SHENCCAST II
1. Am J Clin Pathol. 2011 May;135(5):790-5. doi: 10.1309/AJCPKA6ATAPBZ6JQ.
A population-based clinical trial comparing endocervical high-risk HPV testing using hybrid capture 2 and Cervista from the SHENCCAST II Study.
Belinson JL(1), Wu R, Belinson SE, Qu X, Yang B, Du H, Wu R, Wang C, Zhang L,
Zhou Y, Liu Y, Pretorius RG.
Author information:
(1)Preventive Oncology International, Cleveland Heights, OH, USA.
Our objective was to directly compare the accuracy of the high-risk human
papillomavirus (HPV) assays, Hybrid Capture 2 (hc2; Qiagen, Gaithersburg, MD)
and Cervista (Hologic, Bedford, MA), in diagnosing cervical intraepithelial
neoplasia (CIN) 3 or worse (cancer). A population-based, cross-sectional study
(The Shenzhen Cervical Cancer Screening Trial II) was conducted in Guangdong
Province in China. Three high-risk HPV assays, self and direct cervical sampling
and cytology, were studied. Abnormal results on any of 6 study tests (33%)
resulted in referral to colposcopy. At colposcopy, every patient had at least 5
cervical biopsy specimens obtained. For 8,556 women between the ages of 25 and
59 years (mean, 38.9 years), the rate for CIN 3 or worse was 1.6% (141/8,556).
The sensitivity (confidence interval) values for CIN 3 or worse were 97.9%
(94.0%-99.6%) and 95.1% (90.0%-98.0%) for hc2 and Cervista, respectively (P >
.05). The specificity (confidence interval) values were 87.8% (87.1%-88.5%) and
90.3% (89.6%-90.9%), respectively (P < .05). Differences in accuracy in
diagnosing CIN 3 or worse with the hc2 and Cervista tests are minor and result
from the decisions made in selecting the cut points.
DOI: 10.1309/AJCPKA6ATAPBZ6JQ
PMID: 21502436 [Indexed for MEDLINE]
2. Am J Clin Pathol. 2011 Dec;136(6):920-3. doi: 10.1309/AJCPJDAORUY4EYR6.
A new PCR-based mass spectrometry system for high-risk HPV, part II: clinical trial.
Du H(1), Yi J, Wu R, Belinson SE, Qu X, Yang B, Wang C, Yi X, Belinson JL.
Author information:
(1)Peking University Shenzhen Hospital, China.
This was a population-based clinical trial of a polymerase chain reaction-based
multiplex high-risk human papillomavirus (HR-HPV) assay using mass spectrometry
(MassARRAY [Sequenom, San Diego, CA] matrix-assisted laser desorption/ionization
time-of-flight mass spectrometry system [MALDI-TOF]). Participants were 10,000
women between the ages of 25 and 59 years in Guangdong Province, China
(SHENCCAST II Study). All women collected a self-sample (tested with Cervista
[Hologic, Marlborough, MA] and MALDI-TOF) followed by a clinician-collected
cervical sample (for cytology, Hybrid Capture 2 [HC2; Qiagen, Gaithersburg, MD],
Cervista, and MALDI-TOF). Patients with any abnormal result were asked to return
for colposcopy and biopsies. This analysis included the data for 8,556 women.
The sensitivity values for cervical intraepithelial neoplasia (CIN) 3 or worse
for a direct cervical sample were 97.9%, 95.1%, and 94.3 for HC2, Cervista, and
MALDI-TOF, respectively (P > .05). The sensitivity for CIN 3 or worse for a
self-collected sample tested with MALDI-TOF was also 94.3%, which was similar to
a clinician-obtained endocervical sample assayed with the 3 HR-HPV assays.
MALDI-TOF combined with a self-collected sample provides a highly sensitive,
high-throughput, low-cost-per-case assay for mass screening.
DOI: 10.1309/AJCPJDAORUY4EYR6
PMID: 22095378 [Indexed for MEDLINE]
3. J Low Genit Tract Dis. 2012 Oct;16(4):416-20. doi: 10.1097/LGT.0b013e31824f48c8.
Secondary screening after primary self-sampling for human papillomavirus from SHENCCAST II.
Wu R(1), Du H, Belinson SE, Pretorius RG, Zou J, Yang B, Wang C, Belinson JL.
