Effectiveness of High-risk Human Papillomavirus Testing for Cervical Cancer Screening in China

Abstract

IMPORTANCEEvidence is needed regarding the introduction of high-risk human papillomavirus (hrHPV) testing into China's national cervical cancer screening program.OBJECTIVE To evaluate hrHPV testing as a new screening modality for the national program. DESIGN, SETTING, AND PARTICIPANTSThis population-based, multicenter, open-label, randomized clinical trial took place across 20 primary health care centers in urban and rural areas across China. At least 3000 women aged 35 to 64 years per site were invited to participate, for a total of 60 732 women evaluated.INTERVENTIONS At baseline, women were randomly assigned to cytology, hrHPV testing, or visual inspection with acetic acid and Lugol iodine (VIA/VILI) (rural only). Women who tested positive for hrHPV were randomized into cytology-triage, VIA/VILI-triage (rural only), or direct colposcopy arms. Regarding primary or triaging tests, women with cytological abnormalities or who tested positive with VIA/VILI were referred to colposcopy. After 24 months, combined screening of cytology, hrHPV testing, and VIA/VILI was performed, and all women with positive results were referred to colposcopy. MAIN OUTCOMES AND MEASURESThe primary outcomes were cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ yields. The secondary outcome was colposcopy referral rate.RESULTS A total of 60 732 women were included in this study, with median (interquartile range) age of 47 (41-52) years. Among urban women, 8955 were randomized to cytology and 18 176 to hrHPV genotyping; among rural women, 11 136 were randomized to VIA/VILI, 7080 to cytology, and 15 385 to hrHPV testing. Participants who tested positive for hrHPV with direct colposcopy had higher risk ratios for disease yields at baseline (urban hrHPV vs cytology, CIN2+ 2.2 [95% CI, 1.6-3.2] and CIN3+ 2.0 [95% CI, 1.2-3.3]; rural hrHPV vs cytology, 2.6 [95% CI, 1.9-4.0] and 2.7 [95% CI, 2.0-3.6]; rural hrHPV vs VIA/VILI, 2.0 [95% CI, 1.6-2.3] and 2.3 [95% CI, 1.8-3.1]). At 24 months, baseline-negative women in the hrHPV arm had significantly lower risk ratios than those with cytology, or VIA/VILI for CIN2+ (0.3 [95% CI, 0.2-0.5], 0.3 [95% CI, 0.2-0.6]) and CIN3+ (0.3 [95% CI, 0.1-0.6], 0.4 [95% CI, 0.2-0.8]) in rural sites. The colposcopy referral rate for hrHPV-positive rural women was reduced to 2.8% by cytology triage, with significantly higher CIN2+ yields than cytology (2.1 [95% CI, 1.3-2.6]) or VIA/VILI arm (1.6 [95% CI, 1.03-2.1]). Genotyping for hrHPV with cytology triage significantly reduced the colposcopy referral rate compared with cytology (0.8 [95% CI, 0.7-0.9]) for urban women. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, testing for hrHPV was an effective primary screening method in primary health care centers. Incorporating hrHPV testing (polymerase chain reaction-based for urban areas, hybrid capture-based for rural areas) into China's national screening program is reasonable.

Real-world effectiveness of primary screening with high-risk human papillomavirus testing in the cervical cancer screening programme in China: a nationwide, population-based study

“…This study showed that HPV testing detected more CIN2+ than cytology, suggesting its benefit in the first round of screening as expected from the results of the previous randomized controlled trials [2,3,22,23]. Furthermore, our study, for the first time, showed that the relative effectiveness of HPV testing versus cytology was consistent in lower-and upper-middle-income areas, supporting the generalizability of its benefit to middleincome areas.…”

Performance of cervical cancer screening and triage strategies among women living with HIV in China

“…A large-scale randomized clinical trial in China has demonstrated the effectiveness of high-risk HPV test as primary screening method in primary healthcare centers. 20 In China, HPV assay is running on the fast lane of development, as of 2020, hundreds of HPV detection products have been approved by the National Medical Products Administration. Affordable, sensitive, userfriendly, rapid, and robust "point-of-care" HPV technology is now under validation.…”

“…The median age was 40 (35-47) years, 60.2% have been married, 71.2% had education at junior high school or below, 48.1% were unemployed, and 42.7% were farmer or rural migrant worker. Median age at sexual debut and first delivery was 20 (19)(20)(21)(22) and 24 (22-27) years, respectively. The median years living with HIV and duration on cART was 5 (2-9) and 4 (2-8) years.…”

The Expression of HPV E6/E7 mRNA in Situ Hybridization in HPV Typing-negative Cervical Cancer

“…It is well established that persistent infection with oncogenic HPV subtypes is necessary for the contribution to CC [7] and results in nearly all cases of CC [1]. A multicentre, open-label, randomized clinical trial concluded that the primary screening of HR-HPV for cervical cancer was effective [15], and HPV typing detection is widely used in CC screening programs at present. However, a previous study in SCC using FDA-approved cervical screening technologies showed that HPV testing can be negative in patients with SCC diagnosed by liquid-based cytology [16].…”