HPV16 and 31 as contributing to higher incidences of CIN2+ [1130]. …”

Human papillomavirus types in cervical dysplasia among young HPV‐vaccinated women: Population‐based nested case–control study

“…In contrast, nonvaccine HPV types HPV 33, 51, 52, 56, 59 and 66 were more common in our study than in the prevaccination cohort . HPV 31, 35 and 45 were more prevalent in CIN2‐3 cases, while HPV 39, 42, 68 and 90 were more common only among CIN1 cases when compared to the prevaccination data (Table ) …”

“…We observed that the HPV DNA prevalence of vaccine‐targeted types was much lower than the population‐based prevalence of HPV DNA genotypes in Sweden during the prevaccination era (Table ) . None of all tested samples ( n = 367) contained the vaccine types HPV 6 or 11 (data not shown).…”

Atypical Squamous Cells: Cytopathological Findings and Correlation with HPV Genotype and Histopathology

“…The frequency of this genotype distribution is quite similar to that found in another Cobas PCR study for ASC-US [38]. According to some authors, a predominance of HPV-16 and -18 genotypes does not necessarily occur in ASC-US, and subtype variability is expected [39]. …”