1. Int J Gynecol Cancer. 1999 Sep;9(5):411-417. doi:
10.1046/j.1525-1438.1999.99055.x.
Prevalence of cervical cancer and feasibility of screening in rural China: a pilot study for the Shanxi Province Cervical Cancer Screening Study.
Belinson J(1), Qiao Y, Pretorius R, Zhang W, Keaton K, Elson P, Fischer C,
Lorincz A, Zahniser D, Wilbur D, Pan Q, Li L, Biscotti C, Dawson A, Li A, Wu L,
Ling Y, Ma CP, Yang XP.
Author information:
(1)Department of Gynecology & Obstetrics, The Cleveland Clinic Foundation,
Cleveland, Ohio;Cancer Institute/Hospital, Chinese Academy of Medical Sciences,
Beijing, People’s Republic of China;Department of Gynecologic Oncology and
Pelvic Surgery, Kaiser Permanente, Fontana, California;Department of
Biostatistics, Cleveland Clinic Foundation, Cleveland, Ohio;Optical Biopsy Tech.
LLC, Knoxville, Tennessee;Digene Corporation, Silver Spring, Maryland;Cytyc
Corporation, Boxborough, Massachusetts;Neopath Inc., Redmond,
Washington;Department of Anatomic Pathology, The Cleveland Clinic Foundation,
Cleveland, Ohio;Cancer Hospital, Yangcheng County, Shanxi Province, People’s
Republic of China; and Women and Children Health Station, Xiangyuan County,
Shanxi Province, People’s Republic of China.
For cervical cancer screening to be feasible in developing countries, it must be
accurate, inexpensive, and easy to administer. We conducted a pilot study in
rural Shanxi Province, People’s Republic of China, to determine disease
prevalence and study feasibility in preparation for a large-scale comparative
trial of 6 screening tests. One-hundred and thirty-six nonpregnant women with no
history of hysterectomy, pelvic radiation, or Papanicolaou tests were screened
in a rural clinic. Ten percent of the women enrolled reported abnormal vaginal
bleeding and 45% reported abnormal vaginal discharge. The tests were the
Papanicolaou test (both conventional and ThinPrep), a self-administered swab
test by Hybrid Capture II for high-risk human papillomavirus (HPV), a test for
high-risk HPV from residual PreservCyt medium, fluorescence spectroscopy, and
visual inspection of the cervix by a clinician. All women also underwent
colposcopy and biopsies as the reference standard. Biopsies showed 12 of 136
women had >/= high-grade squamous intraepithelial lesions (HGSIL). Screening was
completed in 5 half-day sessions, the procedures went smoothly, and local
cooperation was enthusiastic. Disease prevalence in Xiangyuan and Yangcheng
Counties, Shanxi Province, can be estimated at 8.8% (95% CI, 4.5% to 15.0%).
Screening 1000-2000 patients would be sufficient to detect a 10% difference in
accuracy between diagnostic tests. The proposed large-scale trial is feasible.
DOI: 10.1046/j.1525-1438.1999.99055.x
PMID: 11240803
2. Gynecol Oncol. 2001 Nov;83(2):439-44. doi: 10.1006/gyno.2001.6370.
Shanxi Province Cervical Cancer Screening Study: a cross-sectional comparative trial of multiple techniques to detect cervical neoplasia.
Belinson J(1), Qiao YL, Pretorius R, Zhang WH, Elson P, Li L, Pan QJ, Fischer C,
Lorincz A, Zahniser D.
Author information:
(1)Department of Gynecology, The Cleveland Clinic Foundation, Cleveland, Ohio
44195, USA. belinsj@ccf.org
Erratum in
Gynecol Oncol 2002 Feb;84(2):355.
OBJECTIVE: The aim of this study was to design a cervical cancer screening
algorithm for the developing world that is highly sensitive for cervical
intraepithelial neoplasia (CIN) II, III, and cancer and highly specific for CIN
II and III, making it possible to ablate the transformation zone without
histologic confirmation.
METHODS: In rural Shanxi Province, China, we examined 1997 women ages 35-45.
Each subject underwent a self-test for intermediate and high-risk HPV (by HC-II
assay), fluorescence spectroscopy, a liquid-based Pap (read manually and by
computer and used as a direct test for HPV), a visual inspection (VIA)
diagnosis, and colposcopy with multiple cervical biopsies.
