The prevalence of VAIN,CIN, and related HPV genotypes in Japanese women with abnormal cytology

Vaginal intraepithelial neoplasia (VAIN) is often found by chance. We investigated the prevalence of VAIN and related human papillomavirus (HPV) types in comparison with cervical intraepithelial neoplasia (CIN). This study enrolled 648 women who were referred to the outpatient clinic of Kanazawa Medical University Hospital for abnormal cytology from January 2009 to January 2019. HPV genotypes were determined using Genosearch-31 + 4, which can detect 35 different HPV types. Colposcopy was performed at the first visit by an experienced gynecological oncologist. Among 611 subjects with squamous cell lesions, 107 (17.5%) VAIN cases were identified, and 67 (11.0%) women had both VAIN and CIN. Ultimately, 72 VAIN1, 15 VAIN2/3, 203 CIN1, 249 CIN2/3, 32 cervical squamous cell carcinomas (SCC), and one vaginal SCC (Vag-SCC) were identified. The prevalences of VAIN1, VAIN2/3, and Vag-SCC were 35.5%, 6.0%, and 3.1% of equivalent cervical lesions, respectively. The VAIN patients were older than the CIN patients (P = .002). About half of the VAIN cases were diagnosed during the follow-up. Multiple HPV infections were found in 42.9% of the VAIN and CIN patients. HPV52, 16, 51, 53, and 56 were the most common types in VAIN, whereas HPV16, 52, 58, 51, and 31 predominated in CIN. HPV18 was rare in VAIN, HPV58 was more common in CIN than in VAIN, and HPV53 and HPV73 were more common in VAIN. In conclusion, VAIN1 was identified more frequently than we expected. Various HPV types were identified in the vagina, which is likely a reservoir for HPV.     

Performance of the Abbott RealTime high‐risk HPV test in women with abnormal cervical cytology smears

HPV DNA testing is known to be much more sensitive than cytology, but less specific. A range of HPV and related tests in 858 women referred for colposcopy because of an abnormal smear were evaluated to compare the performances of these tests. This article compared the Abbott test to other tests which had been previously evaluated. This test was a real true test for 14 high‐risk HPV types. The Abbott test was found to be highly sensitive for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) (98.9%) with a specificity of 31.5%. These numbers were comparable with the Qiagen HC2 test, the Roche Linear Array and Amplicor tests, and the Gen‐Probe APTIMA test. Differences between these tests appeared to be related mostly to the choice of cutoff level. An added feature of the Abbott test was the provision of type specific results for HPV 16 and 18. J. Med. Virol. 82: 1186–1191, 2010. © 2010 Wiley‐Liss, Inc.     

Distribution of human papillomavirus among women with abnormal cervical cytology in Kuwait

This study investigates the distribution of human papillomavirus (HPV) in women with abnormal cervical cytology in Kuwait. Two hundred and ninety‐eight (298) abnormal ThinPreps were taken from women seeking routine gynecological care and screened for HPV DNA by real‐time PCR. HPV genotyping was determined by PCR‐based sequencing. HPV DNA was detected in 152 women (51%), and 29 different HPV genotypes were detected, comprising 16 high‐risk (HR) (16, 18, 31, 33, 35, 39, 45, 51, 53, 56, 58, 59, 66, 68, 73, 97), nine low‐risk (LR) (6, 11, 54, 61, 74, 81, 90, 102, 106), and four intermediate‐risk (IR) (62, 67, 84, 87). HPV16 had the highest prevalence (24.3%), followed by HPV11 (13.8%), HPV66 (11.2%), HPV33 (9.9%), HPV53 (9.2%), HPV81 (9.2%), HPV56 (7.9%) and HPV18 (6.6%). HPV prevalence was 86, 67, and 89% in women with invasive cervical carcinoma (ICC), high‐grade squamous intraepithelial lesion (HSIL) and low‐grade squamous intraepithelial lesion (LSIL), respectively. As for age distribution, 69% of all HPVs were found in women aged 20–29 years, and the HPV incidence rate deceased with increasing age. The proportion of single infections decreased as the severity of the cytological diagnosis increased, while the proportion of multiple infections increased. This study is the first of its type in Kuwait and one of few in the Middle East. The findings are consistent with the hypothesis that HPV infection is the primary cause of cervical neoplasia. They support HPV vaccine research to prevent cervical cancer and efforts to develop HPV DNA diagnostic tests. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Concomitant infections with human papillomavirus and various mycoplasma and ureaplasma species in women with abnormal cervical cytology

