HPV detection and genotyping as an earlier approach in cervical cancer screening of the female genital tract

Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia (CIN) and cervical cancer. More than 100 virus genotypes have been identified so far, some of them strongly associated with the development of neoplasia. The aim of this study was to evaluate the prevalence of the different HPV genotypes in women presenting no cytological alterations in cervical cells, in women presenting light alterations, and in women presenting severe alterations at routine gynecological examination. We retrospectively analyzed 97 HPV results of women submitted to cervical cancer screening compared to their Papanicolaou and colposcopy examinations. Data were analyzed individually and within groups to correlate the HPV genotypes identified by polymerase chain reaction (PCR) and the respective alterations in cervical cells. Among the nine cases diagnosed as CIN I (9.3%), two were positive for low-risk HPV genotypes (22%), and the other seven were negative for HPV by PCR (78%). CIN II or CIN III diagnoses were associated with positive HPV results by PCR in four cases (36%), for high-risk as well as low-risk genotypes. There were two patients with severe cytological alterations in cervical cells, but with an indeterminate HPV genotype (18%), and one case with a negative HPV result (9%). Among the 57 cases without cytological alterations, seven were positive for low-risk HPV (12%) and two for high-risk HPV genotypes (3.5%). In the 48 remaining cases, we observed one with an indeterminate HPV genotype (2%), and the other 47 were negative for HPV by PCR (47%). Our study demonstrates an important prevalence of high- and low-risk HPV genotypes in our population, including those not present in the commercially available vaccine, even in patients with no evidence of cytological alterations in cervical cells. These results highlight the usefulness of HPV detection and typing as an early approach for cervical cancer screening and prevention.     

人乳头状瘤病毒与妇科其他常见病原微生物感染关系的调查

目的 探讨人乳头状瘤病毒(HPV)感染与妇科其他常见病原微生物感染的关系.方法 收集2007年6月至2008年12月在浙江省温岭市第一人民医院妇科门诊就医的857例妇女的宫颈和阴道拭子标本,采用PCR技术检查HPV DNA及其基因分型,采用链替代扩增方法检测沙眼衣原体,其他妇科病原微生物的检测按照常规方法进行,统计分析结果资料.结果 本研究收集的857例妇女中检测出HPV阳性266例,阳性率为31.0%(266/857).在266例HPV阳性妇女中,除4例为混合基因型,其余262例共检测出35种HPV的不同亚型,各亚型按所出现频率>5%排列,分另是HPVl6(14.5%,38/262)、HPV58(9.2%,24/262)、HPV53(8.0%,21/262)、HPV42(6.1%,16/262);HPV高危型和可能高危型占58.8%(154/262),HPV低危型占27.9%(73/262),HPV未知危险型占13.4%(35/262).宫颈脱落细胞检测结果显示,63.2%(168/266)的HPV阳性妇女未见异常细胞,3.8%(10/266)是高度鳞状上皮内病变(HSIL),29.7%(79/266)是低度鳞状上皮内病变(LSIL),3.0%(8/266)是未明确诊断意义的不典型鳞状上皮细胞(ASCUS).在所有研究对象中未检测出淋病奈瑟菌,人型支原体在所有研究对象中仅检测出2例.logistic回归分析显示,HPV感染与沙眼衣原体和解脲支原体[>10000颜色变化单位(CCU)/ml]感染具有显著相关性(P均<0.01),而细菌性阴道病、无乳链球菌、假丝酵母菌、阴道毛滴虫和解脲支原体(≤l0000 CCU/ml)与HPV感染无相关性(P均>0.05);但患细菌性阴道病妇女的HPV阳性率为42.6%.沙眼衣原体是HPV感染的高危因素(OR=2.82,95%CI为1.74～4.57).结论 细菌性阴道病与HPV感染虽不具有相关性,但其在HPV阳性妇女中普遍存在.HPV感染与沙眼衣原体和解脲支原体感染具有相关性;沙眼衣原体感染会增加HPV感染的机会.     