Author information:
(1)Peking University Shenzhen Hospital, Shenzhen, China.
OBJECTIVE: We recently demonstrated that a self-collected sample tested with a
high-throughput polymerase chain reaction-based high-risk human papillomavirus
(HR-HPV) assay is equal in sensitivity to a physician-obtained direct
endocervical sample. We now explore some secondary screening options to improve
specificity.
METHODS: The Shenzhen Cervical Cancer Screening Trial II is a multisite,
population-based cross-sectional cervical cancer screening study conducted in
Guangdong Province, China. Two HR-HPV assays were used for self-collected
specimens, and 3 assays were used for directly collected specimens along with
cytology. The polymerase chain reaction-based matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry assay reported 14 HR-HPV
types. Any patient with a positive lesion on any assay or cytology underwent
colposcopy and biopsy.
RESULTS: A total of 8,556 women with a mean age of 38.9 years (range = 25-54
years) were included in the analysis. Primary self-collection had a sensitivity
of 94.3% and a specificity of 87.5% (for cervical intraepithelial neoplasia
grade 3 or cancer). Secondary cervical cytology had a sensitivity and
specificity of 83.0% and 95.2%, respectively, which would require a pelvic
examination and sacrifice some sensitivity. Secondary genotyping for HPV types
16 or 18 had a sensitivity and specificity of 53.9% and 97.7%, respectively; and
HPV types 16, 18, 31, 33, 45, 52, and 58 had a sensitivity and specificity of
92.2% and 90.4%, respectively.
CONCLUSIONS: Genotyping is efficient if it is part of the primary test result.
It potentially identifies a high percentage of the cancers (types 16/18 = 84.5%
in China).
DOI: 10.1097/LGT.0b013e31824f48c8
PMID: 22659777 [Indexed for MEDLINE]
4. J Low Genit Tract Dis. 2014 Apr;18(2):122-7. doi: 10.1097/LGT.0b013e31829f2171.
Triage of women with negative cytology and positive high-risk HPV: an analysis of data from the SHENCCAST II/III studies.
Goodrich SK(1), Pretorius RG, Du H, Wu R, Belinson JL.
Author information:
(1)1Women’s Health Institute, Department of Gynecology, Cleveland Clinic,
Cleveland, OH; 2Department of Obstetrics and Gynecology, S.C.P.M.G. Fontana,
Fontana, CA; 3Department of Obstetrics and Gynecology, Peking University
Shenzhen Hospital, Shenzhen, China; and 4Preventive Oncology International,
Cleveland Heights, OH.
OBJECTIVES: To determine a management strategy for women testing negative with
cervical cytology and positive for high-risk human papillomavirus (HR-HPV).
METHODS: Using the data from the large population-based Shenzhen Cervical Cancer
Screening Trials II and III (SHENCCAST II/III), we compared the risk for
cervical intraepithelial neoplasia grade 3 or cancer (CIN 3+) in women with
negative cytology but testing positive for HR-HPV DNA using Cervista HPV HR or
matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
(MALDI-TOF), followed by secondary screening with type-specific Cervista
HPV-16/18 or MALDI-TOF. The study aim was to seek the most sensitive and
specific triage assay for referral for colposcopy.
RESULTS: A total of 8,556 women had complete data. The proportion of women with
negative cytology and positive HR-HPV by Cervista HR-HPV (5.30%, 453/8,556) was
slightly lower than that of women with negative cytology and HR-HPV-positive
tests by MALDI-TOF (5.82%, 499/8,556, p = .015). The proportion of women having
negative cervical cytology and a positive HR-HPV by Cervista HR who have HPV-16
and/or -18 by Cervista HPV-16/18 (11.8%, 53/448) was less than that of women
with a negative cervical cytology and positive HR-HPV by MALDI-TOF who have
HPV-16 and/or -18 by MALDI-TOF (19.4%, 97/499, p = .001). The proportion of CIN
3+ within negative cervical cytology and positive HR-HPV that were HPV-16 and/or
-18 for the Cervista 16/18 assay (61.5%, 8/13) was similar to that for the
MALDI-TOF 16/18 assay (66.7%, 10/15, p = 0.8).