RESULTS: Mean age was 39.1 +/- 3.16 years, mean number of births was 2.6 +/-
0.93. Based on tests administered, 4.3% subjects had > or =CIN II. All subjects
with > or =CIN II had either a ThinPrep Pap (> or =ASCUS) or a positive HPV
direct test. The sensitivity and specificity for the detection of > or =CIN II
were, respectively, 83 and 86% for the HPV self-test, 95 and 85% for the HPV
direct test, 94 and 78% for the ThinPrep Pap (> or =ASCUS), 77 and 98% for the
ThinPrep Pap (> or =HGSIL), 94 and 9% for fluorescence spectroscopy, 71 and 74%
for VIA, and 81 and 77% for colposcopy.
CONCLUSION: Based on these data and the existing healthcare infrastructure in
China, we believe that further refinement of primary HPV screening using
centralized labs is indicated. Self-testing in the local villages may be
effective with improvements in the devices and techniques.
Copyright 2001 Academic Press.
DOI: 10.1006/gyno.2001.6370
PMID: 11606114 [Indexed for MEDLINE]
3. Acta Cytol. 2003 Jan-Feb;47(1):45-50. doi: 10.1159/000326474.
A thin-layer, liquid-based pap test for mass screening in an area of China with a high incidence of cervical carcinoma. A cross-sectional, comparative study.
Pan Q(1), Belinson JL, Li L, Pretorius RG, Qiao YL, Zhang WH, Zhang X, Wu LY,
Rong SD, Sun YT.
Author information:
(1)Department of Pathology, Cancer Institute Hospital, Chinese Academy of
Medical Sciences, Peking Union Medical College, Beijing 100021, P.R.C.
OBJECTIVE: To confirm the accuracy of the ThinPrep Pap Test (Cytyc Corp.,
Boxborough, Massachusetts, U.S.A.) on the basis of histologic diagnosis by
biopsy and the detection of human papillomavirus (HPV) DNA in mass screening.
STUDY DESIGN: A total of 1,997 women residing in Xiangyuan County, Shanxi
Province, P.R.C., an area with a high incidence of cervical carcinoma, were
enrolled in this study. We collected exfoliative cervical samples from all
subjects into a liquid buffer (Preserv-Cyt [Cytyc]) and utilized for both
cytologic screening using the ThinPrep Pap Test and HPV DNA testing. Subsequent
colposcopic biopsies were taken on all subjects. All the tests were performed in
an independent and blinded fashion. We compared the ThinPrep Pap test with
colposcopic biopsy and HPV test.
RESULTS: High grade squamous intraepithelial lesions (HSIL) (CIN 2/3) were
identified in 74 (3.7%) of 1,993 women adequately assessed, and there were 12
cases of squamous cell carcinoma (SCC). The false negative rate of ThinPrep
cytology was 3.2% for biopsy-confirmed CIN 3 and 9.3% for CIN 2. Twenty-seven
(87%) of the 31 women with biopsy-confirmed CIN 3 and 12 (100%) of 12 with
biopsy-confirmed SCC had a diagnosis of either HSIL or greater abnormalities on
ThinPrep cytology. In addition, the HPV DNA detection rates offered a good
correlation between cytology and biopsy.
CONCLUSION: The ThinPrep Pap performed extremely well in this primary screening
trial. We found a good correlation between ThinPrep cytology and colposcopic
biopsy on detection of HSIL and SCC; cervical specimens collected in ThinPrep
liquid buffer serve as a direct test for HPV as well.
DOI: 10.1159/000326474
PMID: 12585030 [Indexed for MEDLINE]
4. J Low Genit Tract Dis. 2003 Apr;7(2):107-16. doi:
10.1097/00128360-200304000-00007.
Patient acceptance of self-sampling for human papillomavirus in rural china.
Tisci S(1), Shen YH, Fife D, Huang J, Goycoolea J, Ma CP, Belinson J, Huang RD,
Qiao YL.
Author information:
(1)1University of North Carolina, Chapel Hill, Chapel Hill, NC; 2The Cancer
Institute/Hospital, Chinese Academy of Medical Sciences, Beijing, China;
3Department of Obstetrics and Gynecology, The Cleveland Clinic Foundation,
Cleveland, OH; 4University of Pittsburgh Health System, Pittsburgh, PA;
5Department of Gynecology and Obstetrics, Yangcheng Cancer Hospital, Shanxi
Province, PR, China; and 6Yangchen Cancer Hospital, Shanxi Province, China.
