新しい方法は子宮頸癌検診を改善する可能性がある(New method could improve cervical cancer screening)

2024-12-13 カロリンスカ研究所(KI)

<関連情報>

• https://news.ki.se/new-method-could-improve-cervical-cancer-screening
• https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004494

自己検体からのヒトパピローマウイルス遺伝子型と周期の閾値と高悪性度子宮頸部病変のリスク: 改良型ステップウェッジ実施可能性試験の事後分析 Human papillomavirus genotype and cycle threshold value from self-samples and risk of high-grade cervical lesions: A post hoc analysis of a modified stepped-wedge implementation feasibility trial

Jiayao Lei,Kate Cuschieri,Hasit Patel,Alexandra Lawrence,Katie Deats,YouScreen trial team ,Peter Sasieni ,Anita W. W. Lim
PLOS Medicine  Published: December 12, 2024
DOI:https://doi.org/10.1371/journal.pmed.1004494

Abstract

Background
Human papillomavirus (HPV) testing of self-collected vaginal samples has potential to improve coverage of cervical screening programmes, but current guidelines mostly require those HPV positive on a self-sample to attend for routine screening.

Methods and findings
A pragmatic modified stepped-wedge implementation feasibility trial was conducted at primary care practices in England. Individuals aged 25 to 64 years who were at least 6 months overdue for cervical screening could provide a self-collected sample. The primary outcomes included the monthly proportion of non-attenders screened, changes in coverage, and uptake within 90 days. Self-samples from 7,739 individuals were analysed using Roche Cobas 4800. Individuals with a positive self-sample were encouraged to attend clinical screening.

In this post hoc study of the trial, we related the HPV type (HPV16, HPV18, or other high-risk type) and cycle threshold (Ct) value on the self-sample to the results of clinician-collected sample and cervical intraepithelial neoplasia grade 2 or worse (CIN2+). We wished to triage HPV–positive individuals to immediate colposcopy, clinician sampling, or 12-month recall depending on risk. A total of 1,001 women tested positive through self-samples, and 855 women who had both an HPV–positive self-sample and a subsequent clinician-sample were included in this study. Of these, 71 (8.3%) had CIN2+. Self-sample Ct values were highly predictive of HPV in the clinician sample. Combining HPV type and Ct value allowed stratification into 3 risk groups; 44/855 (5%) were high-risk of whom 43% (19/44, 95% confidence interval [29.7%, 57.8%]) had CIN2+. The majority (52.9%, 452/855) were low-risk, of whom 4% (18/452, 95% CI [2.5%, 6.2%]) had CIN2+. The main limitation of our study was the colposcopy assessment was restricted to individuals who had abnormal cytology after positive results of both self-sample and clinician-collected sample.

Conclusions
HPV type and Ct value on HPV–positive self-samples may be used for triage. The difference in the risk of CIN2+ in these groups appears sufficient to justify differential clinical management. A prospective study employing such triage to evaluate laboratory workflow, acceptability, and follow-up procedure and to optimise clinical performance seems warranted.

Trial Registration
ISRCTN12759467.

Author summary

Why was this study done?

• Human papillomavirus (HPV) testing of self-collected vaginal samples has potential to improve coverage of cervical screening programmes, but current guidelines mostly require those HPV positive on a self-sample to attend for routine screening.
• The association between HPV cycle threshold (Ct) values (as a proxy for viral load), HPV genotypes, and the risk of high-grade cervical precancerous lesions and cancers has been well established. However, most of the existing studies are based on practitioner-collected cervical samples, with limited research focusing on self-collected samples.

What did the researcher do and find?

• We propose a stratification approach, dividing HPV–positive individuals into 3 distinct risk groups based on HPV Ct values and genotypes (HPV16, HPV18, or other high-risk type) from HPV self-samples.
• We classified 5% (44/855) of the individuals (HPV-16 Ct <30) who tested HPV-positive on their self-sample as high-risk, with 43.2% (19/44) of them having CIN2+, which is comparable to those referred in England with HPV positive and abnormal cytology results.
• The low-risk group (HPV non-16/18 Ct ≥30), comprising half of those with HPV on their self-sample have a risk of CIN2+ of 4.0% (18/452) which is lower than in those who are HPV positive but cytology normal on a routine clinician screen.

What do these findings mean?

• The proposed classifier allows those at greatest risk (high-risk group) to be sent directly to colposcopy and detects 3 quarters of CIN2+ without delay while allowing half of individuals (low-risk group) to be managed by repeat self-sampling. The intermediate risk group could be referred to their general practises for clinical sampling.
• Findings support the potential use of this risk classifier in the management of HPV–positive self-samples within organised cervical screening programmes.
• Limitations of the study include that the colposcopy assessment was restricted to individuals who had abnormal cytology after positive results of both self-samples and clinician-collected samples. Additionally, different HPV assays were used for primary screening and follow-up tests.