p53 polymorphism and human papillomavirus infection in Hong Kong women with cervical cancer

In this study we investigated the involvement of p53 polymorphism at codon 72, the infection and typing of human papillomavirus (HPV) and the correlation of p53 polymorphism with HPV type and other clinicopathologic characteristics in 72 Hong Kong women with cervical cancer. We developed a simple and nonradioactive method for determining polymorphism at codon 72 of the p53 gene. The homozygous p53 arginine allele (Arg/Arg) was detected in 22 (31%), the homozygous p53 proline allele (Pro/Pro) in 14 (19%) and the heterozygous allele (Arg/Pro) in 36 (50%) cases, respectively. Using the consensus primers MY11 and MY09, HPV infection was detected in 55 of 72 (76%) cases. The prevalent types were HPV-16 (55%), HPV-18 (16%) and HPV-58 (9%). The number of HPV-positive cases with Arg/Arg, Pro/Pro and Arg/Pro were 17 (31%), 12 (22%) and 26 (47%), respectively. The p53 polymorphism at codon 72 was not significantly correlated with any of the HPV types (p > 0.05). No striking overrepresentation of homozygous arginine-72 p53 was observed in HPV-associated cervical cancer. The results in this study did not show that any p53 polymorphic form has a prognostic significance for cervical cancer.     

Prevalence of human papillomavirus in elderly women with cervical cancer.

To investigate the relation between the prevalence of human papillomavirus (HPV) and age in cervical cancer patients, material from 93 patients with Ia-IIb cervical carcinoma was analyzed for the presence of HPV by both type-specific and general primer polymerase chain reaction. Patients were divided into 2 groups: 64 years or younger, and 65 years and older. There was no statistically significant difference in either the prevalence of HPV DNA or distribution of genotypes amongst the 2 groups. Therefore, HPV detection can be equally well used in the management and follow-up of elderly cervical cancer patients.     

Phenotypic features with p53 alterations related to human papillomavirus and prognostic evaluation in cervical cancer

Cervical cancer is one of the most common tumor affecting women worldwide. Human papillomavirus (HPV) was found to have a causal relationship with cervical cancer and its precursors. The interaction between HPV E6 protein and p53 was identified in in vitro studies. The aim of the study was to evaluate the prevalence of p53 alterations related to HPV infection and the prognostic significance of p53 alterations in cervical cancer. Studies were identified by a MEDLINE search, and all relevant articles were retrieved from 1991 to March 2004. The prevalence of p53 mutations is a rare event in cervical cancer. The correlation between p53 mutations and HPV or prognosis is controversial. Loss of heterozygosity (LOH) of p53 is more commonly found in cervical cancer and is related with the prognosis of this disease. There is no significant correlation between p53 polymorphism and development of cervical cancer. The p53 mutations were not commonly found in cervical cancer. LOH of p53 may contribute to the progression of this malignancy. p53 polymorphism failed to be an independent prognostic factor in predicting the outcome of patients with cervical cancer. Further, epidemiologic surveys should be undertaken in larger populations and in different geographical regions.     

Distribution of human papillomavirus genotypes in women with cervical cancer in Slovenia

Objective

The purpose of the present study was to establish the distribution of human papillomavirus (HPV) genotypes in a representative population of women with cervical cancer in Slovenia in order to contribute to the lacking data on HPV in cervical cancer and to assess the potential local benefit of future prophylactic HPV vaccination.

Study design

A total of 284 samples of cervical cancer were analyzed including archival samples, cervical scrapes and fresh tissue samples. Polymerase chain reaction with GP5+/GP6+ primers was performed in all samples for HPV deoxyribonucleic acid (DNA) detection. All GP5+/GP6+ negative samples were additionally tested using CPI/CPIIg primers and INNO-LiPA HPV genotyping assay.

Results

After exclusion of 6 samples with unsuccessful amplification of beta-globin gene, 262 of 278 cervical cancer samples (94.2%) were HPV DNA positive. HPV genotypes found in the decreasing order of frequency were: HPV 16 (64.9%), HPV 18 (12.2%), HPV 33 (4.7%), HPV 45 (4.1%), followed by HPV 31, 51, 58, 59, 35, 52, 73 and 82 (3.5–0.2%). HPV positive samples were more frequent among squamous cell carcinomas than among adenocarcinomas/adenosquamous carcinomas (95.8% versus 85.5%; P = 0.003). HPV 16 was more frequently found in squamous cell carcinomas than in adenocarcinomas/adenosquamous carcinomas (69.9% versus 37.5%; P < 0.001), while the opposite was true for HPV 18 (6% versus 41.7%; P < 0.001).