CONCLUSIONS: In the cytology-negative HR-HPV-positive population, Cervista 16/18
as the HPV detection method would refer 11.8% of women for colposcopy and
diagnose 61.5% of the CIN 3+, while MALDI-TOF16/18 would refer 19.4% and
diagnose 66.7% of the CIN 3+. Cervista HPV-16/18 seems to be the superior triage
test. However, in resource-limited settings, an assay that includes 16/18
genotyping in the primary result (rather than a second test) may be more cost
efficient.
DOI: 10.1097/LGT.0b013e31829f2171
PMID: 24270196 [Indexed for MEDLINE]
5. Zhonghua Fu Chan Ke Za Zhi. 2015 Apr;50(4):263-7.
[Diagnostic value of multiply biopsies and endocervical curettage on cervical
lesions].
[Article in Chinese]
Zhang L(1), Du H, Zhang W, Yang B, Wang C, Belinson JL, Wu R(2).
Author information:
(1)Shenzhen Key Laboratory of Gynecological Diagnostic Technology Research,
Peking University Shenzhen Hospital, Shenzhen 518036, China.
(2)Email: wurf100@126.com.
OBJECTIVE: To investigate the value of multiply biopsies and endocervical
curettage (ECC) on diagnosing cervical lesions.
METHODS: For the detection of cervical lesions, Shenzhen cervical cancer
screening trial II (SHENCCAST II) program combined methods of HPV screening with
liquid-based cytology (LBC), any positive indicators was then performed multiply
biopsies and ECC under colopscopy. A total of 2,558 clear colposcopic images and
pathological diagnoses were reviewed. To analyse the pathological results and
primary screening results of the negative colopscopic images for discussing the
value of multiply biopsies and ECC.
RESULTS: Overall 2,558 women’s colposcopic images and sampling results were
completed and validated. 69.98% (1,790/2,558) women had normal colposcopy
appearances. Among them, 2.23% (40/1,790) were diagnosed as cervical
intraepithelial neoplasia II or worse (CIN II+). The odds ratio of high-grade
squamous intraepithelial lesion (HSIL) was 28.37 (P=0.000) and atypical squamous
cell cannot exclude HSIL (ASC-H) was 15.07 (P=0.001). HPV types 16, 52, 58, 31,
33 and 18 were related to high-grade cervical lesion with the odds ratio of 3.11
(P=0.017). Hybrid capture II (HC-II) DNA test results shown that women with HPV
positive were 3.58 times more risky than those of HPV negative, which was
related to high-grade cervical lesion (P=0.025). Among the 2,558 women, CIN II+
detective rate from ECC were 40.7% (44/108) in older group (≥40 years) were
higher than that of 19.2% (24/125) in younger group (<40 years; χ2=13.01,
P=0.000). CIN II+ detective rate from multiply biopsies were 90.7% (98/108) in
older group (≥40 years) were higher than that of 88.8% (111/125) in younger
group (<40 years; χ2=0.24, P>0.05). The highest risky items of detecting CIN II+
were as follows: (1) HSIL or ASC-H; (2) HPV types 16, 18, 52 and 58 positive
(either one); (3) HC-II HPV positive, at least 2 of the 3 items were included
among 32 cases of the 40 CIN II+ with normal colposcopy appearances.
CONCLUSIONS: The results shown that only performed multi-site biopsies with
abnormal colposcopy appearances may be missed some highgrade cervical lesion.
For the positive indicators during screening should be performed randomly
multi-sites biopsies and ECC under colopscopy, which may be helpful to reduce
miss diagnosis.
PMID: 26080937 [Indexed for MEDLINE]
6. J Med Screen. 2016 Mar;23(1):38-43. doi: 10.1177/0969141315604863. Epub 2015 Oct
14.
Evaluation of The Cervista HPV A9 group In Screening Patients for Cervical Cancer.
Zhao J(1), Du H(2), Belinson JL(3), Qu X(3), Zhang W(2), Mei J(1), Yang B(4),
Wang C(2), Zhang L(2), Wu R(5).
Author information:
(1)Peking University Shenzhen Hospital, Shenzhen, PR China.
(2)Peking University Shenzhen Hospital, Shenzhen, PR China Shenzhen Key
Laboratory on Technology for Early Diagnosis of Major Gynecological diseases,
Shenzhen, PR China.
(3)Preventive Oncology International, Inc. Cleveland Heights, USA and Cleveland
Clinic, Women’s Health Institute, Cleveland, USA.