Prevalence of high risk human papillomavirus types 16/18 in cytologically abnormal cervical smears in Alexandria,Egypt. A cytological and molecular study

IntroductionIn Egypt, cervical cancer ranks as the second most frequent cancer after breast cancer, among women between 15 and 44 years of age. High-risk human papillomavirus (HPV) 16 and 18 detection holds the potential to be used as a tool to detect women, at risk for consequent development of cervical cancer because of their predominance and potentially greater oncogenic nature than other high risk HPV subtypes.ObjectiveTo determine the prevalence of high-risk HPV 16/18 DNA in women with abnormal cervical cytology.Subjects and methods45 cases were collected from Egyptian women seeking routine gynecologic care. Ten cytologically normal cervical smear cell samples were included in the study as a control to be tested for the presence of HPV 16/18 DNA and were collected from asymptomatic patients having cystorectocele or coming for loop insertion or removal. The 45 specimens were subjected to real-time polymerase chain reaction, using multiplex HPV 16 and 18 PCR kit.Results45 cervical smears were collected in the present study. Cytopathological examination revealed that 5 (11.1%) were ASCUS, 8 (17.8) were LSIL, 5 (11.1%) were HSIL, 1 (2.2%) was squamous cell carcinoma (SCC), 1 (2.2%) was adenocarcinoma and 25 (55.6%) were benign (inflammatory). 20 patients with abnormal cervical cytology and 10 controls were included in the present study. In patients with abnormal cervical cytology, 5 (25%) were ASCUS, 8 (40%) were LSIL, 5 (25%) were HSIL, and 1 (5%) was SCC and 1 (5%) was adenocarcinoma. Statistical analysis revealed a significant difference between patient and control groups as regards regularity of menstruation where irregular menstruation and higher prevalence of menopausal women, abnormal vaginal bleeding, menorrhagia, vaginal infection, and abnormal cervical appearance were encountered in patients. A statistically significant higher prevalence of married women was found in the control group. There was no significant difference in the distribution of patients and control as regards HPV 16 or HPV 18 in which 20% of patients were HPV 16 positive and 10% of patients were HPV 18 positive compared with none in the control group. 6 were positive either for HPV 16 or 18, while 39 were negative. The HPV 16/18 positive patients had significantly higher age and marital duration when compared with HPV 16/18 negative group. Significantly, most of the HPV 16/18 positive patients were menopause. A significantly higher prevalence of women with cervicitis, contraceptive users and married women was in the HPV 16/18 negative group.ConclusionThe study generates epidemiological data of prevalence of HPV 16/18 in cytologically abnormal cervical smears in women seeking routine gynecologic care at the outpatient clinics of the Obstetrics and Gynecology Department at El Shatby University. High-risk HPV DNA testing by PCR of cervical samples diagnosed according to the Bethesda 2001 guidelines may benefit the management of patients with abnormal cervical smears, especially among women aged 46 years and older, in menopausal women and in women complaining of PMB. Therefore, HPV DNA testing should be made use of as an adjunct to cervical smears.     

新疆南部维吾尔族妇女宫颈癌及癌前病变HPV16 E6/E7基因突变序列分析

目的:探讨新疆南部地区维吾尔族妇女HPV16E6/E7基因突变与宫颈病变及宫颈癌发生的关系。方法:提取上述地区40例宫颈癌及80例CINⅠ～Ⅲ组织的HPV16DNA,用PCR扩增其E6/E7基因并对产物测序,然后以德国标准株HPV16DNA为原型进行对比,分析其突变情况。结果:HPV16E6突变中L83V占80.6%(25/31),D25E占16.1%(5/31),E7突变中R77C占33.3%(5/15),N29S占26.7%(4/15)。结论:新疆宫颈病变及其癌变组织中HPV16E6/E7以L83V,D25E,R77C,N29S为主要突变株,欧洲型突变为主,与亚洲型突变同时出现是该地区的主要突变特点。     