Conclusion

Prophylactic HPV vaccination with currently available vaccines could prevent up to 77.1% of cervical cancer in Slovenia, which is caused by HPV 16 or HPV 18.     

Immune responses to human papillomavirus in genital tract of women with cervical cancer

OBJECTIVES: To address a question whether immune responses to HPV infection play a role in control of cervical cancer, we analyzed systemic and mucosal immune responses to HPV in women who underwent radical hysterectomy for cervical cancer (HCC) or loop conization due to cervical dysplasia (LOOP), or had hysterectomy for other reasons (HNN). METHODS: HPV-specific antibodies in sera and vaginal washes were determined by ELISA using recombinant HPV 16 E7 oncoprotein. Cytokines in vaginal washes were assayed by Linco cytokine multiplex method using Luminex technology. Differential gene expression profiling in cervical tumor was determined by microarray analysis and Real-time RT-PCR. RESULTS: While levels of HPV-16 E7-specific IgG in vaginal wash were significantly higher in women undergoing HCC and HNN, the levels of the HPV-16 E7-specific IgA in vaginal wash of women with cervical cancer and cervical dysplasia were lower as compared to patients in HNN. Proinflammatory cytokines, such as IL-6 and IL-8, were dominant in vaginal washes of all subjects studied. However, no pattern of Th1-type and Th2-type cytokine induction was observed as demonstrated by protein analysis as well as differential gene expression profiling in cervical tumor. CONCLUSIONS: These results suggest a selective down-regulation of local HPV-specific IgA responses in women with cervical cancer.     

Prevalence of human papillomavirus genotypes in women with cervical cancer in Papua New Guinea

ObjectiveProphylactic human papillomavirus (HPV) vaccines are currently not available in Papua New Guinea. Prior to introducing these vaccines, knowledge about the HPV genotypes present in cervical cancer in this region is necessary to determine whether the types covered by the 2 commercially licensed vaccines are the same as those in other regions of the world.MethodsFresh, frozen cervical biopsies from 70 women with cervical cancer in Papua New Guinea were collected over a 3-year period from 2006–2009. HPV genotypes were detected using the Genera PapType assay.ResultsOverall, 100% of the specimens were HPV DNA positive, with HPV types 16 and 18 being the most prevalent at 57.1% and 25.7% (95% CI, 0.45–0.68 and 0.17–0.37) respectively, followed by HPV 33 (10%; 95% CI, 0.05–0.19) and HPV 31 (4.3%; 95% CI, 0.01–0.12). Multiple genotypes were identified in 6 women (8.6%), with all biopsies containing HPV 16 and 1 other high-risk type.ConclusionThe 2 most prevalent HPV types identified in women with cervical cancer in Papua New Guinea correspond to global data. This suggests that the currently available HPV vaccines could potentially reduce the burden of HPV-related cervical cancer in Papua New Guinea significantly.     

Detection of human papillomavirus in organs of upper genital tract in women with cervical cancer

In this study, we evaluated the presence of human papillomavirus (HPV) DNA in organs of the female upper genital tract, using nine hysterectomy and salpingo-oophorectomy specimens affected by HPV-positive invasive cervical carcinomas, to establish if cervical HPV infection can spread to upper tracts of the female genital system. HPV DNA was evaluated by polymerase chain reaction (PCR) in all cervical carcinomas as well as in all tracts of the genital system. Then, these data were compared with the results obtained from PCR study of five other hysterectomy and salpingo-oophorectomy specimens (control cases). The criteria used for selection of the control cases were informed consent of the patients for research at the time of surgery, absence of neoplasms, absence of any anatomic lesion caused by HPV in cervix, and external genitalia. All selected cases were squamous cervical carcinomas. PCR analysis revealed HPV DNA in all cases of cervical carcinoma. The HPV DNA was detected as weak positivity on PCR analysis in other organs of the genital system. However, the distribution of HPV DNA varied in the various cases and in the different tracts of the same hysterectomy and salpingo-oophorectomy specimen. We believe that the HPV DNA, detected as a weakly positive signal, in the upper genital tract of patients who have a cervical squamous carcinoma could be a reflection of a latent HPV infection, as well as a sign of the existence of micrometastases containing HPV DNA, which cannot be detected by conventional histologic techniques.     