(4)Cleveland Clinic, Department of Anatomic Pathology, Cleveland, USA.
(5)Peking University Shenzhen Hospital, Shenzhen, PR China Shenzhen Key
Laboratory on Technology for Early Diagnosis of Major Gynecological diseases,
Shenzhen, PR China wurf100@126.com.
OBJECTIVE: To exploit the prevalence of HPV genotypes 52/58 in a Chinese
population, we evaluated algorithms that the use the Cervista Assay A9 group for
primary cervical cancer screening.
METHODS: The SHENCCAST II trial database was re-analyzed, focussing on the A9
pool of the Cervista HR-HPV Assay. Results for the detection CIN2+ and CIN3+
were correlated with a genotyping assay (MALDI-TOF) and cervical cytology to
explore various screening algorithms.
RESULTS: This analysis included 8,556 women with a mean age of 38.9. CIN 2+
rates were 2.7% (233/8556); CIN 3+ rates were 1.7% (141/8556). Overall HPV
infection rates were 11.1% (950/8556) for Cervista, in which A5/A6, A7 and A9
groups were 26.5% (227/950), 22.9% (218/950) and 67.8% (644/950), respectively.
The HPV A9 group is highly predictive of high-grade cervical lesions (CIN2+
OR = 103.61, CIN3+ OR = 128.059). Sensitivity and specificity for Cervista A9
group for CIN 2+ was 85.4% and 94.7%, and for CIN 3+ 89.4% and 93.8%
respectively. Cervista A9 Assay followed by triage cytology for non-A9 positives
has sensitivity and specificity for CIN2+ of 91.5% of 93.5%, and for CIN 3+
94.3% and 92.6%.
CONCLUSION: Using the Cervista A9 as the primary screen instead of the full
Cervista assay, the percentage referred to colposcopy would decrease from 11.1%
to 8.8% and percentage requiring cytology would decrease from 11.1% to 3.6%.
Sensitivity of detecting CIN 2+(91.5%), CIN3+(94.3%) would remain similar to the
complete Cervista HR-HPV assay for CIN 2+(93.1%), CIN3+(95.0%).
© The Author(s) 2015.
DOI: 10.1177/0969141315604863
PMID: 26466824 [Indexed for MEDLINE]
7. PLoS One. 2019 Jul 26;14(7):e0220200. doi: 10.1371/journal.pone.0220200.
eCollection 2019.
Evaluation of alternately combining HPV viral load and 16/18 genotyping in secondary screening algorithms.
Luo H(1)(2), Du H(2)(3), Belinson JL(4)(5), Wu R(2)(3).
Author information:
(1)Department of Obstetrics and Gynecology, Peking University People’ Hospital,
Beijing, PR China.
(2)Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital,
Shenzhen, PR China.
(3)Shenzhen Key Laboratory on Technology for Early Diagnosis of Major
Gynecological diseases, Shenzhen, PR China.
(4)Gynecologic Oncology Division, Women’s Health Institute, Cleveland Clinic,
Cleveland, OH, United States of America.
(5)Preventive Oncology International, Cleveland Heights, OH, United States of
America.
BACKGROUND: Correlation with HPV viral load and worsening cervical lesions had
been reported, but its potential for triage after primary HPV screening has not
been adequately explored, especially when combined with HPV-16/18 genotyping.
OBJECTIVE: To evaluate combinations of human papillomavirus (HPV) viral load and
genotyping for HPV-16/18 as secondary screening strategies.
METHODS: The Shenzhen Cervical Cancer Screening Trial Ⅱ (SHENCCAST Ⅱ) database
was re-analyzed to explore new screening algorithms using the results of Hybrid
Capture 2 (HC2), Mass Array Matrix-Assisted Laser Desorption/Ionization
Time-of-Flight Mass spectrometry System (MALDI-TOF-MS) and the ThinPrep
cytologic test (TCT) obtained by endocervical sampling.
