Analysis on cancer incidence and mortality attributed to human papillomavirus infection in China, 2016 / 中华流行病学杂志

Objective: We aim to evaluate the morbidity and mortality of cancer attributable to human papillomavirus (HPV) infection in China in 2016. Methods: Based on the cancer incidence and mortality rates, national population data, and population attributable fraction (PAF) in China, we calculated the number of incidence and death cases attributed to HPV infection in different areas, age groups, and gender in China in 2016. The standardized incidence and mortality rates for cancer attributed to HPV infection were calculated by using Segi's population. Results: In 2016, a total of 124 772 new cancer cases (6.32 per 100 000) were attributed to HPV infection in China, including 117 118 cases in women and 7 654 cases in men. Of these cancers, cervical cancer was the most common one, followed by anal cancer, oropharyngeal cancer, penile cancer, vaginal cancer, laryngeal cancer, oral cancer, and vulvar cancer. A total of 41 282 (2.03 per 100 000) deaths were attributed to HPV infection, of which 37 417 occurred in women and 3 865 in men. Most deaths were caused by cervical cancer, followed by anal cancer, oropharyngeal cancer, penile cancer, laryngeal cancer, vaginal cancer, oral cancer, and vulvar cancer. The incidence and mortality rates of cervical cancer increased rapidly with age, peaked in age group 50-54 years, then decreased obviously. The morbidity and mortality rates of non-cervical cancer increased with age. The cancer case and death numbers in rural areas (57 089 cases and 19 485 deaths) were lower than those in urban areas (67 683 cases and 21 797 deaths). However, the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of cervical cancer were higher in rural areas than in urban areas. There were no significant differences in ASIR and ASMR of non-cervical cancers between urban areas and rural areas. Conclusions: The incidence of cancers attributed to HPV infection in China was lower than the global average, but the number of incidences accounted largely, furthermore there is an increasing trend of morbidity and mortality. The preventions and controls of cervical cancer and male anal cancer are essential to contain the increases in cancer cases and deaths attributed to HPV infection.

Performance of point-of-care testing for cervical cancer screening / 中华预防医学杂志

Objective: To evaluate the performance of point-of-care testing for cervical cancer and precancerous lesions screening. Methods: In September 2020, 197 and 273 women were selected by using simple random sampling method from "self-sampling" cohort and "physician-sampling" cohort established in Xiangyuan county, Shanxi Province, China, respectively. Cervical exfoliated cells were collected by women themselves or gynecologists. All samples were detected by POCT and women with positive result were directly referred for colposcopy. Subsequently, all the samples were detected by careHPV and PCR test. Colposcopy and punch biopsy were performed for women with POCT negative but careHPV or PCR test positive at another visit. Using histopathological diagnosis as the gold standard, we calculated sensitivity, specificity and drew the receiver operating characteristic (ROC) curves. The accuracy of POCT was analyzed and compared to that of careHPV and conventional PCR test in cervical cancer and precancerous lesions screening. Results: The median (Q1 , Q3) age of 470 women was 51 (45, 57) years old. Based on self-sampling, the sensitivity and specificity of POCT for CIN2+ were 100.00% (95%CI: 56.56%-100.00%) and 28.95% (95%CI: 22.97%-35.76%), respectively. Compared with POCT, POCT HPV16/18 test had similar sensitivity and higher specificity of 89.47% (95%CI: 84.30%-93.08%). Self-sampling POCT HPV16/18 test had an AUC of 0.947 (95%CI:0.910-0.985), which was higher than that of careHPV and PCR test. Physician-sampling POCT test had 100.00% sensitivity (95%CI: 64.57%-100.00%) and 55.85% specificity (95%CI: 49.83%-61.70%) for detecting CIN2+. POCT HPV16/18 test had lower sensitivity (71.43%, 95%CI: 35.90%-91.76%) and higher specificity (92.45%, 95%CI: 88.63%-95.06%). POCT HPV16/18 test generally showed similar AUC on both self-collected samples and clinician-collected samples (0.947 vs 0.819, P=0.217). Conclusion: POCT HPV16/18 test is an effective method with relatively high sensitivity and specificity for cervical cancer screening.