The possibility of viral etiology in cervical carcinogenesis

Oncogenic potential of herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) which are both associated with occurrence of cervical cancer and the mechanism of oncogenesis by these viruses were investigated by transformation experiments in vitro. The results were obtained as follows. 1) HSV-2 induced neoplastic transformation of normal diploid cells is a multistep process. Cervical cancer associated antigen AG-4 is encoded within the specific region of HSV-2 DNA which converts immortalized cells to tumorigenic lines. 2) Tumor cells express cellular oncogene at a final stage of neoplastic transformation induced by HSV-2 and "hit and run" theory is applicable to oncogenesis of this virus. 3) Complete carcinogenesis can be mediated by HPV-16 or HPV-18 DNA under collaboration with other cofactors such as HSV-2. 4) It is suggested that neoplastic transformation induced by HPV-18 DNA is based on "hit and run" oncogenesis. 5) HPV-16 or HPV-18 DNA can immortalize primary diploid cells and convert them to fully tumorigenic phenotype by repeating cell passage. 6) It has been experimentally proved that the difference in transforming potential exists between HPV 6/11 and HPV 16/18. 7) Amplification and overexpression of c-myc oncogene was detected in transformed cells obtained by HPV-16 transfection. While overexpression of c-myc was detected in transformed cells induced by HPV-18 DNA, but no amplification was observed. On the other hand, detection of HPV, DNA and amplification or overexpression of protooncogenes was performed in cervical intraepithelial neoplasias (CIN) and invasive cervical carcinomas. The results were summarized as follows. 1) HPV DNA was detected in approximately 70% of a population with CIN by in situ hybridization. CIN II showed the highest incidence of positive HPV DNA (91%), and the positive ratio decreased in CIN III (56%). 2) Immunohistochemical study of paraffin-embedded specimens with monoclonal antibodies to oncogene products revealed that only some of cervical invasive carcinomas expressed c-myc protein, ras p21 or EGFR. 3) HPV DNA was detected in 46% of invasive cervical carcinomas by Southern blot hybridization. The percentage of patients with positive results for HPV 16/18 was 29%. However, it increased up to 58% by use of polymerase chain reaction (PCR), suggesting that there are many cervical cancer tissues in which a number of cells lack viral DNA. 4) Northern blot hybridization analysis revealed overexpression of c-myc mRNA in 30% of cervical invasive carcinomas although amplification of c-myc oncogene was detected in only one of invasive carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chlamydia trachomatis and herpes simplex virus 2 infection in vulvar intraepithelial neoplasia associated with human papillomavirus

BACKGROUND: The role of viral and bacterial co-infection is stressed in VIN. A view that VIN is a sexually transmitted disease made the area of research larger and stimulated scientists to seek other sexually transmitted factors, among which Chlamydia trachomatis and Herpes simplex are frequently examined. PURPOSE: The aim of the study was to evaluate the frequency of occurrence of HPV DNA and the frequency of co-infection with Herpes virus type 2 and Chlamydia trachomatis in VIN. MATERIAL AND METHODS: We identified archival diagnostic phase tissue specimens from 41 cases of vulvar intraepithelial neoplasia III. From the same paraffin blocks containing material from the margins of surgical sections during vulvectomy, normal epithelial tissue fragments were collected. They constituted the control group. Lesion characteristics were examined in comparison with the presence of HPV DNA, HSV-2 and Chlamydia trachomatsis. Identification was performed using PCR. RESULTS: In the study group HPV infection was found in 75.6% of cases. In 73% of cases it was HPV 16. In the control group we found HPV 16 DNA in only one case (2.43%). In the HPV positive study group HPV 16 was found in 30 (30/31) cases. In only one case (1/31) it was HPV 18 type. In the study group of 41 cases with VIN, HSV-2 infection was found in six cases (14.63%). In comparison with the control group (9.75%) the difference was not statistically significant. The frequency of occurrence of Chlamydia trachomatis in the analyzed study material was 14.63% (6/41) and in the control group it was 9.75% (4/41). The difference was not statistically significant. Statistical analyses of correlations between the occurrence of DNA HPV and HSV-2 as well as of HPV and Chlamydia trachomatis showed no correlation in either case. CONCLUSION: No correlation was found between the frequency of occurrence of HPV and HSV-2 and HPV and Chlamydia trachomatis in either group.     

