HPV oligonucleotide microarray-based detection of HPV genotypes in cervical neoplastic lesions

BACKGROUND: In this study we examined the use of a new-human papillomavirus (HPV) detection method, the HPV oligonucleotide microarray system (Biomedlab Co., Korea), which we compared with the well-established HPV DNA detection system (Hybrid Capture II; HC-II, Digene Co.). This new method prompted us to develop a new HPV genotyping technique, using the oligonucleotide microarray, to detect the generic and type-specific sequence of HPV types. In particular, we undertook the evaluation of the clinical efficacy of the HPV oligonucleotide microarray for detecting HPV in cervical neoplastic lesions. METHODS: One hundred forty patients were involved and classified into three groups according to their histopathologic diagnoses: Group I (nonspecific chronic cervicitis; n = 61), Group II (low-grade squamous intraepithelial lesion (SIL); koilocytosis, and mild dysplasia; n = 39), and Group III (high-grade SIL; moderate, severe dysplasia and in situ carcinoma; n = 40). Cytological diagnoses were based on the Bethesda System and cervical samples were analyzed by the two methods. The HPV oligonucleotide microarray detected 15 types of high-risk HPV (HPV-16/-18/-31/-33/-35/-39/-45/-51/-52/-56/-58/-59/-66/-68/-69) and 7 types of low-risk HPV (HPV-6/-11/-34/-40/-42/-43/-44). RESULTS: In 105 of the 140 cervical samples (75%), HPV DNAs were examined using the HC-II method. HPV detection rates using the HPV microarray agreed with those of HC-II. One HC-II-positive, but HPV microarray-negative, case occurred in the low-grade SIL (Group II) and was later confirmed negative for HPV. The other HPV microarray-positive but HC-II-negative case was found to be HPV-18 by PCR. Low-risk types of HPV were detected in 3 of 39 low-grade SIL cases (Group II) using the HPV microarray. HPV-16 was the most frequent type (32.1%) in all specimens tested, and was significantly more frequent in low-grade or high-grade intraepithelial lesions (Groups II or III) than in normal controls (Group I) (P < 0.05). HPV-58 was the second most common type (17.5%) in Group III. The HPV microarray was found to have advantages in terms of identifying the HPV genotypes and cases of multiple HPV infection. Double HPV infections were detected in 12 cases and triple HPV infections in 7 cases. Two cases were positive for four types of HPV (HPV-16/18/33/35, HPV-16/18/58/68). The sensitivity of HPV testing (HC-II; 94.9%, HPV microarray; 93.7%) for identifying patients with squamous intraepithelial lesion was significantly better than the sensitivity of cytology (77.1%, P < 0.05). On using multiple logistic regression analysis to estimate the relative risk of SIL versus HPV type, HPV-16-positive cases were found to have a 7.5-fold risk of SIL (95% CI = 3.28-16.51; P < 0.01). HPV-33 and HPV-58 were found to be significantly related to high-grade SILs (P < 0.01). CONCLUSIONS: Our results suggest that the HPV oligonucleotide microarray is highly comparable to HC-II for detecting HPV in cervical specimens. The HPV oligonucleotide microarray provides useful information on viral genotype and multiple HPV infections in HPV-related cervical lesions. Genetic information on HPV in cervical specimens might be a particular benefit of the new procedure in the management of cervical neoplastic lesions     

Detection of HPV genotypes in cervical lesions by the HPV DNA Chip and sequencing

OBJECTIVE: A newly introduced HPV detection technique in cervical lesion, the HPV DNA Chip test, contains 24 HPV probes and has the advantage of being able to detect 24 HPV types at once. We performed HPV DNA sequencing and compared the results with that of the HPV DNA Chip for evaluation of the accuracy of the DNA Chip test. METHODS: The HPV DNA sequencing was performed in samples of 282 patients, where specific HPV type had been shown in HPV DNA Chip test. The sixteen cases where multiple HPV types had been found in HPV DNA Chip test were included in 282 cases. The sequencing was also performed in HPV-other type samples of 95 patients, where positive in HPV-PCR, but specific HPV type had not been found. RESULTS: In 257 cases (91.1%) of 282 cases, the HPV types of the HPV DNA sequencing test were in agreement with types of the HPV DNA Chip. In 16 cases (5.7%), the sequencing types were different from the types of HPV DNA Chip. But, in 9 of 16 cases, types in HPV DNA sequencing were absent types in HPV DNA Chip test. The interpretation of HPV DNA sequencing was impossible in nine cases (3.2%). The HPV DNA sequencing test of 95 cases of HPV-other type showed that the sequencing types from 94 cases (98.9%) were absent types in HPV DNA Chip test. In sequencing test of HPV-other type, HPV-81 (20.0%), HPV-62 (14.7%), HPV-84 (13.7%), and HPV-61 (13.7%) were frequently detected. CONCLUSION: HPV DNA Chip is an accurate method for detecting the 24 HPV genotypes.     