Topical Delivery of Modified Da-Cheng-Qi Decoction () Using Low-Frequency Ultrasound Sonophoresis for Refractory Metastatic Malignant Bowel Obstruction: An Open-Label Single-Arm Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of topical delivery of modified Da-Cheng- Qi Decoction (, MDCQD) by low-frequency ultrasound sonophoresis (LFUS) in patients with refractory metastatic malignant bowel obstruction (MBO) using an objective performance criteria (OPC) design.@*METHODS@#Fifty patients with refractory metastatic MBO were enrolled in this open-label single-arm clinical trial. Alongside fasting, gastrointestinal decompression, glycerol enema, intravenous nutrition and antisecretory therapy, a 50 g dose of MDCQD (prepared as a hydrogel) was applied through topical delivery at the site of abodminal pain or Tianshu (S 25) using LFUS for 30 min, twice daily for 5 consecutive days. The overall outcome was the remission of intestinal obstruction, and improvement on abdominal pain, abdominal distention, nausea and vomiting scores. Indicators of safety evaluation included liver and renal function as well as blood coagulation indicators.@*RESULTS@#Among 50 patients, 5 patients (10%) showed complete remission of intestinal obstruction and 21 patients (42%) showed improvement of intestinal obstruction. The overall remission rate of bowel obstruction was 52%. The results of the symptom score, based on the severity and frequency of the episode, are as follows: 26 patients (52%) showed improvment on symptom scores, 20 patients (40%) did not respond to treatment, and 4 patients (8%) discontinued treatment due to intolerance. No serious adverse effects or abnormal changes on liver and renal function or blood coagulation were observed.@*CONCLUSION@#Topical delivery of MDCQD at 100 g/day using LFUS can improve the treatment response in patients with refractory metastatic MBO.

Role of active and passive smoking in high-risk human papillomavirus infection and cervical intraepithelial neoplasia grade 2 or worse / 부인종양

OBJECTIVE: We performed a pooled analysis to examine cigarette smoking and household passive smoke exposure in relation to the risk of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia grade 2+ (CIN2+). METHODS: Data were pooled from 12 cross-sectional studies for cervical cancer screenings from 10 provinces of China in 1999–2007. A total of 16,422 women were analyzed, along with 2,392 high-risk-HPV (hr-HPV) positive women and 381 CIN2+ cases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models controlling for sexual and non-sexual confounding factors. RESULTS: There was an excess risk between active smoking and hr-HPV infection and CIN2+. Adjusted OR for ever smokers vs. never smokers was 1.45 (95% CI=1.10–1.91), for hr-HPV infection and 1.89 (95% CI=1.03–3.44), for CIN2+. Passive smoking had a slightly increased risk on the hr-HPV infection with adjusted OR 1.11 (1.00–1.24), but no statistical association was observed between passive smoke exposure and CIN2+. Compared with the neither active nor passive smokers, both active and passive smokers had a 1.57-fold (95% CI=1.14–2.15) increased risk of HPV infection and a 1.99-fold (95% CI=1.02–3.88) risk of CIN2+. CONCLUSION: Our large multi-center cross-sectional study found active smoking could increase the risk of overall hr-HPV infection and CIN2+ adjusted by passive smoking and other factors. Passive smoking mildly increased the risk of HPV infection but not the CIN2+. An interaction existed between passive tobacco exposure and active smoking for hr-HPV infection and the CIN2+.