青岛地区宫颈癌组织中HPV16多态性分析

目的探讨山东省青岛地区妇女宫颈癌组织中人乳头瘤病毒16型（HPV16）上游调控区（URR）和E6基因序列多态性,病毒主要分支,以及他们与宫颈癌的相关性。方法从43例HPV16阳性宫颈癌组织中提取DNA,扩增URR及E6基因,进行序列测定。通过DNASTAR生物软件进行核苷酸和氨基酸序列的分析。结果所有标本URR测序结果均发生了G7521A位点突变;26例（60.5%）宫颈癌组织中检测到核苷酸位点C24T,A7730C和G7842A的联合突变,为另一突变热点。E6测序结果发现突变热点为T178G（D25E）,突变率为65.1%（28/43）;仅1例T350G突变（L83V）。AS型是最多见的病毒突变类型,占65.1%（28/43）,其次为野生型（E-P）23.3%（10/43）。结论青岛地区妇女宫颈癌组织中HPV16URR突变热点为G7521A以及C24T,A7730C和G7842A的联合突变。HPV16E6突变热点为T178G,这些突变热点可能与宫颈癌发生发展有密切关系。AS和E-P原型是青岛地区宫颈癌组织中两种主要的HPV16分支。     

Distribution of human papillomavirus genotypes in archival cervical tissue from women with cervical cancer in urban Sri Lanka

Objective

To identify the contributions of various human papillomavirus (HPV) genotypes in tissue samples from women diagnosed with cervical cancer in Sri Lanka.

Methods

In a retrospective study, archival cervical tissues samples (n = 108) obtained from Sri Lankan women diagnosed with histologically proven invasive squamous cell carcinoma between 2006 and 2007 were tested for HPV. Genotyping of HPV DNA was performed using an INNO-LiPA assay.

Results

Overall, 93% of tumor samples tested positive for HPV DNA. HPV types 16 and 18 accounted collectively for 83.4% of the positive samples.

Conclusion

The findings suggest that the HPV genotypes responsible for causing cervical cancer in Sri Lanka are similar to those reported elsewhere worldwide. Consequently, women in Sri Lanka could benefit from currently available prophylactic HPV vaccines should they be implemented.     

Is human papillomavirus associated with cervical neoplasia in the elderly?

There have been no studies in the United States of human papillomavirus (HPV) in elderly women. This paper presents cross-sectional data on HPV and cervical neoplasia among 232 women age 65 or more. HPV deoxyribonucleic acid (DNA) testing was performed using a modified dot-blot hybridization technique. The prevalence of HPV DNA positivity was 3.5% (95% confidence interval (CI) 0.9%, 6.0%). There were six cases of histologic cervical neoplasia. The crude odds ratio for cervical neoplasia among HPV DNA positives was 18.3 (95% CI 2.8, 120.3). The adjusted odds, controlling for age, prior screening history, current sexual activity, and past contraception use, were 12.2 (95% CI 1.2, 122.9). Ever having had a Papanicolaou smear was protective, and there was a trend for the odds of having neoplasia to increase with age. Additional studies with larger samples of elderly women are needed. If confirmed, the results suggest that, independent of past screening, HPV may increase the risk of having cervical neoplasia for elderly women.     

Genetic polymorphisms of GSTM1, p21, p53 and HPV infection with cervical cancer in Korean women

OBJECTIVES: The aim of this study was to determine whether GSTM1 or GSTT1 might be associated with risk of cervical cancer development in Korean women. The multiplicative interaction of GSTM1 and GSTT1 genotype with p21, p53 polymorphism, and HPV genotype was also investigated. METHODS: From 1997 to 1999, uterine cervical carcinoma was diagnosed in 215 Korean women at the Department of Obstetrics and Gynecology of Seoul National University Hospital. None of the women in the control groups (n = 98) had any evidence of cervical lesions, which were confirmed by Pap smear. Finally, 81 cases and 86 controls were genotyped for p21, p53, and GSTM1 and T1 and HPV infection. A multiplex PCR method was used for the genotyping of GSTM1 and GSTT1; direct sequencing for p53 codon 72, high-risk HPV, and PCR-RFLP (BsmAI) for p21 codon. The unconditional logistic regression analysis was used to calculate ORs and 95% CI. RESULTS: Although the GSTM1 and GSTT1 genotype was not significantly associated with cervical cancer development for all women, the GSTM1 null genotype was significantly associated with an increased risk of cervical cancer development in women with high-risk HPV infection (OR = 2.9, 95% CI: 1.0-8.2). Although the frequency of overall GSTT1 null genotype was significantly lower in cervical carcinoma patients with high-risk HPV infection (OR = 0.3, 95% CI: 0.1-1.0), almost 2-fold increased risk was observed among women with GSTT1 null and Arg/Arg genotype (OR = 1.9, 95% CI: 0.7-5.4). Although the cervical cancer risk was 3.3-fold increased in women with null and Arg/Arg genotype compared to women with GSTM1 present and p21 Ser-containing genotype, there was no significant multiplicative interaction between GSTM1 and p21 (P for interaction = 0.785) or p53 (P for interaction = 0.815). CONCLUSIONS: These findings suggest that the risk of cervical cancer may be related to GSTM1 genotype in women with high-risk HPV infection and that there is a possible gene-gene interaction in the incidence of cervical cancer.     