新疆维吾尔族妇女子宫颈癌活检组织中人类乳头状瘤病毒DNA的检测

目的：研究我国宫颈癌高发区新疆维吾尔族妇女宫颈癌与人类乳头状瘤病毒（ＨＰＶ）感染的关系。方法：对６５例新疆维吾尔族妇女的宫颈癌活检组织标本，应用原位杂交法检测ＨＰＶ６／１１、１６／１８和３１／３３／３５ＤＮＡ；Ｌ１共有序列引物聚合酶链反应（ＰＣＲ）及Ｅ６特异型引物ＰＣＲ检测其中的５８例ＨＰＶ６、１６和１８ＤＮＡ。结果：６５例宫颈癌患者中，原位杂交法检测ＨＰＶＤＮＡ有２８例阳性（４３．１％）；Ｌ１ＰＣＲ和Ｅ６ＰＣＲ检测ＨＰＶＤＮＡ阳性分别为１３例（２２．４％）和４５例（７７．６％）。结论：对宫颈癌标本中的ＨＰＶＤＮＡ检测，Ｅ６特异性引物ＰＣＲ敏感性最高，Ｌ１ＰＣＲ及原位杂交相对较低。新疆维吾尔族妇女宫颈癌发病与ＨＰＶ感染有密切关系。     

22234例子宫颈高危型HPV感染及亚型分布研究

目的:分析17种型别的高危型人乳头瘤病毒(HPV)在22234例子宫颈癌筛查中的感染率及亚型分布特点。方法:回顾性分析2018年1月1日至2019年1月1日22234例于华中科技大学同济医学院附属协和医院行子宫颈癌筛查患者高危型HPV感染率及感染亚型。结果:22234例接受子宫颈癌筛查患者中,一种或以上高危型HPV阳性者3574例(16.1%),其中HPV16或(和)HPV18阳性者703例(3.2%)。在3574例高危型HPV阳性女性中,最常见的高危HPV感染是HPV52(24.4%),其次为HPV58(16.5%)、HPV16(14.0%)、HPV53(12.6%)和HPV39(8.6%)。与HPV16阴性患者相比,在HPV16阳性的患者中,除HPV31、HPV35、HPV45、HPV26和HPV82以外的12种高危型HPV的感染风险均显著降低约2~5倍(OR 0.169~0.530,P<0.05);与HPV18阴性患者相比,HPV18阳性的患者中HPV16、HPV33、HPV39、HPV51、HPV52、HPV58和HPV53的感染风险均显著下降(P<0.05)。结论:女性高危型HPV感染率较高,最常见的高危型HPV是HPV52和HPV58感染,并且HPV16、18感染对多个其他型别高危型HPV感染有保护作用。     

The prevalence of HPV16DNA in normal and pathological cervical scrapes using the polymerase chain reaction.

Human papillomavirus (HPV) has been implicated in the development of cervical cancer. Newly developed molecular techniques have facilitated HPV identification and typing of cervical lesions. Several studies have suggested a strong correlation between HPV16 and intraepithelial cervical neoplasia. However, there is no agreement on this point since HPV16 is detected also in normal cervical tissue. We have amplified the L1 region of HPV16 DNA using the polymerase chain reaction (PCR) technique and analyzed the HPV16 prevalence in cytological scrapes of 201 Italian sexually active patients. One hundred twenty-four of these women had normal cytologic and colposcopic examination, while seventy-seven women had normal or abnormal cytology and a cervical lesion detectable by colposcopy. Within this latter group, 25 of 77 women (32.4%) were positive for HPV16 DNA, compared to 11 of 124 samples (8.87%) from women with normal cytology and colposcopy. The present results confirm the high efficiency of the PCR technique in detecting HPV16 DNA from cervical scrapes and suggest that this analysis should become a method of choice in clinical studies.     