High-risk human papillomavirus genotype distribution and attribution to cervical cancer and precancerous lesions in a rural Chinese population / 부인종양

OBJECTIVE: To explore the genotype distribution of high-risk human papillomavirus (HR-HPV) and its attribution to different grades of cervical lesions in rural China, which will contribute to type-specific HPV screening tests and the development of new polyvalent HPV vaccines among the Chinese population. METHODS: One thousand two hundred ninety-two subjects were followed based on the Shanxi Province Cervical Cancer Screening Study I (SPOCCS-I), and screened by HPV DNA testing (hybrid capture® 2 [HC2]), liquid-based cytology (LBC), and if necessary, directed or random colposcopy-guided quadrant biopsies. HPV genotyping with linear inverse probe hybridization (SPF10-PCR-LiPA) was performed in HC2 positive specimens. Attribution of specific HR-HPV type to different grades of cervical lesions was estimated using a fractional contribution approach. RESULTS: After excluding incomplete data, 1,274 women were included in the final statistical analysis. Fifteen point two percent (194/1,274) of women were HR-HPV positive for any of 13 HR-HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and the most common HR-HPV types were HPV16 (19.1%) and HPV52 (16.5%). The genotypes most frequently detected in HR-HPV-positive cervical intraepithelial neoplasia grade 1 (CIN1) were HPV52 (24.1%), HPV31 (20.7%), HPV16 (13.8%), HPV33 (13.8%), HPV39 (10.3%), and HPV56 (10.3%); in HR-HPV-positive cervical intraepithelial neoplasia grade 2 or worse (CIN2+): HPV16 (53.1%), HPV58 (15.6%), HPV33 (12.5%), HPV51 (9.4%), and HPV52 (6.3%). HPV52, 31, 16, 33, 39, and 56 together contributed to 89.7% of HR-HPV-positive CIN1, and HPV16, 33, 58, 51, and 52 together contributed to 87.5% of CIN2+. CONCLUSION: In summary, we found substantial differences in prevalence and attribution of CINs between different oncogenic HPV types in a rural Chinese population, especially for HPV16, 31, 33, 52, and 58. These differences may be relevant for both clinical management and the design of preventive strategies.

Trend analysis of cervical cancer incidence and mortality rates in Chinese women during 1989-2008 / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the trend of cervical cancer incidence and mortality rates during 1989-2008 in Chinese women, so as to inform the development of relevant policies and strategies in China.</p><p><b>METHODS</b>The incidence and mortality rates of cervical cancer during 1989-2008 in urban and rural areas were calculated based on the data from the National Cancer Registry Database. Age-standardized rates were calculated using the Chinese population of 1982 and World Segi's population of 1985. Joinpoint regression analysis was performed to obtain annual percentage changes (APC) so as to assess the trend of incidence and mortality rates over the period from 1989 to 2008.</p><p><b>RESULTS</b>The crude incidence rate of cervical cancer in Chinese women increased from 3.06/10(5) in 1989-1990 to 11.87/10(5) in 2007-2008 (from 4.96/10(5) to 11.98/10(5) in urban registration areas and from 2.39/10(5) to 11.77/10(5) in rural registration areas).The crude mortality rate slightly increased from 2.19/10(5) in 1989-1990 to 3.20/10(5) in 2007-2008 (from 3.21/10(5) to 2.56/10(5) in urban registration areas and from 1.82/10(5) to 3.75/10(5) in rural registration areas). Generally, the upward trends of crude incidence rates were shown over the year 1989-2008, with an APC of 14.4% after 1997 in urban areas and 22.5% after 1999 in rural areas.After age standardization of world population, the APC of incidence rates in recent decade in urban areas remained stable, and the one in rural areas slightly decreased.Although the overall crude and world age-standardized mortality rates had no significant changes during 1989-2008, the crude mortality rates increased by 8.1% annually after 1999.The upward trends were also shown for crude and world age-standardized mortality rates in urban areas after 2001 with an APC of 7.3%.The crude mortality rates in rural areas increased by 3.9% annually during 1989-2008, but no significant change was found after age standardization.</p><p><b>CONCLUSIONS</b>Over the last decade, the cervical cancer incidence and mortality rates ascended by year in China. It is particularly urgent to establish a comprehensive prevention and control system that combines cervical cancer screening and human papillomavirus vaccination, so as to reduce the burden of cervical cancer in Chinese women.</p>