OBJECTIVE.: To test a new survey instrument and determine the acceptance and
potential barriers of cervicovaginal self-sampling for high-risk human
papillomavirus in rural Chinese women. MATERIALS AND METHODS.: Data from
thirteen survey questions assessed acceptance of the self-sampling procedure.
Pain, comprehension, and cultural beliefs were potential barriers evaluated by
the survey. RESULTS.: A total of 1,560 women were surveyed. The average and mode
number of steps of the self-sampling procedure recalled was 5 (out of 7).
Ninety-one percent preferred performing the test at a clinic versus their home.
The major barrier encountered was related to the educational level of the women.
CONCLUSIONS.: The measure performed well in this population. The self-collection
brush was well accepted by these women. Education is the largest hurdle to
overcome in implementing a self-sampling screening program.
DOI: 10.1097/00128360-200304000-00007
PMID: 17051055
5. Ai Zheng. 2003 Oct;22(10):1096-8.
[Value of acetic acid smear test for cervical cancer screening].
[Article in Chinese]
Wu LY(1), Li N, Zhang WH, Li L, Pan QJ, Qiao YL, Rong SD, Zhao FH, Pretorius RG,
Belinson JL.
Author information:
(1)Department of Gynecologic Oncology, Cancer Institute and Hospital, Chinese
Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, PR
China. wlycsco@163bj.com
BACKGROUND & OBJECTIVE: At present, the incidence of cervical cancer is still
high in less developed areas of China; one of the reasons is that cytology in
screening for cervical cancer is not feasible in these areas. The aim of this
study was to analyze the sensitivity and specificity of acetic acid smear test
as a cervical cancer screening test, and evaluate the value of this method for
cervical cancer screening.
METHODS: Acetic acid smear test was performed on 1997 previously unscreened
women aged 35-45 years in Xiangyuan County, Shanxi Province. All women had
cervical cytology, testing for high-risk types of human papillomavirus DNA,
colposcopy, an endocervical curettage and at least five cervical biopsies.
Biopsies were done at the lesions, or one biopsy at 2, 4, 8, 10 o’clock at the
squamocolumnar junction in each normal quadrant.
RESULTS: According to histological diagnosis, 43 women had CIN II, 31 had CIN
III, and 12 had invasive carcinoma. In two women only the endocervix was
positive. Smear test yielded normal results in 1445 women (72.4%), low-grade
squamous intraepithelial lesions (LSILs, CIN I) in 525 (26.3%), high-grade
squamous intraepithelial lesions (HSILs, CIN II- III) in 21 (1.1%), and cancer
in 6 (0.3%). With abnormal visual inspection defined as LSILs or worse, the
sensitivity of acetic acid smear test for HSILs or worse was 70.9% (61 of 86),
the specificity was 74.3% (1420 of 1911). The sensitivity was 64.9% for smaller
lesions (37 of 57), and 88.9% for larger lesions (24 of 27) (P=0.03). The
sensitivity of colposcopy for high-grade SILs or worse was 81.4% (70 of 86), the
specificity was 76.5% (1462 of 1911).
CONCLUSION: This study showed the high specificity and sensitivity of acetic
acid smear test as a primary screening test for cervical cancer. Acetic acid
smear test and colposcopy have similar specificity profiles for CIN II or more
severe lesions. Acetic acid smear test as a primary screening test will be
possible and effective with the benefits of low-cost and simple test in
low-resource settings.
PMID: 14558960 [Indexed for MEDLINE]
6. Int J Gynecol Cancer. 2003 Nov-Dec;13(6):819-26. doi:
10.1111/j.1525-1438.2003.13611.x.
Shanxi Province cervical cancer screening study II: self-sampling for high-risk human papillomavirus compared to direct sampling for human papillomavirus and liquid based cervical cytology.
Belinson JL(1), Qiao YL, Pretorius RG, Zhang WH, Rong SD, Huang MN, Zhao FH, Wu
LY, Ren SD, Huang RD, Washington MF, Pan QJ, Li L, Fife D.
Author information:
(1)Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. belinsj@ccf.org
The objective of this study was to compare the sensitivity and specificity of a
new method for self-sampling for high risk human papillomavirus (HPV) with
direct sampling and liquid based cervical cytology. In Shanxi Province, China,
8,497 women (ages 27-56) underwent a self-sample for HPV using a conical-shaped
brush placed into the upper vagina and rotated. Three to sixteen months later
the women were screened with liquid-based cytology and direct HPV tests.