RESULTS: Compared with the recommended screening strategy of genotyping
HPV-16/18 plus reflex to cytology, using viral load (10 RLU/CO as threshold)
plus reflex to cytology resulted in less cytology but had a significantly higher
sensitivity for cervical intraepithelial neoplasia 2+ (CIN2+)/CIN3+ without
considerable changes in specificity and referral rates. Both of the strategy of
using viral load ≥10 RLU/CO as cut-point for immediate colposcopy followed by
triage genotyping HPV-16/18 for the other positive (≥1<10 RLU/CO) and the
strategy of referring HPV-16/18 positives for immediate colposcopy followed by
triage viral load (10 RLU/CO as threshold) for non-HPV-16/18 positives had
comparable screening efficacy with algorithims that contain cytology.
CONCLUSIONS: Primary HPV screening with triage of HPV-positive women by a
combination of viral load and genotyping for HPV-16/18 provides good balance
between sensitivity and specificity, the number of tests required, and referral
rates.
DOI: 10.1371/journal.pone.0220200
PMCID: PMC6660090
PMID: 31348794 [Indexed for MEDLINE]
Conflict of interest statement: The authors have declared that no competing
interests exist.
8. J Low Genit Tract Dis. 2019 Oct;23(4):241-247. doi:
10.1097/LGT.0000000000000485.
Key Determinants of the Value of Random Cervical Biopsy at Colposcopy.
Pretorius RG(1), Belinson JL(2), Burchette RJ(3), Wu R(4), Qiao YL(5).
Author information:
(1)Department of Obstetrics and Gynecology, Southern California Permanente
Medical Group-Fontana, Fontana, CA.
(2)Medworks, Cleveland, OH.
(3)Department of Research and Evaluation, Southern California Permanente Medical
Group-Los Robles, Los Robles, CA.
(4)Department of OB/GYN, Peking University Shenzhen Hospital, Shenzhen, China
and the Key Laboratory on Technology for Early Diagnosis of Major Gynecological
Diseases, Shenzhen, China.
(5)Department of Epidemiology, Cancer Institute/Hospital, Chinese Academy
Medical Sciences, Beijing, China.
OBJECTIVE: The aim of the study was to assess whether lower proportions of
cervical intraepithelial neoplasia 2+ diagnosed by random biopsy are from lower
cut points defining an abnormal colposcopic impression or obtaining only one
random biopsy when colposcopic impression is normal.
METHODS: We compared colposcopy experiences within Shanxi Province Cervical
Cancer Screening Study (SPOCCS) (n = 1,383) and Shenzhen Cervical Cancer
Screening Trial (SHENCCAST) (n = 631), which had instructive differences in the
cut point defining an abnormal colposcopic impression.
RESULTS: The proportion of CIN 2+ diagnosed by random biopsy in SPOCCS (35.0%,
141/403) was higher than SHENCCAST (18.4%, 35/190, p < .001). Quadrant-specific
receiver operating characteristic curves for diagnosis of CIN 2+ by colposcopic
impression in SPOCCS and SHENCCAST were similar; a lower cut point for an
abnormal colposcopic impression in SHENCCAST resulted in lower proportion of CIN
2+ diagnosed by random biopsy. Normal colposcopic impression was found in 85.1%
(120/141) of cases of CIN 2+ diagnosed by random biopsy in SPOCCS and in 57.1%
(20/35) of such cases in SHENCCAST. Of CIN 2+ diagnosed by random cervical
biopsy with normal colposcopic impression, one cervical quadrant was involved
with CIN 2+ in 66.7% (80/120) of colposcopies in SPOCCS and 80% (16/20) of
colposcopies in SHENCCAST.
CONCLUSIONS: Colposcopy series with higher proportions of CIN 2+ diagnosed by
random biopsy likely have more stringent cut points defining an abnormal
colposcopic impression and have more random biopsies when the colposcopic
impression is normal. At colposcopy, we advise multiple biopsies of all
acetowhite epithelium or multiple random biopsies to increase the sensitivity of
colposcopy.
DOI: 10.1097/LGT.0000000000000485
PMID: 31592970 [Indexed for MEDLINE]
9. Zhonghua Fu Chan Ke Za Zhi. 2021 Apr 25;56(4):271-279. doi:
10.3760/cma.j.cn112141-20200824-00357.
[Performance of vaginal self-sampling high-risk HPV genotyping as primary and
combining cytology or viral load as secondary in cervical cancer screening].
[Article in Chinese; Abstract available in Chinese from the publisher]
Guo CL(1), Luo HX(2), Wang C(1), Qu XF(1), Yang B(3), Belinson JL(3), Du H(1),
Wu RF(1).
