The evaluation of human papillomavirus DNA testing in primary screening for cervical lesions in a large Japanese population

To examine the utility of human papillomavirus (HPV) DNA testing for the screening of cervical cancer and its precursors, a prospective cohort study was performed in which a total of 8156 women with a median age of 36 years were enrolled. Two smear samples scraped from the uterine cervix were served for Papanicolaou test and HPV DNA testing (Hybrid Capture-II system). HPV-positive samples were further examined for HPV subtype using a DNA microarray chip. Women with cytologic abnormality or those with high-risk HPV DNA were further examined by colposcopy to determine histologic diagnosis. High-risk HPV DNA was detected in 11% of the general population, with higher prevalence of specific types, including 52, 16, 58, 51, 56, and 18. As expected, younger women were likely to have increased frequency of HPV infection. Notably, HPV DNA testing detected all 45 cases of cervical intraepithelial neoplasia (CIN) 3, while cytologic findings were negative in 6 of these cases. It is of particular interest that CIN was commonly associated with multiple HPV types, while invasive cancers had a single type of HPV. In terms of both sensitivity and positive predictive value in detecting the CIN, HPV DNA testing is superior to cytology. However, most importantly, HPV DNA testing in combination with cytology significantly improved the efficacy to CIN screening.     

Prophylactic human papillomavirus vaccines: the beginning of the end of cervical cancer

Persistent infection with one of the oncogenic human papillomavirus (HPV) types is a necessity for the development of cervical cancer. By HPV vaccination, cervical cancer could become a very rare disease. Two types of HPV vaccines can be distinguished: (i) therapeutic vaccines which induce cellular immunity targeted against epithelial cells infected with HPV and (ii) prophylactic vaccines inducing virus-neutralizing antibodies protecting against new but not against established infections. At present, several vaccines have been developed and tested in clinical trials. The vaccines are generally well tolerated and highly immunogenic. The current clinical data indicate that prophylactic vaccines are very effective against new persistent infections and the development of cervical intraepithelial lesions. The protection is type specific. However, the follow-up of the vaccination trials is still short. The effect of HPV vaccines on future cancer incidence will only be known after decades of follow-up. This article will address the status of recently terminated phase II and currently running phase III trials with prophylactic HPV vaccines.     

Genital human papillomavirus screening by gene chip in Chinese women of Guangdong province

BACKGROUND: Human papillomavirus (HPV) infections are associated with cervical cancer. There were only a few reports and detailed data about epidemiological research of HPV infection in general population of China. AIMS: To determine the prevalence of genital HPV infection in Chinese women of Guangdong province. METHODS: A total of 1705 women were screened by gene chip. All HPV-positive women were further examined by ThinPrep liquid-based cytology test (TCT), and the cervical biopsies of those women with positive HPV-DNA and abnormal TCT were collected for pathological diagnosis. RESULTS: The overall HPV prevalence was 9.03% (154 of 1705), and 72.3% (126 of 154) of total positive samples were high-risk types, with higher prevalence of types 52, 58, 16, 18 and CP8304. For women aged 51 years or older, the overall high-risk HPV prevalence was 12.2% (24 of 179), which was obviously higher than those of other age groups (P < 0.05). CONCLUSIONS: Our results showed that the HPV prevalence in Guangdong is very similar to the world level. Unlike most previous studies, our findings suggest that HPV prevalence increased with age, and that the predominant genotypes in this area were HPV 52 and 58.     

Viral testing for genital human papillomavirus infections: recent progress and clinical potentials

Recent technologic advances indicate the potential role and applications of human papillomavirus (HPV) DNA testing in the routine screening for cervical neoplasia, diagnostic triage of females with inconclusive cervical cytologic smears, and quality control of cytologic and pathologic practices.     