Subjects with any abnormal test underwent colposcopy and multiple biopsies. Mean
age was 40.9 years. 4.4 percent of subjects had >or=CIN II, 26% a positive
self-sample and 24% a positive direct test for HPV. The sensitivity for
detection of >or=CIN II was 87.5% for self-sampling, and 96.8% for the direct
test (P < 0.001). The specificity was 77.2% for the self-sample and 79.7% for
the direct test. With an abnormal Pap defined as ASCUS or greater the
sensitivity of the Pap for the detection of >CIN II was 88.3% and the
specificity was 81.2%. We conclude that self-sampling for HPV is less sensitive
for >CIN II than the direct test, but similar to liquid based cytology.
DOI: 10.1111/j.1525-1438.2003.13611.x
PMID: 14675319 [Indexed for MEDLINE]
7. Int J Cancer. 2007 Nov 15;121(10):2218-24. doi: 10.1002/ijc.22991.
Inappropriate gold standard bias in cervical cancer screening studies.
Pretorius RG(1), Bao YP, Belinson JL, Burchette RJ, Smith JS, Qiao YL.
Author information:
(1)Department of Obstetrics and Gynecology, S.C.P.M.G.-Fontana, Fontana, CA,
USA. Robert.G.Pretorius@kp.org
As acetic acid-aided visual inspection (VIA) and colposcopic-directed biopsy
miss small >/=cervical intraepithelial neoplasia (CIN) 2, inflation of
sensitivity of VIA may occur when colposcopic-directed biopsy is the gold
standard for >/=CIN 2. To determine whether such inflation occurs, we reviewed
375 women with >/=CIN 2 from the Shanxi Province Cervical Cancer Screening Study
II. These women had positive self or physician-collected tests for high-risk
human papillomavirus or abnormal cervical cytology and had VIA followed by
colposcopy with directed biopsy and endocervical curettage (ECC). If a cervical
quadrant had no lesion, a random biopsy at the squamocolumnar junction within
that quadrant was obtained. Sensitivity of colposcopic-directed biopsy was
higher for >/=CIN 2 involving 3-4 cervical quadrants (81.3%) than for >/=CIN 2
involving 0-2 quadrants (49.0%, p < 0.001). Sensitivities of VIA, cytology of
>/=ASC-US, >/=LSIL, and >/=HSIL were higher for >/=CIN 2 involving 3-4 quadrants
than for >/=CIN 2 involving 0-2 quadrants. When a colposcopic-directed biopsy
gold standard was compared with that of a 5-biopsy standard (which included
>/=CIN 2 from colposcopic-directed biopsy, random biopsy, or ECC), the
sensitivity for >/=CIN 2 of VIA was inflated by 20.0% (65.9% vs. 45.9%, p <
0.001). Sensitivities of other screening tests were not affected. Similar
inflation of sensitivity of VIA was found with an endpoint of >/=CIN 3 (70.4%
vs. 52.0%, p = 0.0013). Inflation of sensitivity of VIA depended upon agreement
between colposcopic-directed biopsy and the screening tests as measured by
kappa. Studies of VIA that used colposcopic-directed biopsy as the gold standard
require reevaluation.
(c) 2007 Wiley-Liss, Inc.
DOI: 10.1002/ijc.22991
PMID: 17657715 [Indexed for MEDLINE]
8. Gynecol Oncol. 2008 Jul;110(1):32-6. doi: 10.1016/j.ygyno.2008.03.003. Epub 2008
May 16.
False negative colposcopy is associated with thinner cervical intraepithelial neoplasia 2 and 3.
Yang B(1), Pretorius RG, Belinson JL, Zhang X, Burchette R, Qiao YL.
Author information:
(1)Department of Pathology, The Cleveland Clinic Foundation, Cleveland, OH
44195, USA.
OBJECTIVE: To assess whether thinner lesion epithelium or lower nuclear density
contribute to false negative colposcopy for dysplasia, we determined epithelial
thickness and nuclear density and correlated this with the accuracy of
colposcopic impression for cervical quadrants with biopsies of normal, CIN 1,
CIN 2 and CIN 3.
METHODS: The thickness and nuclear density of squamous epithelium of 261
selected cervical biopsies (CIN 2/CIN 3, N=144; Normal/CIN 1, N=117) from the
Shanxi Province Cervical Cancer Screening Study (where a colposcopic impression
and biopsy were obtained in each cervical quadrant) were measured. Average
epithelial thickness was defined as the thinnest area plus the thickest area
divided by two. Average nuclear density was defined as the number of nuclei in a
2,500 microm(2) grid at the junction of the superficial and intermediate zones
plus that at the junction of the intermediate and parabasal zones divided by
two. Differences in means were measured by Wilcoxon Rank-Sum Test. Trends among
means were measured by a generalized linear mixed model.