Cost-effectiveness analysis on the once-in-a-lifetime cervical cancer screening program for women living in rural and urban areas of China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To estimate the cost-effectiveness of once-in-a-lifetime cervical cancer screening program and to predict the optimal modality for its operation on women living in rural and urban areas of China, based on Markov modeling and simulation.</p><p><b>METHODS</b>Three modalities including visual inspection with acetic acid plus Lugol's iodine (VIA/VILI), conventional Pap Smear (Pap Smear), and simple HPV DNA testing (careHPV) were hypothesized for the rural cohort, whereas other five modalities including Pap Smear, liquid-based cytology (LBC), simple HPV DNA testing (careHPV), Hybrid Capture 2 HPV DNA testing (HC2), and LBC plus HC2 (LBC + HC2) were tested for the urban cohort. A Markov model was constructed based on the factors as natural history, screening, diagnosis and treatment on cervical cancer using data related to the epidemics and the costs from rural and urban areas of the country. Long-term effectiveness and cost-effectiveness were predicted through simulation of the model.</p><p><b>RESULTS</b>Compared to the non-screening scenario, the amount of life years saved were 277.97 - 2727.53 and 134.02 - 1446.84 years per 100 000 women, respectively, for different cohorts in rural and urban areas. The cost-effectiveness ratios were 1520.99 - 2453.74 and 3847.35 - 44 570.35 RMB per life year saved, respectively, for different cohorts in rural and urban areas. The incremental cost-effective ratio for careHPV starting from 40 years old (careHPV@40) and careHPV from 30 years old (careHPV@30) dominated other strategies for the rural cohort, while careHPV@40, careHPV@30, HC2 from 30 years old (HC2@30), and LBC + HC2 from 30 years old (LBC + HC2@30) were dominant for the urban cohort.</p><p><b>CONCLUSION</b>All eight once-in-a-lifetime cervical cancer screening modalities were cost-effective based on our model. In particular, careHPV screening starting from 40 years old seemed to be the most cost-effective one for women living in both rural and urban areas.</p>

Incidence and mortality of oral and pharyngeal cancers in China, 2003 to 2007 / 中华流行病学杂志

Objective To analyze the incidence and mortality of oral and pharyngeal cancers from 32 cancer registration centers,2003 to 2007.Methods Data from 32 eligible cancer registries were included in this study.Both crude and age-standardized incidence and mortality of oral and pharyngeal cancers from 2003 to 2007 were calculated and stratified by area and gender.Age-stratified incidence and mortality,as well as the proportions of new and death cases of oral and pharyngeal cancer were also calculated at each site.Results Mouth,tongue and salivary gland were the most predilcction sitcs of oral and pharyngeal cancers.The crude incidence for both oral and pharyngeal cancers was 3.15/105 from 2003 to 2007.The age-standardized incidence rates using the Chinese population (1982) and the World Segi' s population were 1.75/105 and 2.26/105.The crude mortality of oral and pharyngeal cancer was 1.37/105 from 2003 to 2007; with age-standardized mortality rates,using the Chinese population (1982) and the World Segi' s population were 0.69/105 and 0.94/105.Both incidence and mortality were higher in males than in females,higher in urban than in rural areas,and ascended with age.Age-standardized incidence and mortality in Zhongshan city ranked first among all the cancer registration areas.Age-standardized incidences by gender and area increased slightly from 2003 to 2007,while age-standardized mortalities were stable.Conclusion Although the incidence and mortality of oral and pharyngeal cancer were low in China from 2003 to 2007,attention should also be paid since the exposure of relative risk factors did not seem to have reduced and the incidence increased slightly.