Human papillomavirus testing as an optional screening tool in low-resource settings of Latin America: experience from the Latin American Screening study

Hybrid capture II (HC II) test for oncogenic human papillomaviruses (HPV) was carried out in a cohort of 4284 women at their first clinical visit. Overall prevalence of HPV was 17.1%, decreasing with age from 33.9% among women below 20 years to only 11.0% among those older than 41 years. HPV prevalence was significantly higher among current smokers (odds ratio [OR] = 1.31; 95% CI 1.1-1.6), in women with two or more lifetime sexual partners (OR = 1.9; 95% CI 1.6-2.4), and those women with two or more sexual partners during the past 12 months prior to examination (OR = 1.6; 95% CI 1.2-2.2). HPV detection increased in parallel with increasing cytologic abnormality, being highest in women with high-grade squamous intraepithelial lesion (P= 0.001). Specificity of the HPV test in detecting histologically confirmed cervical disease was 85% (95% CI 83.9-86.1). Sensitivity of the HPV test in detecting histologic abnormalities increased in parallel with disease severity, ranging from 51.5% for cervical intraepithelial neoplasia (CIN) 1 to 96.5% for CIN 3 and 100.0% for cancer, with respective decline of positive predictive value. These data suggest that HPV testing with HC II assay might be a viable screening tool among this population with relatively high prevalence of cervical disease.     

Correlation of human papillomavirus and adeno-associated virus 2 infection in cytology with Korean women

The purpose of our prospective study was to investigate the prevalence of adeno-associated virus (AAV) and human papillomavirus (HPV) 16 and/or HPV 18 infection in Korean women with normal cervical smears and those with HPV-associated cervical intraepithelial neoplasia (CIN) and cancer in cytobrush samples, and to evaluate the correlation between AAV 2 and HPV 16 and/or HPV 18 infection. AAV 2 was detected in CIN I (9.7%), CIN II (20%), CIN III (22.8%), and cancer (10%). HPV 16 was detected in CIN I (42%), CIN II (55%), CIN III (54.3%), and cancer (70%). HPV 18 was detected in CIN I (51.6%), CIN II (50%), CIN III (62.8%), and cancer (43.3%). HPV 16 or HPV 18 was detected in CIN I (18.3%), CIN II (80%), CIN III (71.4%), and cancer (80%). In normal and HPV-infected group, AAV 2 DNA was detected in 16.3% and 4.4% of samples, respectively. HPV 16 was detected in 10.2% of normal patients and in 44.4% of HPV-infected patients, and HPV 18 was detected in 12.2% of normal patients and in 40% of HPV-infected patients. HPV 16 or HPV 18 was detected in 18.3% of normal patients and in 57.7% of HPV infection. The correlation between AAV 2 and HPV 16 was statistically significant in normal and CIN I/II group only, and AAV 2 and HPV 16 and/or HPV 18 showed no correlation. Therefore, the correlation between AAV and HPV were not statistically significant. These data support the previous reports that AAV might not be associated with cervical tumorigenesis.     

The use of vaccines in treating cervical cancer: present status and future prospects

Abstract. Onon TS, Kitchener HC. The use of vaccines in treating cervical cancer: Present status and future prospects.
HPV types are carcinogenic agents in cervical cancer. This view is supported by epidemiological and biological evidence. The oncogenic products and capsid proteins of high risk HPV types are potential targets against which effective immunity may be generated by vaccination. Both therapeutic and prophlylactic immunisation are potential strategies to deal with the widespread problem of HPV infection and possibly established cervical neoplasia. Clinical trials are now underway to evaluate candidate vaccines.     

The prevalence and significance of high-risk human papillomavirus DNA test in southern Malaysia and Singapore