Good correlation of HPV DNA test between self-collected vaginal and clinician-collected cervical samples by the oligonucleotide microarray

OBJECTIVES: To evaluate the efficacy of self-collected vaginal samples for high-risk HPV detection by the HPV oligonucleotide microarray method (HPVDNAChip). METHODS: One hundred and eighteen patients with abnormal Pap smears were included. Self-collected vaginal and clinician-collected cervical samples for HPV testing were obtained. The result of the HPV DNA test was compared with the histopathological diagnosis or colposcopic finding. RESULTS: Of the 118 patients, 42 (35.6%) had >or= cervical intraepithelial neoplasia (CIN) III lesions. Using the HPVDNAChip, high-risk types of HPV were detected in 38 of these 42 patients (90.5%) with the self-collected vaginal samples and in 37 of 42 (88.1%) with the clinician-collected cervical samples. The agreement of HPVDNAchip results between self- and clinician-collected samples was very good (kappa = 0.81) with a 93.2% concordance rate. Multiple HPV infections were found in 17 of 88 (19.3%) HPV-positive clinician-collected cervical samples. The rate of multiple HPV infection tended to decrease as the degree of pathologic classification increased. CONCLUSION: Using the HPVDNAchip to assay for HPV infection, results from self-collected vaginal samples were compatible with those from clinician-collected cervical samples.     

HPV16/18 prevalence in cervical lesions/cancers and p53 genotypes in cervical cancer patients from India

OBJECTIVES: The HPV16/18 code for an oncoprotein-E6, which binds to p53 tumor suppressor protein and degrades the protein via ubiquitination. A common polymorphism of p53 in exon 4 codon 72, resulting in either proline (Pro) or arginine (Arg), affects HPV16/18 E6-mediated degradation of p53 protein in vivo. Hence, in the current study we investigated the prevalence of HPV16/18 in cervical lesions and the distribution of p53 genotypes in cervical cancers and normal healthy women. METHODS: DNA from 337 Indian women with invasive cervical cancers, 164 women with clinically normal cervix, 64 women with low-grade squamous intraepithelial lesions (LSIL), and 5 women with high-grade squamous intraepithelial lesions (HSIL) was examined for the presence of HPV16/18 using consensus primers in a polymerase chain reaction (PCR), and the specific HPV type was identified by Southern hybridization of the PCR product using HPV16/18 type-specific nucleotide sequences as probes. Further, 134 women with cervical cancers and 131 healthy women were used to determine the frequency of p53 genotypes, Pro/Pro, Arg/Arg, and Pro/Arg, using peripheral blood cell DNA to indicate the constitutional genotypes and allele-specific primers, in a PCR-based assay. RESULTS: We observed a prevalence of HPV16/18 in 77% (258/337) of cervical cancer patients, 38% (24/64) of LSILs, 4 of 5 HSILs, and 15.2% (25/164) of normal healthy women. The frequency of distribution of the three genotypes of p53 codon 72 in a subgroup of the HPV16/18-positive cervical cancer patients was Pro/Pro 0.18 and Arg/Arg 0.26, with the heterozygous Pro/Arg 0.56, differing significantly from the genotype frequency in the normal healthy women (chi(2) = 6.928, df = 2, P < 0.05). CONCLUSIONS: A high prevalence of HPV16/18 was observed in the cervical cancers. The prevalence in LSILs confirms HPV16/18 infection as an early event and further indicates a role in progression of lesions. The p53 genotype distribution indicated that women homozygous for Arg genotype were at a 2.4-fold higher risk for developing HPV16/18-associated cervical carcinomas, compared to those showing heterozygous Pro/Arg genotype (odds ratio 2.4, 95% confidence interval 1.89 to 3.04).     