Author information:
(1)Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital,
Institute of Obstetrics and Gynecology, Shenzhen Peking University-Hong Kong
University of Science and Technology Medical Center, Shenzhen Key Laboratory on
Technology for Early Diagnosis of Major Gynecological Diseases, Shenzhen 518000,
China.
(2)Department of Obstetrics and Gynecology, Peking University People’s Hospital,
Beijing 100044, China.
(3)Preventive Oncology International, Inc, Shaker Heights, USA and Cleveland
Clinic, Women’s Health Institute, Cleveland, OH, USA, 44109.
Objective: To evaluate the efficacy of high-risk HPV (HR-HPV) genotyping with
vaginal self-sampling in primary screening and combining cytology or viral load
for HR-HPV positive as secondary screening strategies. Methods: The data
referring to HR-HPV genotyping of self-collected sample with mass array
matrix-assisted laser desorption-ionization time-of-flight mass spectrometry
(MALDI-TOF-MS), HR-HPV viral load of physician-collected sample with hybrid
capture Ⅱ (HC-Ⅱ), liquid-based cytology and histology of 8 556 women were from
Shenzhen cervical cancer screening trial Ⅱ (SHENCCAST-Ⅱ) conducted between April
2009 and April 2010. The data were reanalyzed to determine the sensitivity and
specificity to cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN
Ⅱ+), CIN of grade 3 or worse (CIN Ⅲ+) when HR-HPV genotyping combining with
colposcopy as primary screening strategy based on varied HR-HPV subtype
(strategy 1, including 5 sub-strategies: 1a: HPV 16/18 positive; 1b: HPV
16/18/58 positive; 1c: HPV 16/18/58/31/33 positive; 1d: HPV 16/18/58/31/33/52
positive; 1e: any HR-HPV positive). The data were also compared to determine the
efficacy of cytology (strategy 2, including 5 sub-strategies: 2a, 2b, 2c, 2d,
2e) or HR-HPV viral load (strategy 3, including 4 sub-strategies: 3a, 3b, 3c,
3d) of physician-collected sample as a triage with HR-HPV genotyping for
self-sampling HR-HPV positives. Results: (1) The HR-HPV positive rate was 13.77%
(1 178/8 556) in the self-collected samples of 8 556 pregnant women. Of them,the
prevalences of HPV 16/18, HPV 16/18/58, HPV 16/18/58/31/33 and HPV
16/18/58/31/33/52 were 3.16% (270/8 556), 5.14% (440/8 556), 6.66% (570/8 556)
and 9.81% (839/8 556), respectively. The HR-HPV viral load ≥10 relative light
units/control (RLU/CO) was 8.87%(759/ 8 556), while cytological results
≥atypical squamous cell of undetermined signification (ASCUS) were 12.05% (1
031/8 556). (2) The strategy 1e had the highest sensitivities for CIN Ⅱ+, CIN Ⅲ+
which were 92.70% and 94.33%,respectively,among 14 sub-strategies,while the
lowest specificity and positive predictive value (PPV). Meanwhile,the required
colposcopy referral rates were much higher than other 13 sub-strategies
(13.77%). The other 4 sub-strategies of strategy 1 (1a, 1b, 1c, 1d), strategy 1a
had the highest specificities for CIN Ⅱ+ and CIN Ⅲ+ (97.92%, 97.69%,
respectively), while 1d had the highest sensitivities for CIN Ⅱ+ and CIN Ⅲ+
(88.41%, 92.20%, respectively). (3) Both strategies of referring self-sampling
HPV 16/18 positives for immediate colposcopy followed by triage
physician-collected sample cytology (≥ASCUS) or viral load (≥10 RLU/CO) for
non-HPV 16/18 positives had significantly higher sensitivity and specificity for
CIN Ⅱ, CIN Ⅲ+, as well as lower referral rates (strategy 2a and 3a).
Additionally, based on these two secondary screening strategies, cumulatively
using the other four HR-HPV (HPV 58, 31, 33 and 52) positives as triage for
immediate colposcopy showed an enhanced sensitivity. Conclusions: Primary HR-HPV
cervical cancer screening strategy based on self-sampling with triage of
cytology (≥ASCUS) or viral load (≥10 RUL/CO) provides a good balance among
sensitivity, specificity for CIN Ⅱ+ and CIN Ⅲ+ and the number of tests required,
referral rates. The efficacy of HR-HPV genotyping combining cytology or viral
load secondary screening strategies will have a spiral escalation when HPV 58,
31, 33, 52 are included.