Aim of Study: To investigate the prevalence of high-risk human papillomavirus (HPV) and its associated cytological abnormalities among women attending cervical screening clinics in southern Malaysia and Singapore.
Method: Laboratory results of Hybrid Capture-II (Digene) HPV DNA and liquid-based cytology tests of consecutive women who had screening performed between January 2004 and December 2006 were studied retrospectively.
Results: Of 2364 women studied, the overall prevalence of high-risk HPV DNA detection rate was 25.6%. The prevalence peaked at 49.1% for women between 20 and 24 years old and declined to 23% among women between the age of 30 and 49 years. A small second peak of prevalence rate of 30% was observed among women above the age of 50 years old. 76.1% of the high-risk HPV infection regressed within the study period. An incidence infection rate of 16% was noted among a small group of women who had a second HPV DNA test. A total of 1153 women had both the HPV DNA and the cytology tests. Cytological abnormality (ASCUS or more) was detected in 8.9% in HPV DNA-positive group and in 3.1% in HPV DNA-negative group ( P  < 0.001). The risk ratio for HSIL was 9.8 for HPV-positive women compared to HPV-negative women. The prevalence of cytological abnormalities increased with increasing age of the women.
Conclusion: The epidemiology and clinical impact of high-risk HPV infection for women in Southern Malaysia and Singapore were indistinguishable from experience elsewhere. The apparent moderately high incidence of cervical cancer was explainable by suboptimal screening program.     

宫颈癌医院机会筛查与社区筛查相关因素分析

目的分析宫颈癌医院机会筛查和社区筛查的相关因素。方法对2008年1月至2008年12月在北京市垂杨柳医院妇科门诊行宫颈癌机会筛查和社区筛查妇女的相关因素进行分析,其中门诊机会筛查7223例（机会筛查组）,社区筛查11539例（社区筛查组）。结果社区筛查组年龄[（45.75±9.29）岁]大于门诊机会筛查组[（33.55±10.49）岁],其中社区筛查组年龄〉50岁者占39.8%,初中及以下文化程度者占96.2%,两组筛查妇女年龄比较,差异有统计学意义（P〈0.001）。两组宫颈鳞状上皮内低度病变所占比例（机会筛查组1.2%;社区筛查组0.4%）比较,差异有统计学意义（P〈0.001）;机会筛查组鳞状上皮内高度病变及宫颈癌发生率高于社区筛查组,但差异无统计学意义（P〉0.05）。机会筛查组不同级别的宫颈上皮内瘤变（CIN）和宫颈癌的检出率均高于社区筛查组,差异有统计学意义（P〈0.05）。结论社区筛查人群年龄较大,文化程度低,应重视这一群体防癌知识宣教,提高筛查率。宫颈癌医院机会筛查与社区筛查同样重要。     

Clinical validation of high risk HPV DNA testing versus ThinPrep cytology for primary cervical cancer screening

Objective(s)To compare the validity of the high risk HPV DNA testing using the hybrid capture II technique (HC-II) to ThinPrep cytology for primary cervical cancer screening.DesignCross sectional pilot study.SettingDepartment of Obstetrics and Gynecology, Taiba Hospital, Sabah Al Salem, Kuwait.MethodsConsecutive 1923 cervical smear samples were taken for ThinPrep cytological screening and hr-HPV DNA testing using HC-II assay. Histological diagnoses were obtained from a total of 426 women who had positive results on screening and a group of women with negative screening and suspicious cervix underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment.Main outcome measuresSensitivity, specificity, positive predictive value and negative predictive value of screening methods.ResultsHPV was found positive in 15.5% of cases. 19/22 cases (86.4.1%) with a biopsy diagnosis of CIN2+ had a HC-II positive test. For CIN3, HC-II was positive in all cases (100%). Assuming a similar specificity level, the relative sensitivity of the HC-II test was higher when histologically confirmed high grade lesions (CIN2+ or CIN3+) were observed. HC-II test had the best sensitivity when defining cases as CIN2+ or CIN3+ (98.7% and 100%, respectively). When using the ASCUS+ cytological cutoff, the differences in CIN2+ and CIN3+ sensitivity between HC-II test and ThinPrep cytology were statistically not significant. Specificity of the ThinPrep cytology for any low and high grade histological lesions was clearly >95% when cytological diagnosis LSIL+ cutoff was used and nearly 100% when HSIL+ cutoff was used. All these specificity estimates were high compared with HC-II test. The specificity of the ThinPrep cytology decreased with about 10% when ASCUS+ was the cutoff. At cutoff ASCUS+, specificity of HC-II was comparable or only slightly lower than with ThinPrep ASCUS+ cytology with no statistically significant differences.ConclusionsThinPrep smears and hr-HPV DNA detection by HC-II performed very well with regard to identifying high grade lesions. HPV DNA testing is a promising new technology for cervical cancer prevention and can be used for primary screening in conjunction with cervical cytology for women aged 30 years and older.     