Age distribution of HPV genotypes in cervical intraepithelial neoplasia

Objective

Recent data showed that HPV16 infections in young women can lead to CIN3 formation very quickly and questioned the common assumption that invasive cervical cancer develops through slowly progressing pre-cancer lesions, CIN1, CIN2 and CIN3. The aim of the study is to compare the age distribution of HPV 16/18 related and HPV16/18 not related CIN.

Methods

We used the data generated from the clinical use of HPV genotyping (LINEAR ARRAY, Roche Diagnostics). Patients were grouped on the basis of histology, CIN1 vs. CIN2+ and on HR-HPV genotype status.

Results

The probability to develop a CIN2+ seemed to decrease with age in patients infected with HR-HPV genotype 16/18 while the inverse effect was observed in CIN2+ patients who were HR-HPV positive but HPV16/18 negative (Chi-square test, p^trend = 0.01). Only in HR-HPV positive but HPV 16/18 negative patients, a relative reduction of CIN1 vs. CIN2+ was observed with increasing age (Cochran-Armitage test, p^trend = 0.01); finally, in HR-HPV non-16/18 infected patients only a statistically significant difference in mean age between CIN1 and CIN2+ patients below age 35 was observed.

Conclusions

Besides the limitations of the present cross-sectional analysis, these data suggest a genotype specific natural history of cervical cancer precursors development: one type, more frequent, HPV16/18 related, which develops quick and early in life; another one, non-16/18 HR-HPV related, which develops later, slowly, through low- to high-grade lesions. If confirmed, this hypothesis could influence screening policies, especially in the vaccinated population.     

Detection of HPV DNA in the uterine cervical lesions by polymerase chain reaction and in situ hybridization]

Human papillomavirus (HPV) is found in close association with carcinogenesis of the uterine cervix. We applied a new in vitro gene amplification technology, the polymerase chain reaction (PCR) to detect HPV 16 and 18 in cervical exfoliated cells. HPV infections were detected in 5 (16%) of 31 women with no pathological lesions of the uterine cervix (normal), 16 (24%) of 67 with cervical intraepithelial neoplasia (CIN) and 6 (38%) of 16 with invasive cervical cancer. Moreover, 10% formalin-fixed and paraffin-embedded tissue sections were prepared from the uterine cervix of these 27 women with PCR-proven HPV infection and were examined for the histological localization of HPV-DNA by in situ hybridization with biotin-labeled DNA probes of HPV types 6/11, 16/18 and 31/33/35. HPV-DNA type 16/18 was detected in 3 of 5 normal women, 2 of 4 CINs I, 2 of 3 CINs II, 6 of 9 CINs III and 6 of 6 invasive cervical cancers. HPV-DNA type 6/11 was detected in 6 of 6 condylomas. Viral DNA sequence was detected in the superficial cells of CIN I and II, and it was distributed through entire thickness layer of undifferentiated cells derived from CIN III and squamous cell carcinoma. In addition, the staining intensity became weak as the lesion progressed. These differences between lesions might be due to the difference in the viral form in the nuclei, ie whether an episomal or integrated form. Thus, an in situ hybridization technique with a biotin-labeled DNA probe as well as the PCR method is useful for the detection of HPV in clinical samples.     

HPV L1壳蛋白联合HR-HPV分型、TCT检测对宫颈癌前病变及宫颈癌的诊断价值分析

目的探究人乳头瘤病毒L1(HPV L1)壳蛋白联合高危型HPV(HR-HPV)分型、液基薄层细胞学(TCT)检测对宫颈癌前病变及宫颈癌的诊断价值。方法选取2018年5月至2020年2月在西安交通大学第一附属医院接受宫颈癌筛查的妇女1094例为对象,以组织病理学检查结果进行分组,比较各组HPV L1壳蛋白表达水平、HR-HPV和TCT检测阳性率。结果TCT检测阳性率与HR-HPV阳性率存在明显差异(P<0.05)。组织病理学检查,共检出正常或炎症179例(对照组)、CIN 1组26例、CIN 2组44例、CIN 3组40例和宫颈癌组21例,宫颈癌组的TCT检测阳性率和HR-HPV阳性率最高,HPV L1壳蛋白表达水平最低(P<0.05)。HPV L1壳蛋白联合HPV分型、TCT检测诊断宫颈癌前病变及宫颈癌的AUC值分别为0.897和0.804(P<0.05)。结论HPV L1壳蛋白、HPV分型和TCT检测在宫颈癌前病变及宫颈癌的诊断中具有一定的临床价值。     