Relationship between HPV typing and abnormality of G1 cell cycle regulators in cervical neoplasm

OBJECTIVE: In tumorigenesis, loss of function of the G1 pathway (p16-CDK4/cyclinD1-pRB pathway (RB pathway) and p14-MDM2-p53 pathway (p53 pathway)) is a theoretically essential event. The simultaneous analysis of all components of the RB and p53 pathway may be able to explain cervical tumorigenesis. However, there are no reports in which all components of the G1 pathway and HPV typing were examined simultaneously in cervical cancer. METHODS: We examined HPV typing and the status of the G1 pathways simultaneously by PCR-SSCP, multiplex PCR, methylation-specific PCR, and immunohistochemical techniques in cervical neoplasia. A total of 105 samples (normal, 10; cervical intraepithelial neoplasm (CIN), 42; invasive cancer (IC), 53) were included. RESULTS: Abnormality of the RB pathway tended to be more frequent in ICs (60.4%) than in CINs (31.0%) (P = 0.069). The primary target was p16 (CIN, 14.3%; IC, 43.4%; P = 0.032). Abnormality of the p53 pathway was detected in ICs (56.6%) and in CINs (40.5%) (P = 0.1494). In particular, strong expression of MDM2 was higher in ICs (32.1%) than in CINs (7.1%) (P = 0.0045). Abnormalities of the RB and p53 pathways were higher in low-risk and negative HPV than in high-risk HPV (81.3% vs 51.4%, P = 0.0657; 81.3% vs 45.9%, P = 0.0328). Seven HPV-negative cases had abnormalities in the RB or p53 pathways. CONCLUSION: In conclusion, abnormality of the G1 pathway may be one of the important mechanisms for carcinogenesis of low-risk and negative HPV cases.     

Chlamydial cervicitis in women followed-up for human papillomavirus (HPV) lesions of the uterine cervix

To assess the concomitant appearance of Chlamydia trachomatis and Human papilloma virus (HPV) (currently linked with the development of cervical cancer) in uterine cervix, a series of 250 women under continuous observation for cervical HPV lesions (with or without concomitant cervical intra-epithelial neoplasia (CIN)) were the subject of cervical culturing for C. trachomatis, as well as for IP-PAP (indirect immunoperoxidase) staining of the cervical biopsies with monoclonal antibody to C. trachomatis. Chlamydia-positive staining was found in only 2/204 biopsies (0.98%), whereas Chlamydia could be isolated from the cervix of as many as 26/250 (10.4%) women. In repeat cultures, Chlamydia was isolated in 39/936 specimens (4.2%), reflecting the effect of the treatment instituted. The results are discussed in terms of the suggested association of Chlamydia with CIN, as well as of the possible synergism between Chlamydia and HPV in cervical oncogenesis. The conclusion is drawn that Chlamydia and HPV are covariables of sexual behavior, their concomitant appearance in the uterine cervix most probably being ascribable to sexual promiscuity.     

Human papillomavirus (HPV) type distribution in cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in Venezuelan women

Objective

Cervical cancer is an important cause of mortality among women in developing countries, especially in the Latin America and Caribbean (LAC) region. Infection with high-risk (HR) human papillomavirus (HPV) has been identified as the primary cause of cervical cancer. The aim of this study was to determine the frequency of HR-HPV genotypes in low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical carcinoma (CC) among Venezuelan women.

Materials and methods

Subjects with histopathological diagnosis of LSIL, HSIL, and CC (LSIL = 200; HSIL = 100; CC = 150) were enrolled in the study after obtaining informed consent. Biopsy samples of these subjects were analyzed to determine the lesion type. HPV detection and typing was done using polymerase chain reaction (PCR) and reverse hybridization. HPV type specific prevalence was determined in subjects with single and multiple infections.

Results

HPV DNA was detected in 68%, 95%, and 98.7% of LSIL, HSIL, and CC cases, respectively. HR-HPV and low-risk oncogenic HPV (LR-HPV) was observed in 66.9%/11.8% of LSIL cases, 87.3%/3.2% of HSIL cases, and 91.2%/0.7% of CC cases. HPV types -16/-18 (65%) were the most common high-risk HPV types observed, followed by types -52, -33, -45, and -31.