Publisher: 目的：
评价阴道自取样本高危型HPV（HR-HPV）分型检测用于子宫颈癌初筛的筛查效率，并探讨以不同HR-HPV亚型组合联合医生取样本的细胞学检查或HR-HPV病毒载量检测对自取样本HR-HPV阳性者进行二次筛查的筛查效率。
方法：
本研究的数据来自2009年4月至2010年4月深圳市子宫颈癌筛查项目Ⅱ（SHENCCAST-Ⅱ）数据库，收集其中有自取样本的基质辅助激光解吸电离-飞行时间质谱分析（MALDI-TOF-MS）技术进行的HR-HPV分型检测结果以及医生取样本的第2代杂交捕获技术（HC-Ⅱ）检测的HR-HPV病毒载量结果、子宫颈细胞学检查结果的妇女共8
556例，转诊阴道镜检查者均有活检组织病理检查结果。分析自取样本HR-HPV分型检测作为子宫颈癌初筛方案（即方案1）时，基于其不同HR-HPV亚型组合［包括5个亚方案，即1a：HPV
16和（或）18型（HPV 16/18型）阳性；1b：HPV 16/18/58型阳性；1c：HPV 16/18/58/31/33型阳性；1d：HPV
16/18/58/31/33/52型阳性；1e：所有14种HR-HPV亚型中任一亚型阳性］的阴道镜转诊方案检出子宫颈上皮内瘤变（CIN）Ⅱ及以上病变（CIN
Ⅱ+）、CIN Ⅲ及以上病变（CIN
Ⅲ+）的敏感度与特异度；并以自取样本HR-HPV初筛阳性者即以方案1中的各亚方案为基础，对比分析其联合医生取样本的细胞学检查（即方案2，包括2a、2b、2c、2d、2e共5个亚方案）或HR-HPV病毒载量检测（即方案3，包括3a、3b、3c、3d共4个亚方案）作为分流指标的二次筛查方案的筛查效率。
结果： （1）本研究纳入的8 556例妇女的年龄为（38.9±7.9）岁，自取样本检测的HR-HPV阳性率为13.77%（1 178/8 556），其中HPV
16/18型、HPV 16/18/58型、HPV 16/18/58/31/33型和HPV
16/18/58/31/33/52型组合的阳性率分别为3.16%（270/8 556）、5.14%（440/8 556）、6.66%（570/8
556）和9.81%（839/8 556）。医生取样本的HR-HPV病毒载量≥10相对光单位/临床阈值（RLU/CO）者占8.87%（759/8
556），细胞学结果≥未明确诊断意义的不典型鳞状上皮细胞（ASCUS）者占12.05%（1 031/8
556）。（2）方案1中，所有14种HR-HPV亚型中任一亚型阳性者（即方案1e）行阴道镜检查对检出CIN Ⅱ+、CIN
Ⅲ+的敏感度在所有方案（包括3个方案共14个亚方案）中最高（分别为92.70%、94.33%），但是特异度和阳性预测值（PPV）在所有方案中最低（特异度分别为88.44%、87.58%，PPV分别为18.34%、11.29%），且阴道镜检查率在所有方案中最高（为13.77%）。方案1的其他亚方案（即方案1a、1b、1c、1d）中，检出CIN
Ⅱ+、CIN
Ⅲ+的特异度方案1a最高，分别为97.92%、97.69%，其他亚方案也较高，均达90%以上；但敏感度方案1d最高（分别为88.41%、92.20%）。（3）HPV
16/18型阳性者直接行阴道镜检查（即方案1a），非HPV
16/18型阳性者行医生取样本细胞学检查或HR-HPV病毒载量检测，细胞学结果达到阈值（≥ASCUS，即方案2a）或病毒载量达到阈值（≥10
RUL/CO，即方案3a）者行阴道镜检查，其阴道镜转诊率低，而筛查CIN Ⅱ+、CIN
Ⅲ+的敏感度和特异度则较高。若在此两个二次筛查方案基础上，首先根据自取样本HR-HPV分型检测结果，依次增加另外4种HR-HPV亚型（即HPV
58、31、33和52型）阳性者行阴道镜检查，再以细胞学检查或病毒载量检测结果进行二次分流，筛查CIN Ⅱ+、CIN Ⅲ+的敏感度也相应提高。 结论：
以自取样本HR-HPV分型检测为子宫颈癌初筛方案，以及其联合细胞学检查或病毒载量检测进行二次筛查的方案，可以在筛查CIN Ⅱ+、CIN
Ⅲ+的敏感度、特异度以及阴道镜检查率之间获得较好的平衡；将HPV 58、31、33、52型纳入HPV
16/18型阳性的初筛分流指标，并联合细胞学检查或病毒载量检测的序贯二次筛查，可进一步提高筛查效率。.