Prevalence of human papillomavirus infection and correlation with cervical lesions in Japanese women

PURPOSE: To investigate the prevalence of human papillomavirus (HPV) infection in patients attending a gynecologic outpatient department, and to correlate the infection status with the presence or absence of uterine cervical lesions and the grades assessed by cytological or histological examinations. METHODS: Five hundred and seventy-two subjects were studied. In all subjects, HPV detection by the hybrid capture method and a cervical cytological examination were performed RESULTS: The HPV-positive rate in subjects with normal cytology was 12.3%. The detection rate was high (21.7%) in subjects aged in the twenties and low in the forties, and HPV was not detected in subjects aged in the sixties and seventies. When HPV-positive rates were examined according to cytological or histological grades, the rates were higher in subjects with abnormal cytology (P < 0.01) or cervical intraepithelial neoplasia (CIN) or squamous cell carcinoma compared with those with normal cytology. CONCLUSION: Diagnosis of HPV infection is also important for the prediction of progression to CIN and cervical cancer.     

Transduction of adenovirus-mediated wild-type p53 after radiotherapy in human cervical cancer cells

OBJECTIVE: Radiotherapy is the mainstay of treatment for advanced cervical cancer and most cervical cancers have evidence of HPV (human papilloma virus) infection, which inactivates the p53 gene. The goal of this study was to determine the effect of combining radiotherapy and Adp53 infection on the growth of cervical carcinoma cells. METHODS: The silta cervical carcinoma cell line contains wild-type p53 and HPV 16 infection. The C33A cell line has a p53 mutation. The Adp53 recombinant adenovirus contains the cytomegalovirus promoter, wild-type p53 cDNA, and a polyadenylation signal in a minigene cassette inserted into the El-deleted region of a modified adenovirus 5. Transduction efficiency was assessed by using an adenovirus containing the Escherichia coli beta-galactosidase gene and expression of wild-type p53 in infected cells was evaluated by Western blot analysis. One group of cells was irradiated prior to infection, the other group received no irradiation, but were either infected with virus or mock-infected. Cells were analyzed for viability 1 to 7 days after infection by using the sulforhodamine B assay. The percentage of cells undergoing apoptosis was determined by using a TUNEL assay. RESULTS: Fifty percent of C33A cells were transduced with 5 muthplicities of infection of virus whereas SiHa cells required 25 multiplicities of infection. Adp53 expression was found 48 h after infection. In the cells treated with both radiation and Adp53 infection growth inhibition was increased compared with inhibition resulting with either treatment alone. The combination treatment also increased the percentage of cells undergoing apoptosis. CONCLUSION: Combining radiotherapy with Adp53 infection increases the inhibition of growth of cervical cancer cells in vitro. This combination treatment has the potential of increasing efficacy and of therapy.     

Advances in cervical cancer screening and human papillomavirus vaccines

Cervical cancer is causally linked to human papillomavirus (HPV) and constitutes a major health problem for women. Nearly 80% of the 510,000 cases reported worldwide each year occur in developing countries which lack organized screening programmes. Cervical screening has effectively reduced the incidence of and mortality from invasive cervical cancer in industrialized countries, but is not completely protective. Cervical screening is now undergoing modernization and has seen several changes in recent years. These aim to enhance the overall efficiency and effectiveness of screening, reduce rates of inadequate sampling, increase sensitivity rates and facilitate ancillary technologies, such as HPV testing. This review discusses these advances and the development of HPV vaccines.