RESULTS: Mean average epithelial thickness for 33 biopsies of CIN 2/CIN 3 from
cervical quadrants with colposcopic impression of normal (184 microm) was less
than that of 111 biopsies of CIN 2/CIN 3 from quadrants with colposcopic
impressions of low, high, or cancer (321 microm, p<.001). CIN 2/CIN 3 had higher
mean average nuclear density (p<.001) and was thinner than normal/CIN 1
(p<.001).
CONCLUSION: The inability of expert colposcopists to visualize some CIN 2/CIN 3
is associated with thinner epithelium.
DOI: 10.1016/j.ygyno.2008.03.003
PMID: 18485462 [Indexed for MEDLINE]
9. Cancer Epidemiol Biomarkers Prev. 2008 Sep;17(9):2350-5. doi:
10.1158/1055-9965.EPI-08-0004.
Descriptive evidence that risk profiles for cervical intraepithelial neoplasia 1, 2, and 3 are unique.
Belinson S(1), Smith JS, Myers E, Olshan A, Belinson J, Pretorius R, Qiao YL,
Hartmann K.
Author information:
(1)Department of Preventive Medicine, Northwestern University, Chicago, IL
60622, USA. s-belinson@northwestern.edu
OBJECTIVE: This study aimed to estimate if risk factor profiles for
histologically confirmed cervical intraepithelial neoplasia (CIN) 2 lesions
differ from those for CIN 1 or 3.
METHODS: A total of 2,055 women positive for high-risk human papillomavirus,
with a minimum of five cervical biopsies, were enrolled in the Shanxi Province
Cervical Cancer Screening Study II. We evaluated risk factor profiles for CIN 2
in comparison with CIN 1 and 3. Polytomous logistic regression was used to
generate odds ratios and corresponding 95% confidence intervals and to test for
differences in odds ratios across histologic grades.
RESULTS: The risk for CIN 3 associated with three or more pregnancies and sexual
intercourse within 4 months of childbirth was higher than that for CIN 2
(P(difference) = 0.02 and 0.0007, respectively). Significant differences in the
associations of age groups with CIN 1 and 2 were observed, such that there were
positive associations with CIN 2 but none for CIN 1. There was no difference in
the association of number of sexual partners or reported number of abortions
between CIN 1 and 2 or between CIN 3 and 2.
CONCLUSIONS: In our study, the patterns of risk factor profiles for CIN 1, 2,
and 3 were unique. Conventional grouping of CIN 2 with 3 for analysis of risk
factors may need revisiting.
DOI: 10.1158/1055-9965.EPI-08-0004
PMID: 18768503 [Indexed for MEDLINE]
10. Int J Cancer. 2006 Jan 15;118(2):442-8. doi: 10.1002/ijc.21327.
Risk factors for HPV infection and cervical cancer among unscreened women in a
high-risk rural area of China.
Zhao FH(1), Forman MR, Belinson J, Shen YH, Graubard BI, Patel AC, Rong SD,
Pretorius RG, Qiao YL.
Author information:
(1)Department of Epidemiology, Cancer Institute/Hospital, Chinese Academy of
Medical Sciences, Beijing, China.
We report a prevalence rate of 23.6% human papillomavirus (HPV) infection with
oncogenic subtypes and 2.4% cervical intraepithelial neoplasia (CIN) III and
cervical cancer (CC) in rural middle-aged women in 2 counties with the highest
CC mortality in Shanxi Province, China. We examined the association of risk
factors to HPV infection and to CIN III and CC in 8,798 unscreened women aged
35-50 years. Multivariate odds ratios (OR) and 95% confidence intervals (CI) for
each endpoint were obtained for risk factors after adjustment for covariates.