PurposeThe objective of the present study is to verify possible association between infections with mycoplasmas and ureaplasmas and the presence of HPV infections in women diagnosed with abnormal cervical cytology.Material/MethodsThe investigation included 387 non-pregnant women among whom: 62 were diagnosed with ASCUS, 167 with LSIL, 27 with HSIL, 49 with cervical carcinomas, and 82 females with normal cytology.The presence of HPV infection and identification of both ureaplasma and mycoplasma were confirmed by PCR using specific primers.ResultsHPV infections were demonstrated in 156 females (40%), with mycoplasmas and/or ureaplasmas were confirmed in 93 cases (24%).In HPV-positive patients, infections with mycoplasmas/ureaplasmas were more frequent, particularly for ureaplasmas (U. urealyticum p=0.004, U. parvum p=0.027). The percentage of females infected with U. urealyticum significantly increased in women diagnosed with cervical carcinoma as compared to controls.The statistical analysis demonstrated that the risk of HPV infection while already infected with any of the four analyzed species of Mycoplasmataceae increased two-fold. With concomitant of U. urealyticum infection, the risk of HPV infection was 4.7-fold greater than in the absence U. urealyticum infection.ConclusionSince the presence of U.urealyticum associates significantly with the HPV infection, genotyping of the ureaplasma species should be recomended.     

CASP8 promoter polymorphism is associated with high-risk HPV types and abnormal cytology but not with cervical cancer

Only a small fraction of women infected with human papillomavirus (HPV) progress to cervical cancer pointing to additional risk factors including host genetics that might play a role in development of cervical cancer. Caspase-8 (encoded by CASP8 gene) is crucial in generating cell death signals to eliminate potentially malignant cells. Genetic variation in CASP8 might influence the susceptibility to cancer. CASP8 -652 6N ins/del polymorphism has been previously reported to influence the progression to several cancers including cervical cancer. This polymorphism was investigated in 445 women of black African and Mixed Ancestry origin with invasive cervical cancer and 1,221 controls matched (1:3) by age, ethnicity, and domicile status. Genotyping for CASP8 -652 6N ins/del was done by PCR-RFLP. In the control women cervical disease was detected by cervical cytology. The CASP8 -652 6N del/del genotype did not show any significant association (P=0.948) with cervical cancer. Further analysis within the controls showed a weak association (P=0.048) of this polymorphism with abnormal cytology in both ethnicities and high-risk HPV infection (P=0.030) only in the black Africans. This is the first study of the role of CASP8 -652 6N ins/del polymorphism in cervical cancer in an African population. These results show that CASP8 -652 6N del/del genotype increases the risk of abnormal cytology and high-risk HPV infection but does not show an association with cervical cancer. This result points towards an important role of CASP8 in HPV infection and in the development of pre-cancers.     

Molecular detection of Chlamydia trachomatis and HPV infections in cervical samples with normal and abnormal cytopathological findings

It has been suggested that Chlamydia trachomatis (CT) and human papillomaviruses (HPV) co-infection could contribute to development of intraepithelial lesions. In this study, HPV and CT-DNA were investigated in 250 cervicovaginal samples of patients from Minas Gerais, Brazil. The cytological analysis revealed that 70% of samples (175) were negative, 5.2% (13) presented atypical squamous or glandular cells of undetermined significance (ASCUS/AGUS), 12.4% (31) presented low-grade squamous intraepithelial lesion (LSIL), 10.8% (27) high-grade squamous intraepithelial lesion (HSIL), and 1.6% (4) invasive carcinoma. HPV-DNA and HPV/CT co-infection was observed in 40% (100/250) and in 5.2% (13/250) of samples, respectively. Among the positive cytological samples, HPV-DNA was detected in 73.3% and CT-DNA in 9.33% and in 13%, if only the HPV positive samples were considered. The highest co-infection rate (15.4%) was observed among ASCUS/AGUS samples. Although a significant association was found for HPV infection and the precursor lesions of cervical cancer, it was not possible to establish a significant association between these lesions and CT or HPV/CT co-infection.     