Comparison on the predictive values of four screening methods regarding cervical cancer / 中华流行病学杂志

To compare the predictive values of 5% acetic acid stain and visual inspection, human papillomavirus (HPV) Self test, ThinPrep Pap and HPV direct test in screening for cervical cancer with biopsy as gold standard. Positive predictive values and negative predictive values were compared simultaneously by joint hypothesis tests and then either positive predictive values or negative predictive values of the any two screening tests were compared by marginal regression based on both GEE and weighted least square methods. Hochberg method was used for multiplicity adjustment. It was showed that HPV direct test had the highest negative predictive value and ThinPrep Pap the highest positive predictive value. 5% acetic acid stain and visual inspection had both the lowest positive predictive value and negative predictive value. Both HPV direct test and ThinPrep Pap were efficient, but the latter required compatible infrastructure and skilled caregivers to go with. Both 5% acetic acid stain and visual inspection were inexpensive, and their positive predictive value and negative predictive value were lower than HPV self-test. They also had similar positive predictive value with HPV direct test and similar negative predictive value with ThinPrep Pap. HPV self-test appeared to be efficient, suggesting that it had significant potential for screening program to be implemented in the rural areas of China since the test could be performed without speculum examination in low-resource regions.

Effectiveness and health economic analysis of strategies on cervical cancer screening and early diagnosis and treatment / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the appropriate strategies which are suitable for the areas with diverse health and economic resource settings in China by estimating the life outcomes and cost-effectiveness of several cervical cancer screening strategies.</p><p><b>METHODS</b>Markov model was used to calculate the long-term effectiveness, utility, benefit and cost among screened and unscreened cohorts in rural and urban areas, and then analyses of cost-effectiveness, cost-utility and cost-benefit were performed. The assessed screening strategies were acetic acid of visual inspection combined with Lugol's iodine staining (VIA/VILI), conventional Pap smear and simple HPV DNA testing (careHPV) in rural areas, and conventional Pap smear, simple HPV DNA testing (careHPV), HPV DNA testing (HC2) and liquid-based cytology (LBC) alone or combined with HPV DNA testing (LBC+HC2) in urban areas. We estimated the life outcomes and cost-effectiveness of the above screening strategies at one-year, 3-year and 5-year intervals.</p><p><b>RESULTS</b>All of the screening strategies were effective to decrease cervical cancer mortality and to increase life years, with a trend of shorter screening interval having better effectiveness. However, no matter in urban or rural areas, compared with careHPV testing at 5-year interval, the costs of other screening strategies were 1.28 - 13.86 folds, 1.31 - 14.14 folds, and 1.27 - 12.80 folds higher to avoid one death, to save a year of life, and a QALY, and the benefit per cost of other screening strategies was 9.9%-90.2%.</p><p><b>CONCLUSIONS</b>careHPV testing at 5-year interval has the best cost-effectiveness performance and the highest benefit-cost ratio with the moderate life outcomes. It is the optimal cervical cancer screening strategy to be generalized in our country. careHPV testing at 3 years interval can be considered in more developed areas to achieve better effectiveness.</p>