The OR of oncogenic HPV were: 1.41 (95% CI = 1.25-1.60) and 1.42 (95% CI =
1.24-1.61) for the participant and her husband having multiple sexual partners,
respectively; 1.67 (95% CI = 1.37-2.04), 1.15 (95% CI = 1.04-1.26), and 0.82
(95% CI = 0.72-0.94) for ever (vs. never) diagnosed with tuberculosis, cervical
inflammation and vaginal trichomoniasis, respectively; while bathing in a public
(v. private) facility had an OR of 1.23 (95% CI =1.11-1.35). Seasonal
fluctuations in HPV infection, but not CC, appeared in Xiangyuan County, with OR
of 1.23 (95% CI = 1.14-1.33) and 1.51 (95% CI = 1.35-1.67) in Spring and Winter
compared to Summer, respectively. The OR of CIN III and CC in the HPV positives
were: 2.03 (95% CI = 1.63-2.53) for ages > or =45 years (vs. <40); and 4.01 (95%
CI = 1.46-11.0) for > or =3 (vs. no) home births. Public health interventions
and control strategies for improving the reproductive health of women in these
rural populations need to be developed to reduce risk of HPV and subsequent CC.
Copyright 2005 Wiley-Liss, Inc.
DOI: 10.1002/ijc.21327
PMID: 16080192 [Indexed for MEDLINE]
11. Int J Cancer. 2012 Sep 15;131(6):1388-95. doi: 10.1002/ijc.27367. Epub 2012 Jan
27.
Population-based human papillomavirus 16, 18, 6 and 11 DNA positivity and seropositivity in Chinese women.
Smith JS(1), Lewkowitz AK, Qiao YL, Ji J, Hu S, Chen W, Zhang R, Liaw KL, Esser
M, Taddeo FJ, Pretorius RG, Belinson JL.
Author information:
(1)Department of Epidemiology, Gillings School of Global Public Health, Chapel
Hill, NC 27599, USA. JenniferS@unc.edu
To optimize HPV vaccination implementation at the population-level in China,
data are needed on age-specific HPV 16, 18, 6 and 11 prevalence. This
cross-sectional, population-based study evaluated the age- and type-specific HPV
16, 18, 6 and 11 prevalence of DNA and serum antibodies among women in China.
From July 2006 to April 2007, 17-54 year old women from three rural provinces
(Xinjiang, Shanxi and Henan) and two cities (Beijing and Shanghai) provided
cervical exfoliated cells for HPV DNA and liquid-based cervical cytology
(SurePath). High- and low-risk HPV types were detected with HC-II (Qiagen), with
genotyping of HPV-positive samples using Linear Array (Roche). HPV 16, 18, 6 and
11 serum antibodies were detected using a Luminex-based, competitive immunoassay
(Merck). A total of 4,206 women with DNA and serum antibody results were
included. HPV 16 DNA prevalence peaked in women aged 30-34 (4.2%) and 45-49 yr
(3.8%), while HPV 18 DNA prevalence peaked at ages 40-44 yr (1.3%). Most women
were dually DNA and serum antibody negative: HPV 16 (92.2%), 18 (97.2%), HPV 16
and 18 (90.2%), 6 (92.0%), 11 (96.6%), 6 and 11(89.9%) and HPV 16, 18, 6 and 11
(82.5%). Future national HPV vaccination programs in China should target younger
women due to increased exposure to HPV types 16, 18, 6 and 11 with increasing
age. Cumulative exposure of HPV may be underreported in this population, as
cross-sectional data do not accurately reflect exposure to HPV infections over
time.
Copyright © 2011 UICC.
DOI: 10.1002/ijc.27367
PMCID: PMC4446973
PMID: 22120998 [Indexed for MEDLINE]
12. Cancer Causes Control. 2013 Apr;24(4):795-803. doi: 10.1007/s10552-013-0162-8.
Epub 2013 Feb 9.
Prevalence of type-specific human papillomavirus and pap results in Chinese women: a multi-center, population-based cross-sectional study.
Wu EQ(1), Liu B, Cui JF, Chen W, Wang JB, Lu L, Niyazi M, Zhao C, Ren SD, Li CQ,
Gong XZ, Smith JS, Belinson JL, Liaw KL, Velicer C, Qiao YL.
Author information:
(1)Department of Cancer Epidemiology, Cancer Institute and Hospital, Chinese
Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
PURPOSE: To estimate the burden of human papillomavirus (HPV) infection among
sexually active women in China.
METHODS: We conducted a multi-center, population-based study between May 2006
and April 2007. A total of 4,215 women aged 17-54 years were surveyed from five
geographical sites: Beijing, Shanghai, Shanxi, Henan, and Xinjiang. Direct
endocervical exfoliated cells were collected from consenting participants for
Sure Path liquid-based cytology (BD) and HPV testing. HPV testing was performed
with Hybrid Capture II (Qiagen) with high-risk and low-risk probes, and Linear
Array (Roche) was utilized for HPV genotyping.