人乳头瘤病毒检测在宫颈病变中的应用价值

Objective To detect the human papillomavirus(HPV) infectious condition in women with abnormal cytology and evaluate its values in the screening of high grade cervical intraepithelial lesion.Method 1O1 patients who underwent thinprep cell test(TCT) with abnormal cervical cytology were selected to undergo HPV test, all subjects also received tissue biopsy at the same time. Results ( 1 )Among the 101 patients,the incidence rates of high risk HPV infection of those with ASCUS, LSIL, HSIL and squamous cell carcinoma were 84. 2% ,88.6% , 100. 0% and 2/2 respectively. (2)Among the patients with abnormal cytology,the number of patients with pathologically confirmed results of CIN Ⅰ and CIN Ⅱ or worse were 20 and 81, the incidence rates of high risk HPV infection of those with CIN Ⅰ and CIN Ⅱ or worse were 60.0% and 97.5% respectively. (3) In the ASCUS group, the incidence rates of CIN Ⅱ or worse with high risk HPV infection were 87.5% and the incidence rates of CIN Ⅱ or worse without high risk HPV infection were 16.7%. (4)The prevalence of high risk HPV types from highest to lowest order were follow: HPV16 (39. 6% ) ,58( 17. 8% ) ,52 ( 16. 8% ), 18 ( 9. 9% ) ,33 ( 9.9% ). Conclusions The infection rate of high risk HPV was positively correlated with the levels of cervical lesions. HPV test is a good triage approach for the patients with ASCUS. HPV16,58,52,18,33 are the most common in the patients of cervical lesions.     

人乳头瘤病毒检测在宫颈病变中的应用价值

Objective To detect the human papillomavirus(HPV) infectious condition in women with abnormal cytology and evaluate its values in the screening of high grade cervical intraepithelial lesion.Method 1O1 patients who underwent thinprep cell test(TCT) with abnormal cervical cytology were selected to undergo HPV test, all subjects also received tissue biopsy at the same time. Results ( 1 )Among the 101 patients,the incidence rates of high risk HPV infection of those with ASCUS, LSIL, HSIL and squamous cell carcinoma were 84. 2% ,88.6% , 100. 0% and 2/2 respectively. (2)Among the patients with abnormal cytology,the number of patients with pathologically confirmed results of CIN Ⅰ and CIN Ⅱ or worse were 20 and 81, the incidence rates of high risk HPV infection of those with CIN Ⅰ and CIN Ⅱ or worse were 60.0% and 97.5% respectively. (3) In the ASCUS group, the incidence rates of CIN Ⅱ or worse with high risk HPV infection were 87.5% and the incidence rates of CIN Ⅱ or worse without high risk HPV infection were 16.7%. (4)The prevalence of high risk HPV types from highest to lowest order were follow: HPV16 (39. 6% ) ,58( 17. 8% ) ,52 ( 16. 8% ), 18 ( 9. 9% ) ,33 ( 9.9% ). Conclusions The infection rate of high risk HPV was positively correlated with the levels of cervical lesions. HPV test is a good triage approach for the patients with ASCUS. HPV16,58,52,18,33 are the most common in the patients of cervical lesions.     

HPV16、58型感染导致宫颈微环境中免疫因子变化及宫颈细胞中病毒整合的初步研究

目的：探讨人乳头状瘤病毒（Hapillomavirus,HPV）16和58型感染导致宫颈局部微环境中免疫因子白介素（Interleukin,IL）-12、IL-4,干扰素（Interferon,IFN）-γ浓度变化及宫颈细胞中HPV16/58病毒DNA整合与宫颈病变进展的关系。方法：收集2012年8月～2013年5月在广西医科大学附属肿瘤医院妇瘤科住院行HPV DNA分型检测,且组织病理结果诊断为宫颈癌患者的宫颈灌洗液共89例及宫颈脱落细胞140例,根据HPV分型结果将89例宫颈灌洗液分组为：①HPV16（＋）58例;②HPV58（＋）31例。应用酶联免疫法（Enzyme linked immunosorbent assay ,ELISA）法检测89例患者宫颈微环境中免疫因子IL-12、IL-4、IFN-γ的浓度;将140例宫颈脱落细胞根据HPV分型结果分组为：①HPV16（＋）106例;②HPV58（＋）34例。采用荧光定量PCR（ qRT-PCR）检测HPV16/58的E2和E6基因,根据E2/E6拷贝数比值判定HPV16/58 DNA的存在状态。结果：①HPV16（＋）组中IL-4浓度明显高于HPV58（＋）组（ P＜0.05）;IL-12、IFN-γ的浓度明显低于HPV58（＋）组（ P＜0.05）。②HPV16 DNA与HPV58 DNA的存在状态有着显著差异（ P＜0.05）,HPV16 DNA整合比率比HPV58 DNA整合比率明显增大。结论：HPV16和58型感染不但可以导致宫颈细胞外局部免疫微环境中的IL-12、IFN-γ的降低和（或） IL-4的升高,还可导致病毒在宫颈细胞内整合,通过宫颈细胞内外变化导致宫颈病变甚至宫颈癌的发生;HPV16较HPV58更容易造成宫颈组织发生癌变。     

Prevalence of anal cytological abnormalities in women with positive cervical cytology