Three-year follow-up results of visual inspection with acetic acid/Lugol's iodine (VIA/VILI) used as an alternative screening method for cervical cancer in rural areas / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>In China, there has been no established national program for cervical cancer prevention, the screening methods and experiences are especially deficient in the rural areas. The aim of this paper is to evaluate the effects of acetic acid/Lugol's iodine (VIA/VILI) used for screening of cervical cancer and pre-cancerous lesions in a rural area of China by analyzing the large-scale population-based screening data from the demonstration site.</p><p><b>METHODS</b>Women aged 30-59 years from Xiangyuan County in Shanxi Province were recruited for cervical cancer screening from 2005 to 2007. VIA/VILI was the primary screening method followed by colposcopy if the VIA/VILI was positive. Cervical lesions were diagnosed by directed biopsy under the colposcopy. The VIA/VILI negative women or cervical intraepithelial neoplasia 1 (CIN1) were re-screened using the same procedure in the next year.</p><p><b>RESULTS</b>In total, 7145 women received the cervical cancer screening, with a participation rate of 74.75%. Their average age was 42.16 years. A total of 1287 women were consecutively screened for three times from 2005 to 2007. The detection rates of CIN2, CIN3 and cervical cancer were 0.70% (9/1287), 1.01% (13/1287) and 0.23% (3/1287) for the first round screening, and were 0.22% (2/976), 0.11% (1/976) and 0% (0/976) for the second round screening, respectively. Only one CIN2 was found in the third round screening. In the years of 2006-2007, 3490 women were screened consecutively twice. The detection rates of CIN2, CIN3 and cervical cancer were 0.26% (9/3490), 0.52% (18/3490) and 0.15% (5/3490) for the first round screening, and 0.40% (14/2943), 0.40% (14/2943) and 0.03% (1/2943) for the second round screening. Likewise, 2 368 women were screened consecutively twice in the years of 2007-2008. The detection rates of CIN2, CIN3 and cervical cancer were 0.55% (13/2368), 0.25% (6/2368) and 0.12% (3/2368) for the first round screening, and 0.42 (10/2040), 0.04% (1/2040) and 0% for the second round screening. The cumulative detection rates for CIN2, CIN3 and cervical cancer were 0.81% (58/7145), 0.74% (53/7145) and 0.17% (12/7145), respectively. And 53.45% (31/58) of CIN2, 68.81% (37/53) of CIN3 and almost all cervical cancers (11/12) were found during the first round screening, except for an early stage cervical cancer (Ia). Only one CIN2 was detected in the third round screening in the same population. The average age of CIN1, CIN2, CIN3 and cervical cancer were 38.65, 40.61, 44.10 and 46.73 years, respectively.</p><p><b>CONCLUSIONS</b>VIA/VILI can be used as an alternative screening method for cervical cancer and high-grade pre-cancerous lesions among the women aged 30-59 years in China's rural areas because of its low cost, easy training for the local health providers, and less depending on facilities. One round screening by VIA/VILI can detect more than a half of CIN2, two-thirds of CIN3 and almost all the cervical cancer in the population, and the detection rates of CIN2/3 can be increased by two consecutive rounds of screening.</p>

Cervical cancer mortality in 2004 - 2005 and changes during last 30 years in China / 中华预防医学杂志

<p><b>OBJECTIVE</b>To analyze the cervical cancer mortality and distribution profiles by areas and population in 2004 - 2005 and the changes in the last 30 years.</p><p><b>METHODS</b>The demographic information and cervical cancer death data came from the Third National Retrospective Sampling Survey of Death Causes which including 158 sampling areas (including 61 cities and 97 villages; 52 in the east region, 49 in the middle region and 57 in the west region) covered 31 province-level regions in the interior of China by multiple stage stratified clustering sampling. The total number of the samples were 142 660 482 person years (72 970 241 person years in male and 69 690 241 person years in female). The crude and age-specific death rate was calculated. The standardized death rate was calculated by using 5 years interval from the census data of 2000. In addition, the mortality data was compared with the two previous national death surveys in 1970's and 1990's, respectively.</p><p><b>RESULTS</b>In the sampling region of the third retrospective death causes survey from 2004 to 2005, the crude death rate of cervical cancer was 2.86/100 000 (1995/69 690 241), which accounting for 2.86% (1995/69 667) and ranking 9th of all cancer death causes in female population. The crude death rates of cervical cancer were 2.88/100 000 (1326/46 091 419) and 2.83/100 000 (669/23 598 822) for rural areas and urban areas, respectively, the Chinese population adjusted death rates of rural and urban areas were 2.01/100 000 and 1.67/100 000, respectively. The standardized death rates of cervical cancer in 1973 - 1975 and 1990 - 1992 were 11.10/100 000 and 3.25/100 000, respectively, which accounting for 17.91% and 4.86%, respectively; in 2004 - 2005, the crude death rates increased by age, rose remarkably from the age of 40 and arrived the peak of 20.83/100 000 (82/393 624) at the age of 85. The mortality among 35 - 44 year-old group was higher than those in 1990's. The crude death rates of the middle, west and east areas were 3.41/100 000 (827/24 225 738), 3.25/100 000 (636/19 563 647) and 2.05/100 000 (532/25 900 856), respectively, the Chinese population adjusted death rates of the middle and west areas were about twice that of the east (2.35/100 000 in the middle, 2.38/100 000 in the west, and 1.19/100 000 in the east).</p><p><b>CONCLUSION</b>The mortality of cervical cancer was higher in rural areas than that in urban, as well as higher in the middle and west areas than that in east area in the interior of China in 2004 - 2005. Younger trend of cervical cancer death was observed; the mortality of cervical cancer and constituent ratio in the female tumor death continued to decline compared to those in 1973 - 1975 and 1990 - 1992.</p>