RESULTS: Approximately 11 % of the study population had a cytological
abnormality (ASCUS or worse). HPV prevalence in the entire study population was
14.3 % (age-standardized to the world standard female population 14.5 %). The
most prevalent types found were HPV16 (2.9 %), HPV52 (1.7 %), HPV58 (1.5 %),
HPV33 (1 %), and HPV18 (0.8 %). Patterns of HPV prevalence differed by age,
geographic region, and cytology findings. However, HPV16 was predominant among
all grades of cytological abnormalities for all areas.
CONCLUSIONS: Although HPV18 appeared to be less frequent among population-based
samples of China, given the high prevalence of HPV 16 and 18 in high-grade
squamous intraepithelial lesion (HSIL) or worse pap abnormalities, prophylactic
HPV16/18 vaccines should substantially reduce the burden of cervical cancer in
China.
DOI: 10.1007/s10552-013-0162-8
PMID: 23397310 [Indexed for MEDLINE]
13. Int J Gynecol Cancer. 2013 May;23(4):716-23. doi: 10.1097/IGC.0b013e318286a95d.
Six-year regression and progression of cervical lesions of different human papillomavirus viral loads in varied histological diagnoses.
Wang SM(1), Colombara D, Shi JF, Zhao FH, Li J, Chen F, Chen W, Li SM, Zhang X,
Pan QJ, Belinson JL, Smith JS, Qiao YL.
Author information:
(1)Department of Cancer Epidemiology, Cancer Institute/Hospital, Chinese Academy
of Medical Sciences and Peking Union Medical College, Seattle, WA, USA.
OBJECTIVE: This study aims to evaluate human papillomavirus (HPV) viral loads as
a biomarker for triage into colposcopy and cervical intraepithelial neoplasia
grade 2 (CIN2) therapy to reduce the colposcopy referral rate and CIN2
overtreatment in low-resource settings.
METHODS: In 1999, 1997 women aged 35 to 45 years in Shanxi, China, received 6
cervical screenings with pathological confirmation. In 2005, 1461 histologically
normal women, 99 with CIN grade 1 (CIN1), and 30 with CIN2 or worse (CIN2+) were
rescreened in a follow-up study. Human papillomavirus was detected by Hybrid
Capture 2. Viral load, estimated by the ratio of relative light units to
standard positive control (RLU/PC), was categorized into 4 groups: negative
(<1.0), low (≥1.0, <10.0), moderate (≥10.0, <100.0), and high (≥100.0). We
estimated the cumulative incidence of CIN2+ by viral load subgroups and
calculated adjusted hazard ratios for CIN2+ using Cox proportional hazards
regression.
RESULTS: Cumulative incidence of CIN2+ increased with baseline HPV viral loads
among normal women and women with CIN1 at baseline (P(-trend) < 0.001). Repeat
moderate-high viral load was associated with the highest risk for CIN2+
(adjusted hazard ratio, 188.8; 95% confidence interval, 41.2-864.1). Raising the
ratio of relative light units to standard positive control cutoff from 1.0 to
10.0 for colposcopy greatly reduced the referral rate from 18.1% to 12.9%. It
also increased the specificity (84.8% vs 90.4%), the positive predictive value
(22.5% vs 28.9%), and the positive likelihood ratio (6.4 vs 8.9), yet with loss
of sensitivity by 12% (97.6% vs 85.7%). Among women with CIN2 at baseline, 56%
regressed to normal, 24% regressed to CIN1, 4% remained CIN2, and 16% progressed
to CIN grade 3 or worse.
CONCLUSIONS: Locales using HPV testing as the primary screening method and
lacking high-quality cytology-based screening should consider viral load as an
alternative to colposcopy triage for women older than 35 years. Viral loads may
also predict CIN2 progression until additional biomarkers become available.
DOI: 10.1097/IGC.0b013e318286a95d
PMCID: PMC3636161
PMID: 23455757 [Indexed for MEDLINE]
Conflict of interest statement: Disclosure Statement All authors declare that
they have no conflicts of interest.
14. Cancer Epidemiol. 2013 Dec;37(6):939-45. doi: 10.1016/j.canep.2013.10.005. Epub
2013 Nov 8.
Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grades 1 or worse among 4215 Chinese women in a population-based study.