The objective of this study was to estimate the prevalence of cytological abnormalities of the anal mucosa in women with positive cervical cytology, but without macroscopic anal lesion. Ultimately we postulated if the anal mucosa may be a reservoir of HPV, which would allow the reinfection of cervix. Forty‐nine patients with abnormal cervical cytology were selected for this work. In a period not exceeding one week of collecting cervix cytology, two swab specimens of the anal canal were also collected. Women diagnosed with cervical HSIL by Pap smear were referred for colposcopy with biopsy of the lesions, to confirm the cytologic diagnosis and ablation of the lesion. We demonstrated a high prevalence of anal squamous intraepithelial lesions in patients with cervical squamous intraepithelial lesions (29 of the total of 49 patients = 59.2%). Of the 20 cases of cervical LSIL, 11 (55%) had abnormal anal cytology. Of the 26 cases with cervical HSIL, 16 (61.5%) had abnormal anal cytology. So, there was a discrete higher prevalence of abnormal anal cytology in cases of high‐grade cervical squamous lesions (cervical HSIL). These results help to support the hypothesis that the anal mucosa is a reservoir of HPV, which can be a source of re‐infection for the cervix. However, there was no significant association between the practice of anal sex and the prevalence of anal cytological abnormalities. These facts are epidemiologically important for future programs for population eradication of cervical lesions related to HPV. Diagn. Cytopathol. 2011;39:323–327. © 2010 Wiley‐Liss, Inc.     

人乳头瘤病毒检测在宫颈病变中的应用价值

目的了解宫颈细胞学异常患者中人乳头瘤“毒（HPV）的感染状况,评估HPV检测在宫颈病变筛查中的价值。方法随机选取宫颈薄层液基细胞学检测异常的101例患者进行了HPV检测,同时行组织病理学检查。结果（1）101例宫颈细胞学异常患者中,细胞学为ASCUS、LSIL、HSIL、鳞状细胞癌时高危型HPV阳性率分别为84．2％、88．6％、100．0％和2／2;（2）10l例细胞学异常患者中20例为CINI,81例为CINⅡ及以上级别,高危型HPV阳性率存CINI、CINⅡ及以上级别分别为60％、97．5％;（3）ASCUS组中,高危型HPV阳性患者中CINⅡ及以上病变的发生率为87．5％,HPV阴性患者中CINⅡ及以上病变的发生率为16．7％;（4）高危型HPV型别分布由高到低分别为HPVl6型39．6％（40／101）,HPV58型17．8％（18／101）,HPV52型16．8％（17／101）,HPVl8型9．9％（10／101）以及HPV33型9．9％（10／101）。结论高危型HPV感染率与宫颈病变级别呈正相关;HPV检测可作为ASCUS患者的有效分流手段。宫颈病变患者中高危型HPV感染以16、58、52、18、33型为主。     

The prevalence of abnormal cervical cytology in women with infertility

The aim of this study was to compare the frequency of abnormal cervical cytology in women with infertility problems with that of fertile women by using ThinPrep® liquid‐based Pap Tests™. A retrospective case–control study for over 2 years was conducted. The cases included all women with infertility problems who had Pap tests during their infertility treatment period. The cases were further subdivided into primary and secondary infertility groups. The control group included all women without infertility problems who had routine Pap tests in the same period. The age and demographic features were adjusted and matched for both groups. Statistical analysis included chi‐square test and Fischer exact test. The infertility group (n = 490) showed significantly (P < 0.05) more abnormal cervical squamous epithelial abnormalities (48 positive cases, 9.8%) than the controls (n = 7,150, 216 positive cases, 3%). Women with secondary infertility had more epithelial abnormalities and more high‐grade lesions than women with primary infertility. Women with infertility had statistically significant higher frequency of squamous intraepithelial lesions than women without infertility problems of similar age and demographic background. The data suggest that women with infertility might benefit from more frequent cervical cytology screening. Diagn. Cytopathol. 2010;38:791–794. © 2009 Wiley‐Liss, Inc.     

The prevalence of abnormal cervical cytology in women with systemic lupus erythematosus

To compare the frequency of abnormal cervical cytology in women with systemic lupus erythematosus (SLE) with that of healthy women without connective tissue diseases by using ThinPrep® liquid based Pap Tests^TM. A retrospective case‐control study over 2 years was conducted. The cases included all women with SLE who had Pap tests during their treatment period. The control group included all women without SLE or other connective tissue diseases (CTDs) that had routine Pap tests in the same period. The age and demographic features were adjusted and matched for both groups. Statistical analysis included Chi‐Square test and Fischer exact test. The SLE group (n= 55) showed significantly (P < 0.05) more abnormal cervical squamous epithelial abnormalities [14 positive cases (25.4%) than the controls (n = 8,175, with 285 positive cases (3.5%)]. Women with SLE had statistically significant higher frequency and prevalence of squamous intraepithelial lesions than women without SLE of similar age and demographic background. The data suggested that women with SLE might benefit from more frequent cervical cytology screening. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.     