A study of cervical cancer screening algorithms / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the feasibility and accuracy of different cervical cancer screening algorithms suitable for different regions, and promote the prevention and control of cervical cancer in China.</p><p><b>METHODS</b>Using the data of a cross-sectional comparative trial of multiple techniques to detect cervical intraepithelial neoplasia in Xiangyuan County, Shanxi Province, conducted in 1999, to evaluate the feasibility and accuracy of different cervical cancer screening algorithms. All the women were screened by six screening tests, including liquid based cytology (LBC), fluorescence spectroscopy, visual inspection with 5% acetic acid staining (VIA), colposcopy, self-sampled HPV DNA and clinician-sampled HPV DNA test, and each woman had histopathological diagnosis. Different screening algorithms were developed by combining the screening tests in parallel or in serial, and the performance indexes of the algorithms such as sensitivity, specificity, colposcopy referral rate and receiver operating characteristic (ROC) curve for detecting the high grade lesions (>or= CIN 2) were compared.</p><p><b>RESULTS</b>Among the algorithms combined by LBC and HPV DNA testing, for the combination in parallel (either cytology was greater than ASC-US or HPV positives), its sensitivity was 100%, specificity was 68.6%, and colposcopy referral rate was 34.4%; for the algorithm of LBC as primary screening test, with ASC-US women triage by HPV DNA testing, its sensitivity was 93.0%, specificity was 89.9%, and colposcopy referral rate was 13.7%; for the algorithm of HPV DNA testing as the primary screening test, with HPV positive women triage by LBC, its sensitivity was 91.7%, specificity was 93.0%, and colposcopy referral rate was 10.6%. ROC analysis showed that LBC primary testing followed by HPV triage and HPV primary testing followed by LBC triage were much better than the combination in parallel (P = 0.0003, P = 0.0002). Among the algorithms with LBC or HPV DNA testing solely as primary screening test, the sensitivity, specificity and colposcopy referral rate of LBC were 94.2%, 77.3%, 25.7% and 87.2%, 93.5%, 10.0%, respectively, for cutoff by ASC-US or by LSIL; the sensitivity, specificity and colposcopy referral rate of HPV DNA testing were 97.6%, 84.8%, 18.8% and 83.5%, 85.9%, 17.1%, respectively, for clinician-sampled and self-sampled. Clinician-sampled HPV DNA testing was better than LBC cutoff by ASC-US or self-sampled HPV DNA testing (P = 0.005, P = 0.002). Among the algorithms combined by VIA and HPV DNA testing, the sensitivity, specificity and colposcopy referral rate were 70.9%, 74.3% and 27.6% for VIA alone as primary screening test; the sensitivity, specificity and colposcopy referral rate were 65.9%, 95.2% and 7.4% for HPV as primary screening test with HPV positive women triage by VIA. HPV primary testing followed by VIA triage was better than VIA alone (P = 0.004).</p><p><b>CONCLUSION</b>Considering the health-resource settings and women's preference, both HPV primary testing followed by LBC triage and LBC primary testing followed by HPV triage are suitable for developed regions, moderately developed regions may choose either LBC or HPV as the screening approach, VIA is a suitable primary screening test in less developed regions, and HPV primary testing followed by VIA triage will be more effective if low cost HPV test is available in the future.</p>