Conclusion

Cervical cancer burden in Venezuelan women is substantial. HPV types -16/-18 were the most common types prevalent among Venezuelan women followed by types -52, -33, -45, and − 31 (prevalence, ~ 90.1%). The results of this study provide baseline information on the HPV type distribution, which may facilitate the development of a cervical cancer prevention and control program in Venezuela.     

Prevalence of sexually transmitted infections (Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and human papillomavirus) in female attendees of a sexually transmitted diseases clinic in Ulaanbaatar, Mongolia

BACKGROUND: Epidemiological data suggest that the prevalence of syphilis, gonorrhea and trichomoniasis has increased in both urban and rural areas of Mongolia. These data are primarily substantiated by notifications of cases of clinically apparent disease in both rural and urban areas, plus laboratory diagnoses from the AIDS/STD Reference Center, Ulaanbaatar. In the past 5 years, however, there has been a marked decline in the total number of patients being screened for sexually transmitted infections (STIs). An assessment of true prevalence of STIs in a female population attending an urban sexually transmitted diseases (STD) clinic was therefore commenced. METHODS: Consecutive women attending an STD clinic in Ulaanbaatar had genital samples collected by the insertion and immediate removal of a tampon, which was then tested for the presence of Neisseria gonorrhoeae, Chlamydia trachomatis, human papillomavirus (HPV) and Trichomonas vaginalis, using polymerase chain reaction (PCR) amplification. RESULTS: A total of 110 women were studied (mean age 26.7 years). Overall, 58 (53%) patients had one or more pathogens identified; 43 (39%) had a single pathogen, while 15 (14%) had mixed pathogens. C. trachomatis was found in 15 (14%), N. gonorrhoeae in 12 (11%), T. vaginalis in nine (8%) and HPV in 39 (36%). Among the 39 HPV-positive patients, oncogenicgenotypes (16, 18, 31, 33, 35, 39, 45, 51, 52) were found in 17(44%) patients. CONCLUSIONS: Sexually transmitted infections as defined by PCR were common, and found in 53% of female attendees of an urban STD clinic in Mongolia. As infections with conventional STIs increase the risk of human immunodeficiency virus (HIV) transmission, it is imperative that strategies be introduced to reduce the prevalence of STIs. Furthermore, detection of oncogenic HPV was common, indicating that it is vital that a strategy to reduce cervical cancer such as a pre-cancer cervical cytology screening program also be introduced.     

Telomerase activity in Papanicolaou smear-negative exfoliated cervical cells and its association with lesions and oncogenic human papillomaviruses

OBJECTIVE: The goal of this study was to evaluate telomerase activity in exfoliated cervical cells and its association with cytology, pathology, and human papillomavirus (HPV). METHODS: Telomerase activity and HPV DNA sequences were examined in the exfoliated cervical cells from a general population of 245 women aged more than 30 years undergoing routine cervical screening by Papanicolaou smear. The women who were found to have telomerase activity or abnormal cytology in their exfoliated cervical cells were examined for cervical lesions by colposcopy and biopsy. RESULTS: Cytology for our population (mean, 56 years) revealed only one abnormal smear (1/245, 0.4%), in which a cervical intraepithelial neoplasia grade I (CIN I) lesion was found. The exfoliated cervical cells used to prepare the smear were negative for telomerase and contained low-risk HPV DNA. Telomerase activity was found in 16 exfoliated cell samples (16/245, 6.5%); high-risk HPV DNA was found in 9 of these samples (9/16, 56%) and 9 of the biopsy specimens that could be evaluated from patients testing positive for telomerase revealed CIN I lesions (9/11, 82%). CONCLUSIONS: Telomerase activity is often associated with high-risk HPV infection and it is suggested that telomerase assay can help to detect occult cervical lesions.     