HPV prevalence among healthy Italian male sexual partners of women with cervical HPV infection

Genital human papillomavirus (HPV) is the causative agent of cervical cancer and is the most common sexually transmitted infection. Only limited and controversial data are available regarding HPV transmission in male sexual partners of women with cervical intraepithelial neoplasia (CIN). The aim of this study was to investigate the prevalence and the genotype distribution of HPV in penile scrapings of a series of Italian men, who had no visible penile lesions and were partners of women who were affected, or had been affected previously by cervical intraepithelial neoplasia or who were infected with HPV. The concordance of the viral group in the infected partners was determined. A total of 77 penile scrapings were screened for HPV infection by the polymerase chain reaction, while 59 cervicovaginal brushings of their female partners were tested. 35% of evaluable male samples and 64% of female sexual partners were found to be HPV positive. In the 55 simultaneously evaluable couples, a concordance of 45% was found, 11 couples (20%) with both partners being HPV negative and 14 couples (25%) with both partners HPV positive (P=0.001). Six out of the 14 couples (43%), where both partners were HPV positive, harbored the same HPV genotype group. These data, although preliminary, could support further the hypothesis that male HPV infection is more frequent in sexual partners of HPV positive or women with cervical intraepithelial neoplasia indicating that men could represent an important source of HPV transmission between sex partners.     

High prevalence of human papillomavirus type 58 in patients with cervical pre‐malignant lesions in southern Brazil

Cervical cancer is the second most common type of cancer in women worldwide. Several human papillomavirus (HPV) genotypes, sexual behavior, and socioeconomic profile represent major risk factors for the development of this carcinoma. Cervical invasive cancer is preceded by cellular abnormalities that can be identified by cytological or histological exams. In order to determine the prevalence and genotypes of HPV in women with abnormal cytology or histopathology, cervical cell samples from 256 patients were evaluated for the presence of HPV/DNA by polymerase chain reaction (PCR), followed by virus genotyping by restriction fragment length polymorphism (RFLP). A total of 113 samples (51.2%) were HPV/DNA positive. Viral genotyping showed that the most prevalent genotypes were HPV 16 (34.7%) and 58 (13.8%), followed by HPV 33 (9.72%), 11 (8.33%), 18 (5.55%), 53 (5.55%), and 6 (4.2%). Four samples (5.55%) exhibited multiple infections due to the great similarity of socioeconomic characteristics and sexual behavior of HPV positive women, it was not possible to establish a risk profile for female HPV infection. J. Med. Virol. 81:1270–1275, 2009. © 2009 Wiley‐Liss, Inc.     

预防性重组HPV58-减毒志贺氏杆菌载体活疫苗的研制及免疫学特性

目的：构建预防性重组HPV58-减毒志贺氏杆菌载体活疫苗，并研究其免疫学特性。方法：克隆HPV58L1基因并重组入自杀载体pCVD442，减毒志贺氏杆菌Sf301：△virG、辅助质粒PRK2013、重组自杀载体pCVD442-HPV58L1进行筛选杂交，经氨苄抗性培养基、刚果红培养基双重选择，获得重组的含HPV58L1基因的减毒志贺氏杆菌菌株。Western blot检测HPV58L1蛋白表达。用豚鼠角结膜炎模型进行疫苗动物免疫试验，ELISA检测豚鼠血清中特异性抗体，ELISPOT检测豚鼠脾及淋巴结中抗原特异性IgG、Iga产生细胞频数。结果：Western blot法证实该菌株可表达HPV58L1蛋白。豚鼠免疫保护试验发现：HPV58L1-减毒志贺氏杆菌不引起角结膜炎，经用野生型sf301攻击后有80％豚鼠不发病。免疫后第20天，免疫豚鼠血中抗HPV58L1特异性IgG、IgA明显升高，而对志贺氏杆菌菌体抗原（LPS）仅产生低效价的IgG抗体。ELISPOT结果显示，脾和淋巴结的IgA-ASC及IgG-ASC明显升高。结论：成功构建了预防性重组HPV58-减毒志贺氏杆菌载体活疫苗，能诱发免疫动物较强的体液免疫反应，激发保护性抗体的产生。