Effect of Screening With Primary Cervical HPV Testing vs Cytology Testing on High-grade Cervical Intraepithelial Neoplasia at 48 Months: The HPV FOCAL Randomized Clinical Trial

Abstract

(Abstracted from JAMA 2018;320:43–52) There are only limited data in North American populations on the relative diagnostic effectiveness of cervical cancer screening with primary human papillomavirus (HPV) testing alone compared with cytology.

Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial

“…The HPV FOCAL RCT [16][17][18] (ISRCTN79347302) compared HPV (Hybrid Capture ® 2 High-Risk HPV DNA Test ® [HC2]; Qiagen Inc., Germantown, MD, USA) (Intervention and Safety [HPV] Arms) versus LBC screening (Control Arm) in women aged 25-65. HC2 positive (HC2+) women in the HPV Arms were triaged by LBC, with immediate colposcopy referral for abnormal cytological findings.…”

Disease detection at the 48‐month exit round of the HPV FOCAL cervical cancer screening trial in women per‐protocol eligible for routine screening

“…5,7,8,24 Randomized trials have demonstrated that screening which includes primary HPV testing is superior to those based on cytology alone, 9,[11][12][13][14]25 including the study from which the sample used in this article was drawn. 15 Studies from large insured populations in the US have come to similar conclusions. 26,27 However, the magnitude of the difference in CIN3+ prevalence at exit screening between the two arms seen in this HPV FOCAL PPE analysis is nonsignificant.…”

“…7,8 Comparison of HPV vs. cytology screening in randomized trials has resulted in considerable evidence supporting the use of HPV-based screening for increased detection of CIN2+ at initial screening rounds and reduced subsequent development of cervical cancer and its precursors. [9][10][11][12][13][14][15] Replacement of cytology with HPV-based screening requires reconsidering screening intervals, ages eligible and triage testing to optimize the balance between benefits and harms.…”

“…Twenty-four-month screen results have also been published for the safety and control arms 19 which found lower LBC identified disease prevalence at 24 months in those initially screened with HPV compared to those screened with cytology. Results, on an intention to screen basis, have been published 15 comparing exit and cumulative rates of disease for the control and intervention arms, which found that a single round of HPV detected more disease earlier than two rounds of cytology and that those HPV negative at baseline had lower 4-year disease risk than those cytology negative at baseline. Despite consistent observations regarding the superior sensitivity of HPV testing vs. cytology, there are some concerns expressed in both the lay press and literature 20 regarding the safety of extended HPV based screening intervals among individual women.…”

Insertional oncogenesis by HPV70 revealed by multiple genomic analyses in a clinically HPV‐negative cervical cancer

“…Population screening for women for cervical cancer historically has been accomplished by cytology (Papanicolaou test), but multiple clinical trials have provided evidence of improved sensitivity of hrHPV testing for detection of cervical cancer precursor lesions compared to cytology alone over multiple rounds of screening and follow-up. [9][10][11][12][13] The HPV types included in the screening assays are based on epidemiological prevalence data that balance sensitivity and specificity so as not to overtriage women to secondary screening such as colposcopy, and they currently include at most the 14 hrHPV types. Exclusion of less prevalent types from HPV screening reduces possible iatrogenic morbidity from subsequent colposcopy and excisional procedures following detection of viral types of uncertain pathological significance, and also reduces the costs involved in more extensive testing.…”