HPV L1壳蛋白联合HR-HPV分型、TCT检测对宫颈癌前病变及宫颈癌的诊断价值分析#br#

Objective? To explore the diagnostic value of human papilloma virus L1 (HPV L1) capsid protein combined with high-risk HPV (HR-HPV) typing and thinprep cytology test (TCT) for cervical precancerous lesions and cervical cancer. Methods?1 094 women who received cervical cancer screening were selected as the research subjects, and were grouped based on histopathological results. The expression level of HPV L1 capsid protein, and positive rates of HR-HPV and TCT were compared between the groups. Results?There was a significant difference between TCT positive rate and HR-HPV positive rate (P<0.05). Histopathological examination found 179 normal cases or cases only with inflammation (control group), 26 cases of CIN gradeⅠ (CIN1 group), 44 cases of CIN gradeⅡ (CIN2 group), 40 cases of CIN gradeⅢ (CIN3 group) and 21 cases of cervical cancer (cervical cancer group). The positive rates of TCT and HR-HPV in cervical cancer group were the highest, and the expression level of HPV L1 capsid protein was the lowest (P<0.05). The AUC values of HPV L1 capsid protein combined with HPV typing and TCT to diagnose cervical precancerous lesions and cervical cancer were 0.897 and 0.804, respectively (P<0.05). Conclusion?HPV L1 capsid protein, HPV typing and TCT are of clinical value in the diagnosis of cervical precancerous lesions and cervical cancer.     

Human papillomavirus (HPV) genotyping by HPV DNA chip in cervical cancer and precancerous lesions

OBJECTIVES: The human papillomavirus (HPV) is a well-known cause of cervical cancer. HPV tests are used as an adjunct test to decrease the false-negative rate of cytological screening. However, attempts are being made to replace the cytological screening with HPV tests. Therefore, this study was performed to examine the possibility of using HPV tests as screening test. MATERIALS AND METHODS: The results of the tests that were performed at the same time including the ThinPrep cytology, the high-risk group hybrid capture II (HC-II) test, the HPV DNA chip (HD-C) test, and a punch biopsy were compared in 400 women who were referred to us due to abnormal cytology or cervicogram. The accuracy of each test was then evaluated, and the type of virus was investigated using a HD-C test. RESULTS: The positive predictive values detected by the high-risk group HC-II test and HD-C test according to the histological diagnosis outcomes were 56.8 and 53.8%, respectively, for cervicitis; 91.5 and 91.5%, respectively, for cervical intraepithelial neoplasia I (CIN I); 88.1% and 81.0%, respectively, for CIN II; 88.6 and 84.2%, respectively, for CIN III, and 92.5 and 88.7%, respectively, for cancer (in 53 patients). The most prevalent types of HPV according to the HPV tests were types 16, 58, 18, and 52 in which type 16 was detected in the more advanced lesions. The sensitivity was 88.4% for the ThinPrep cytology, 89.9% for the HC-II for the high-risk group, and 86.2% for the HD-C test. CONCLUSION: These results suggest the possibility of using the HC-II and HD-C tests as screening tests, which have a similar sensitivity as the ThinPrep cytology. Nonetheless, randomized controlled trials will be needed before the actual application of the HPV tests as screening tests. Despite the fact that the importance of HPV type 16 in cancer development was confirmed, the prevalence of types 58 and 52 were relatively high compared with those found in other studies, showing a need for further studies on this subject. These HPV types need to be considered in vaccine development.     

子宫颈上皮癌变过程中Ki67表达和HPV感染的研究

目的 研究Ki67表达和HPV感染在宫颈癌发生发展过程中的意义。方法 分别从正常宫颈(10例)、各级CIN(CIN Ⅰ19例,CIN Ⅱ9例,CIN Ⅲ16例)和宫颈鳞癌(8例)的石蜡标本提取基因组DNA,选取HPV L1区通用引物进行PCR扩增,测序,与已知HPV序列进行同源性分析。Ki67免疫组化染色。结果 正常宫颈组HPV DNA均为阴性。CIN Ⅰ组5/19例为高危型HPV(16/18型),8/19例为中危型(35型等),其余为低危型。CINⅡ和Ⅲ组高危和中危型HPV各占一半。宫颈癌组均为高危型,绝大部分为HPV16。Ki67指数随CIN级别的升高(CINⅠ:21.4±1.1,CINⅡ:31.8±3.5 CINⅢ:61.3±2.8)而明显增加(P<0.01)。结论Ki67指数反映出在宫颈上皮细胞癌变过程中细胞增殖活性的改变。HPV型别与CIN级别及转归密切相关。Ki67与HPV检查联合应用对评价CIN细胞增殖活性及其转归有重要的作用,对伴有HPV16/18 感染的CIN应密切追踪和积极处理。     