Racial/ethnic differences in HPV 16/18 genotypes and integration status among women with a history of cytological abnormalities

Objective

HPV genotype distribution varies by race/ethnicity, but is unclear whether there are racial/ethnic variations in HPV 16/18 integration in the host genome. We describe HPV16/18 infection and integration status in a racially/ethnically diverse sample of women with a recent abnormal Pap test.

Baseline human papillomavirus status of women with abnormal smears in cervical screening: a 5-year follow-up study in The Netherlands

Objective  To determine in a screening population the human papillomavirus (HPV) status in those with cytological abnormalities and to evaluate the presence of high-risk (HR) HPV with a minimum of 5-year follow up.
Design  Retrospective examination of HPV status on prospectively collected and cytologically screened cervical smears.
Setting  Canisius-Wilhelmina Hospital in Nijmegen, the Netherlands.
Population  Three hundred and fifty-seven women aged 30–60 years, from the population screened.
Methods  Three hundred and fifty-seven women with borderline or higher cytological abnormalities were retrospectively examined for HPV with DNA microarray typing. Follow up was through the nationwide Dutch Pathology database (PALGA).
Main outcome measures  For the cytological abnormalities, the CISOE-A classification was used. HPV was scored as negative or positive. In case of positive HPV polymerase chain reaction, the HPV genotype was determined. The occurrence of cervical intraepithelial neoplasia lesions of grade 3 or higher was considered as endpoint for follow up.
Results  The majority of the women with borderline cytology in this study were HPV negative (87%). Among the HPV-positive women in borderline cytology group, 74% had HR-HPV or probable high-risk types. The overall percentage of HR-HPV types increased with progressive cytological abnormalities. The cytological classifications of borderline dyskaryosis and moderate dyskaryosis contain all types of HPVs, e.g. low risk, HR and unknown risk. The samples with severe dyskaryosis or higher contain only HR types. The negative predictive value for HR-HPV typing in the group with borderline cytological abnormalities is more than 99%.
Conclusions  In cervical screening with an interval of 5 years, HPV can be reliably used as triage point in cases of borderline cytological abnormalities.     

内蒙古镶黄旗地区妇女宫颈病变筛查现状

目的探讨宫颈细胞学(包括巴式涂片及超柏氏薄层液基细胞学)及阴道镜检查筛查内蒙古镶黄旗地区妇女宫颈病变的现状及临床意义。方法2004年7月至2009年1月对内蒙古镶黄旗地区的642例28～67岁有性生活妇女进行宫颈病变筛查,其中557例妇女行传统宫颈巴式涂片法,85例妇女行宫颈超柏氏薄层液基细胞学,并对宫颈细胞学异常者(≥ASCUS)行阴道镜检查及活检。结果642例妇女中宫颈细胞学阳性(≥ASCUS)者34例,占5.3%(34/642),其中ASCUS者22例,占64.7%(22/34);低度鳞状上皮内病变(LSIL)者6例,占17.6%(6/34);高度鳞状上皮内病变(HSIL)者6例,占17.6%(6/34),其中有1例肯定为宫颈癌。宫颈细胞学阴性608例,占94.7%(608/642)。宫颈细胞学阳性34例人群中,行阴道镜活检病理检查者有25例,其中慢性宫颈炎13例(52.0%);CIN1为5例(20.0%);CIN2为4例(16.0%);CIN3为1例(4.0%);浸润癌为2例(8.0%)。结论应重视并及时进行经济不发达地区妇女人群宫颈病变的早期筛查,传统宫颈巴式涂片法及阴道镜活检及病理学检查为可行的筛查方法,有条件者可进行宫颈薄层液基细胞学结合阴道镜活检及病理学检查,对提高早期宫颈癌筛查的准确性效果明显。对内蒙古等西部地区,应在完善技术力量支持、筛查质量控制、建立筛查后的转诊制度及治疗的绿色通道等方面,以降低宫颈癌的发病率。