Chlamydia trachomatis and Human papillomavirus infections in cervical disease in Argentine women

OBJECTIVES: To examine the prevalence of Human papillomavirus and Chlamydia trachomatis DNA in cervical samples among women with normal and abnormal cervical cytology from La Plata, Argentina. METHODS: Two hundred and seventy-nine women (200 with cervical neoplasia or ICC and 79 women with normal cytology) provided cervical samples for the detection of HPV and C. trachomatis DNA by PCR-based assays. RESULTS: HPV DNA increased with the cervical lesion severity, ranging from 30% among women with normal cytology to 99-100% among women with HSIL or ICC. C. trachomatis DNA prevalence increased from low levels in women with normal cytology (11%) to 47% in those with HSIL, but was uncommon among ICC patients (20%). Among women with normal cytology, C. trachomatis prevalence was higher in HPV DNA positive (12.5%) than HPV DNA negative women (10.9%), but this difference was not significant. CONCLUSIONS: HPV prevalence in the general population is slightly higher than those reported for other developing countries. C. trachomatis DNA positivity was associated with a higher risk of both LSIL and HSIL lesions, but not with ICC.     

Factors predicting intermediate endpoints of cervical cancer and exposure to human papillomavirus (HPV) infections in young women screened as potential targets for prophylactic HPV vaccination in south of Brazil

OBJECTIVE: To explore the predictors of intermediate endpoints of cervical cancer in 500 women living in Porto Alegre. STUDY DESIGN: Five hundred randomly selected women (mean age 20.3 years, range 15-25) were screened using PCR detecting 25 HPV types (HPV6, 11, 16, 18, 31, 33, 34, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 68, 70, and 74). Women were interviewed and serum samples were analysed for antibodies to HPV16 and HPV18 VLPs. Regression models were constructed to analyse predictive factors for (a) HPV PCR status, (b) HPV16-seropositivity, (c) HPV18-seropositivity, and (d) SIL in the PAP smear, used as intermediate endpoints of cervical cancer. RESULTS: Specific HPV types were identified in 137 (27.4%) of the 157 (31.4%) PCR-positive women. PAP test result was the most powerful independent predictor of HPV status in PCR (p = 0.0001), followed by the sexual activity started (p = 0.001) (adjusted OR 34.075, 95% CI: 4.650-249.715). PAP test SIL was independently predicted only by the HPV PCR status (p = 0.0001) (OR 7.561, 95% CI: 2.787-20.514). HPV16 and HPV18 serostatus were the most significant predictors of each other (p=0.0001), and the life-time number of sexual partners was more significant (p=0.001) predictor of HPV16 than HPV18 serostatus (p = 0.049). CONCLUSION: These data are useful in evaluating the exposure status of the women to the risk factors of cervical cancer in south of Brazil.     

HPV16 E2基因各区域缺失与宫颈病变相关性的研究

目的:检测湖北地区HPV16阳性宫颈标本E2基因碳端(C)、铰链区(H)、氮端(N)的缺失状态,探讨其与CIN及宫颈癌的关系。方法:将122例宫颈标本按病变程度分为宫颈癌组、CINⅡ~Ⅲ组、对照组。应用多重聚合酶链反应(PCR)将各组HPV16感染标本E2基因的C、H、N分别与E6基因同时扩增,检测E2基因各区域的缺失状态,并应用Scion Image4.0软件半定量分析E2、E6基因条带灰度值,判断HPV DNA的整合状态。结果:宫颈癌组E2基因C、H、N缺失率分别是22.5%,50%,77.5%;CIN组为30.77%,69.23%,92.31%;对照组为9.09%,27.27%,27.27%。E2基因C、H缺失率在3组的任两组间比较无统计学差异(P0.05),而E2基因N端缺失率在宫颈癌组与对照组之间及CIN组与对照组之间差异有统计学意义(P均0.01)。结论:HPV16病毒E2基因N端缺失状态与CIN及宫颈癌有内在关系。在检测HPV感染同时检测E2基因N端缺失状态,对间接判断预后及指导后续治疗有重要意义。     

Evaluation of the Possible Protective Role of Adeno-Associated Virus Type 2 Infection in HPV-Associated Premalignant Disease of the Cervix