The p53 codon 72 genotypes in HPV infection and cervical disease

OBJETIVE: An experimental study has indicated that individuals homozygous for the Arg-encoding allele of p53 gene may have an increased susceptibility to HPV-related cervical cancer but many epidemiological studies have failed to repeat this result. Many epidemiological studies have failed in the attempt to repeat this results. The aim of the present work was to investigate whether the p53 arginine allele confers a risk factor for cervical carcinogenesis. STUDY DESIGN: Using PCR based technology, DNAs from 90 normal cervical samples and 205 abnormal cervical tissue scrapes were analyzed for the type of HPV present and p53 codon 72 polymorphism. RESULTS: Non statistically significant differences were found for the frequencies of p53 genotypes in the different cytological/histological groups (chi2=1.4; P=0.97) nor for the risk for HPV infection (chi2=1; P=0.9). CONCLUSION: This study showed that polymorphism at codon 72 of TP53 gene is not associated with an increased susceptibility to cervical disease and/or HPV infection in the Argentine women population.     

阴道微生态变化与宫颈人乳头瘤病毒感染及相关病变的关系

阴道微生态的变化或失调会导致阴道炎症的发生,阴道p H值是评价阴道微生态方便、快捷的指标。阴道p H升高时,宫颈HPV感染显著增加,多型别HPV感染率也增加,并且宫颈及阴道HPV感染引起的宫颈低度鳞状上皮内病变(LSIL)发生率升高。BV是最常见的阴道感染,其明显增加了宫颈HPV的感染风险;性传播性疾病病原体引起的感染(STI)的女性宫颈HPV感染的发生率较高;有研究提示,阴道假丝酵母菌感染、阴道滴虫感染与HPV感染无明显相关性。常见的阴道感染对宫颈病变的影响无肯定结论。     

HPV感染年龄与高度宫颈上皮内瘤变的关系

目的探讨高危型人乳头瘤病毒（HR-HPV）感染患者年龄分布与高度宫颈上皮内瘤变和宫颈癌的关系。方法 2008年7月至2009年4月在中日友好医院同时采用液基薄层细胞学（LCT）和HPV检测行宫颈癌筛查的妇女948例,对LCT≥ASC-US和/或HR-HPV阳性的367例患者进行阴道镜下宫颈活检。结果 〈50岁年龄组妇女的HR-HPV感染率（34.27%）与≥50岁年龄组妇女（18.98%）比较,差异具有统计学意义（P〈0.01）;〈30岁、30～49岁和≥50岁3个年龄组HR-HPV阳性者中,≥CIN2患者的例数分别为18例（39.13%）、81例（43.78%）和17例（32.69%）,差异无统计学意义（P〉0.05）。结论各个年龄段感染HR-HPV的妇女发生≥CIN2的机会无明显差异,均应加强随访。     

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.     

宫颈癌及上皮内瘤变人乳头瘤病毒基因型的检测

目的:了解宫颈癌及上皮内瘤变人乳头瘤病毒(HPV)的感染率及其基因型的分布。方法:用PCR-RFLP法检测239例宫颈癌及上皮内瘤变患者HPV感染并进行分型。先用PGMY09/11共同引物扩增生殖道粘膜型HPV L1区的高度保守区,然后联合使用RsaⅠ、MseⅠ、PstⅠ和HaeⅢ4个限制性内切酶对阳性PCR产物进行酶切,利用不同的酶切片段鉴定HPV的基因型。结果:在239例宫颈癌及上皮内瘤变患者中共检出205例(85·8%)HPV感染,其中宫颈上皮内瘤变Ⅰ级(CINⅠ)、宫颈上皮内瘤变Ⅱ~Ⅲ级(CINⅡ~Ⅲ)和宫颈癌中HPV感染率分别是66·7%,89·9%和98·3%,差异有统计学意义(P<0·001)。在宫颈癌及上皮内瘤变中共检出22型HPV,其中主要基因型及其感染率分别是HPV16(45·6%)、58(12·1%)和52(6·3%)。结论:宫颈癌及上皮内瘤变中HPV感染的基因型至少可达22型,其中以HPV16、58和52为最常见。     