Zhang R(1), Velicer C, Chen W, Liaw KL, Wu EQ, Liu B, Cui JF, Belinson JL, Zhang
X, Shen GH, Chen F, Qiao YL.
Author information:
(1)Department of Cancer Epidemiology, Cancer Hospital and Institute, Chinese
Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
PURPOSE: To estimate the burden of human papillomavirus (HPV) infection and
cervical disease among sexually active women in a sample of Chinese women.
METHODS: A multicenter, population-based study was conducted between May 2006
and April 2007. A total of 4215 sexually active women aged 17-54 years were
surveyed from five geographical sites representing both urban and rural areas:
Beijing, Shanghai, Shanxi, Henan and Xinjiang. Women were referred for
colposcopy on the basis of results of Pap testing and HPV screening. HPV
genotyping of the CIN1+ specimens was performed with INNO-LiPA. Attribution of
HPV types to lesions was estimated using a fractional contribution approach.
RESULTS: 13.3% of the women (559/4215) were referred for colposcopy; 4.3%
(183/4215) of these were diagnosed with CIN1+. Of the latter, 88.5% (162/183)
were typed and 94.4% (153/162) were HPV-positive. HPV16 was the most prevalent
type in lesions in both urban and rural settings. Combined, HPV16 and 18 were
attributable to 71.4% of HPV-positive CIN2+ lesions. In addition, HPV31, 33, 52
and 58 were prevalent in CIN1+ lesions, with HPV33, 52, and 58 combined
accounting for 24.1% CIN2+ lesions. Though prevalent, HPV31 always occurred as a
co-infection with another HPV type and therefore was attributed minimal
causality.
CONCLUSIONS: HPV16 and 18 are associated with the majority of cervical lesions
in Chinese women from which this population-based sample was drawn. In addition,
other HPV types, such as 33, 52, and 58, also play an important role in cervical
disease.
Copyright © 2013. Published by Elsevier Ltd.
DOI: 10.1016/j.canep.2013.10.005
PMID: 24210584 [Indexed for MEDLINE]
15. Case Rep Womens Health. 2018 Mar 10;17:11-13. doi: 10.1016/j.crwh.2018.02.002.
16. 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]
17. J Low Genit Tract Dis. 2020 Jul;24(3):243-246. doi:
10.1097/LGT.0000000000000546.
Evaluation of Liquid Versus Dry Specimen Transport With a Newly Validated Isothermal Amplification High-Risk Human Papillomavirus Assay.
Sun J(1), Wu S(1), Hu L(1), Shang H(1), Yang Y(1), Pretorius R(2), Huang Y(1),
Yang X(1), Wu X(1), Belinson J.
Author information:
(1)Department of Obstetrics and Gynecology, Shanxi Bethune Hospital & Shanxi
Academy of Medical Sciences, Taiyuan, Shanxi Province, China.
(2)Department of Obstetrics and Gynecology, Southern California Permanente
Medical Group, Fontana, CA.
OBJECTIVE: The aim of the study was to determine whether the proportion of
positive high-risk human papillomavirus (HR-HPV) tests in endocervical specimens
transported dry differs from paired specimens transported in liquid media.
METHODS: Five hundred women aged of 30 to 55 years were recruited, Shanxi
Bethune Hospital, China. Two samples were collected from the endocervix per
patient, one placed into empty vial, the other into a liquid transport solution.
All samples were analyzed by AmpFire HR-HPV assay.
RESULTS: Total 1,000 samples collected from 500 patients were analyzed by the
AmpFire HR-HPV assay. The total invalid rate was 0.2% (2/1,000). The proportion
of endocervical samples testing positive for HR-HPV transported dry (42.2%,
210/498 [95% CI = 37.8%-46.6%]) was similar to the proportion of paired
endocervical samples testing positive transported in liquid media (40.4%,
201/498 [95% CI = 36.0%-44.8%], p = .18 [McNemar test]). That the 2 transport
methods are likely measuring the same positive (and negative) specimens is
suggested by the finding that κ value for the correlation of positive HR-HPV in
endocervical specimens transported dry with those transported in liquid media
was 0.86 (95% CI = 0.81-0.90).
CONCLUSIONS: Endocervical specimens transported dry have similar proportion of
positive HR-HPV tests as those transported in liquid media. Dry brush transport
of endocervical samples paired with the special characteristics of AmpFire
HR-HPV may become an important addition to population based cervical cancer
screening.
DOI: 10.1097/LGT.0000000000000546
PMID: 32569253 [Indexed for MEDLINE]