Objective. Our objective was to examine the prevalence of adeno-associated virus (AAV) infection in women with normal cervical smears and those with HPV-associated cervical intraepithelial neoplasia (CIN).Methods. HPV typing was performed on DNA from cervical smears of 211 women with CIN (CIN 1 = 83, CIN 3 = 128) and 433 healthy women who had a normal cervical smear. HPV typing was performed on all cases and controls using type-specific oligonucleotide primers (HPV 16, 18, 31, 33). AAV DNA was amplified by nested PCR from the same samples. The amplified DNA were separated on 2% agarose gels, blotted, and hybridized to AAV-2 DNA labeled by random priming with [α-³²P]dCTP to confirm specificity of amplification.Results. A total of 131 cases of CIN were positive for one of the HPV types either alone or in combination. HPV 16 was present in 120 (57%) cases, HPV 18 in 15 (7%), HPV 31 in 27 (13%), and HPV 33 in 15 (7%) and there were multiple HPV types detected in 34 (16%) cases. All of the controls were selected to be negative for HPV. A total of 6/433 (1.4%) control cervical smears and 4/211 (1.9%) of CIN (CIN1 = 2; CIN3 = 2) contained AAV DNA. No correlation between AAV and any clinical feature was observed.Conclusions. These results are different from some that have been previously published and suggest that AAV DNA is not frequently present in either normal control cervical samples or cervical intraepithelial neoplasia. This does not support the hypothesis that AAV may be protective against cervical cancer. Further research is necessary to understand the natural history of AAV infection and its role in human disease.     

已婚女性宫颈上皮细胞中人乳头瘤病毒基因分型2000例分析

目的:探讨江苏省南京地区2000例已婚女性宫颈上皮细胞中23种HPV感染基因型的分布情况。方法:宫颈上皮细胞标本取自江苏省南京市扬子石化集团公司的2000例已婚女性,采用基因扩增及基因芯片技术对其宫颈上皮细胞进行23种HPV基因型别进行检测和分析。结果:2000例已婚女性宫颈上皮细胞标本中检出HPV感染者205例,HPV总感染率为10.25%(205/2000),其中单一型别阳性检出率为8.80%(176/2000)。单一型别感染中HPV43型33例,其阳性检出率为1.65%(33/2000),是最主要的感染型别;其次HPV58型22例,其阳性检出率为1.10%(22/2000)。混合型HPV感染29例,其阳性检出率为1.45%(29/2000);其中HPV16型混合感染占34.48%(10/29),是混合型感染的主要型别;其次是HPV43型混合感染占31.03%(9/29)。29岁以下、30～39岁、40～49岁和50岁以上HPV感染率分别为10.00%、7.24%、11.45%和12.96%。结论:HPV43型、58型单一型别及16型和43型的混合型是感染南京地区2000例已婚女性的主要基因型别,且发病人群呈现低龄化趋势。基因芯片技术可检测出宫颈上皮细胞标本中的多种HPV基因型,对女性宫颈癌的预防及病因学的研究具有重要的作用。     

Herpes simplex virus and human papillomavirus infection in cervical disease in Argentine women.

The aim of the present study was to determine that prevalence of herpes simplex virus (HSV) type 1 and 2 in cervical samples from Argentine women and to assess the role of HSV-2 in cervical cancer. A sample of 79 normal and 200 neoplastic cervical tissues (35 invasive cervical carcinomas, 75 high-grade squamous intraepithelial lesions, 79 low-grade squamous intraepithelial lesions and 11 abnormal squamous cells of undermined significance) was analyzed for herpes simplex and human papillomavirus DNA using the polymerase chain reaction method. Viral genotyping was performed by single strand conformation polymorphisms and restriction fragment length polymorphisms. The overall prevalence of HSV was 21.5% in controls and 29% in cases. Among women with normal cytology, herpes simplex prevalence in HPV positive (20.8%) women was approximately the same as in negative (21.8%) women. HPV- and age- adjusted ORs of high-grade squamous intraepithelial lesions and invasive cervical carcinomas for HSV-2 were 1.4 (p = 0.6) and 1.6 (p = 0.5), respectively. The obtained results indicated that herpes simplex virus may not be involved in cervical cancer development. Future investigations are needed to provided conclusive evidence on the role of this pathogen in cervical cancer.