患宫颈病变的维、汉族妇女高危型HPV分型比较研究

目的探讨人高危型乳头瘤病毒（HPV）在维吾尔族宫颈炎,宫颈癌前病变,宫颈癌中的分布及意义。方法应用Hybrimax基因芯片导流杂交技术,对2011年11月至2012年10月在新疆维吾尔自治区人民医院就诊的HC2结果阳性的428位维吾尔族及汉族妇女的宫颈细胞标本进行HPV基因型分型检测。结果 HPV16型在维吾尔族及汉族妇女在慢性宫颈炎,宫颈癌前病变和宫颈癌等不同病变比较中,差异具有统计学意义（P〈0.05）,但是两民族间的分布差异无统计学意义（P〉0.05）。HPV感染在两个民族同样是以单一感染为主,其中HPV16型单一感染最多。除HPV16、18型外,维吾尔族妇女全部宫颈脱落细胞中（宫颈炎、癌前病变及宫颈癌）常见亚型检出次数依次为HPV52、53、58、39、68,31、66、56、6和11型。汉族妇女为HPV52、58、53、31、33、68、66、39、45、11、6和CP8304型。结论 HPV16型感染是维、汉妇女正常宫颈、癌前病变及宫颈癌中常见的型别,同时随着病变进展所占比例增加,两个民族间分布差异无统计学意义（P〉0.05）;除HPV16、18型以外,高危型HPV52、58型在维、汉妇女各级别病变中最多见。维、汉妇女宫颈各病变中HPV感染以单一感染为主,两个民族妇女癌前病变及宫颈癌以HPV16型单一感染为最多见。     

Precancerous lesions and cervical cancer vs HPV infection in pregnant women--cytological assessment

An effort has been made in order to estimate the relationship between HPV, cervical intraepithelial neoplasia and cervical carcinoma. The authors have been trying also to create a reliable prophylactic scheme as far as precancerous lesions and cervical carcinoma are concerned. 2243 pregnant women have been subjected to cytology and colposcopy examination. In selected cases HPV DNA hybridisation technique examination of cervical smear as well as colposcopy directed punch biopsy have been performed. The results of the study indicate of high efficiency of these methods in cervical cancer prophylaxis.     

The impact of anti HPV vaccination on cervical cancer incidence and HPV induced cervical lesions: consequences for clinical management

Cervical cancer is the second most common cause of cancer-related deaths in women worldwide. Screening for cervical cancer is accomplished utilizing a Pap smear and pelvic exam. While this technology is widely available and has reduced cervical cancer incidence in industrialized nations, it is not readily available in third world countries in which cervical cancer incidence and mortality is high. Development of cervical cancer is associated with infection with high risk types of human papillomavirus (HPV) creating a unique opportunity to prevent or treat cervical cancer through anti-viral vaccination strategies. Several strategies have been examined in clinical trials for both the prevention of HPV infection and the treatment of pre-existing HPV-related disease. Clinical trials utilizing prophylactic vaccines containing virus-like particles (VLPs) indicate good vaccine efficacy and it is predicted that a prophylactic vaccine may be available within the next five years. But, preclinical research in this area continues in order to deal with issues such as cost of vaccination in underserved third world populations. A majority of clinical trials using therapeutic agents which aim to prevent the progression of pre-existing HPV associated lesions or cancers have shown limited efficacy in eradicating established tumors in humans possibly due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Future trends in clinical trials with therapeutic agents will examine patients with early stage cancers or pre-invasive lesions in order to prevent invasive cervical cancer. Meanwhile, preclinical studies in this field continue and include the further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. Given that cervical cancers are caused by the human papillomavirus, the prospect of therapeutic vaccination to treat existing lesions and prophylactic vaccination to prevent persistent infection with the virus are high and may be implemented in the near future. The consequences for clinical management may include a significant reduction in the frequency of Pap smear screening in the case of prophylactic vaccines, and the availability of less invasive and disfiguring treatment options for women with pre-existing HPV associated lesions in the case of therapeutic vaccines. Implementation of both prophylactic and therapeutic vaccine regimens could result in a significant reduction of health care costs and reduction of worldwide cervical cancer incidence.