DOI: 10.3760/cma.j.cn112141-20200824-00357
PMID: 33902239 [Indexed for MEDLINE]
10. J Clin Epidemiol. 2021 Nov;139:319-329. doi: 10.1016/j.jclinepi.2021.06.009.
Epub 2021 Jun 20.
The prevalence of HR-HPV infection based on self-sampling among women in China exhibited some unique epidemiologic features.
Du H(1), Luo H(2), Wang C(1), Qu X(3), Belinson JL(4), Wu R(5).
Author information:
(1)Department of Gynecology and Obstetrics, Peking University Shenzhen Hospital,
Shenzhen, China; Shenzhen Key Laboratory on Technology for Early Diagnosis of
Major Gynecological Diseases, Shenzhen, PR, China; Institute of Obstetrics and
Gynecology, Shenzhen PKU-HKUST Medical Center, Shenzhen,China.
(2)Department of Gynecology and Obstetrics, Peking University People’ Hospital,
Beijing, PR China.
(3)Institute of Obstetrics and Gynecology, Shenzhen PKU-HKUST Medical Center,
Shenzhen,China.
(4)Cleveland Clinic Lerner College of Medicine, Women’ s Health Institute,
Cleveland, Ohio; Preventive Oncology International, Shaker Heights, Ohio.
(5)Department of Gynecology and Obstetrics, Peking University Shenzhen Hospital,
Shenzhen, China; Shenzhen Key Laboratory on Technology for Early Diagnosis of
Major Gynecological Diseases, Shenzhen, PR, China; Institute of Obstetrics and
Gynecology, Shenzhen PKU-HKUST Medical Center, Shenzhen,China. Electronic
address: wurfpush@126.com.
Objective To investigate the epidemiological characteristics of high-risk human
papillomavirus(HR-HPV) infection based on vaginal self-collected samples. Study
Design and Setting The pooled data of 3045 self-collected samples used for the
analysis derived from four previous studies on cervical cancer screening(The
Chinese Multi-Center Screening Trial, CHIMUST; The Shenzhen Cervical Cancer
Screening Trial-2, SHENCCAST-2; The Chinese Cervical Cancer Prevention Study,
CHIPCAPS; Pingshan trial, PINGSHAN)conducted across China by our team since
2011. These cases were evaluated for HR-HPV type prevalence relative to lesion
grade and age. The occurrence of cervical intraepithelial neoplasia(CIN) with
specific HPV types and the influence of co-infection is explored. Results The
top three most common genotypes among the HR-HPV positives were HPV-52(23.4%),
HPV-16(18.0%), and HPV-58(15.50%). For women with CIN2+, the most frequent
genotypes were HPV-16, 58, 52, and 18 in sequence. HPV-16 accounted for the
majority of CIN2/CIN3/Ca with attribution rate of 23.86%, 44.78% and 50.00%
respectively. HPV-58 accounted for 19.48%, 16.79% and 13.46% respectively. CIN2+
was found in the following types most frequently: HPV-16(31.23%),
HPV-33(24.03%), HPV-58(18.41%), HPV-31(11.76%), HPV-18(7.75%), and
HPV-52(7.30%). HPV-16 showed preference for co-infection with HPV-52 and HPV-58.
Conclusion The prevalence of HR-HPV infection based on self-sampling among women
in China exhibited some unique epidemiologic features.
Copyright © 2021. Published by Elsevier Inc.
DOI: 10.1016/j.jclinepi.2021.06.009
PMID: 34161804 [Indexed for MEDLINE]