Association between high-risk human papillomavirus DNA load and different histological grades of cervical neoplasia / 中华预防医学杂志

<p><b>OBJECTIVE</b>To determine the association between viral load of high risk human papillomavirus (HR-HPV) and cervical intraepithelial neoplasia (CIN).</p><p><b>METHODS</b>Cervical exfoliated cells were collected from 18 186 women aged 17 -59 from six urban areas and eight rural areas when they were screened in the cross-sectional population-based studies from 1999 to 2008. HR-HPV was detected by the Hybrid Capture 2 (hc2) system, and viral load was measured by the ratio of relative light units to standard positive control (RLU/PC). RLU/PC was categorized for analysis into four groups: negative [0, 1.00), low viral load [1.0, 10.00), moderate viral load [10.00, 100.00), and high viral load > or = 100.00. Cervical lesions were diagnosed by biopsies as normal, CIN 1, CIN 2, CIN 3 and squamous cervical cancer (SCC). Association between HR-HPV viral load and CIN was evaluated by unconditional multinomial logistic regression.</p><p><b>RESULTS</b>The HR-HPV infection rate of the population was 14.51% (2515/17334). 100.00% (29/29) of SCC, 97.63% (206/211) of CIN 3, 93.43% (199/213) of CIN 2, 75.04% (421/561) of CIN 1 and 10.17% (1660/16320) of normal women were positive for HR-HPV DNA. The median RLUs for the HR-HPV positive women with SCC, CIN 3, CIN 2, CIN 1 and normal were 320.85, 158.05, 143.70, 125.34 and 9.64, respectively. There were significant differences among the distributions of viral loads in each lesion (chi2 = 6190.40, P < 0.01). The severity of CIN increased with the viral load (chi2 = 5493.35, P <0.01). Compared with the risks of CINs in HR-HPV negative population, the risks of CINs in low, moderate and high viral loads were increased gradually [OR(95% CI) : CIN 1 : 9.01(6.31 - 12.87), 24.96(18.23 - 34.17) and 68.42(51.40 - 91.08); CIN 2 : 26.44(12.07 - 57.95), 98.53(49.54 - 195.98) and 322.88(168.62 - 618.27); CIN 3+ : 72.89(24.02-221.18); 343.58(121.81-969.09) and >999.99(473.38 - >999.99)], and there were obvious dose-response relationships (chi2trend was 3115.05, 2413.95 and 3098.57, respectively. P< 0.01). In each age group of the HR-HPV positive population,the risks of CIN 2 + in the women with moderate or high viral load were higher than the one with low viral load [OR(95% CI): <35 : 4.71(1.23 - 18.09) and 15.06(4.40 - 51.49); 35 -: 4.01 (1.62 -9.90) and 14.09(6.15 -32.28); 40 - : 3.06(1.52 -6.16) and 7.78(4.05 -14.95); > or =45: 3.50(1.36 -9. 01) and 7.57(3.13 - 18. 30)], and there was a positive correlation between the risk of CIN 2+ and the viral load (chi2trend was 51.33, 66.28, 53.64 and 51.00, respectively. P <0.01). The risk of CIN 2 + was highest among the women aged 40 - with high viral load [OR (95% CI) : 2.02 (1.15 - 3.52)].</p><p><b>CONCLUSION</b>There is strong correlation between the HR-HPV viral load and the severity of CIN, and so is the correlation between the HR-HPV viral load and the risk of CIN 2 +. A moderate to high viral load of HR-HPV should be the major risk factor for the cervical cancer and CIN 2 and CIN 3, and there is a higher risk in the women aged 35 or older than the younger ones. Considering both the age and viral load could help the doctors to manage the screening women more effectively.</p>