Human papillomavirus DNA sequences and p53 over-expression in laryngeal squamous cell carcinomas in Northeast China

One-hundred-two patients with laryngeal squamous cell carcinomas in Northeast China were examined for human papillomavirus (HPV) DNA by the polymerase chain reaction (PCR) coupled with Southern blot hybridization, and for p53 over-expression by immunohistochemical staining. HPV DNAs were found in 60 cases (58.8%). HPV-16, -18, -6, -11, and -33 DNAs were detected in 30 cases, 22 cases, 25 cases, two cases, and one case, respectively. In addition, coinfection either with HPV-6 and -16 or with HPV-6 and -18 was detected in 20 cases (33.3% of HPV DNA-positive cases). p53 over-expression was observed in 60 patients (58.8%). p53 was over-expressed significanty in the poorly-differentiated SCC and in patients with metastasis to lymph nodes (P < 0.05, respectively). Both HPV DNA and p53-expression were positive in 35 patients, and negative in 17 patients. Either HPV DNA or p53-expression were positive in 50 patients (25 cases each). Although p53 was detected in 35 (58.3%) of HPV-positive patients, there was no significant correlation between HPV infection and p53 over-expression in laryngeal squamous cell carcinomas of Northeast China. J. Med. Virol. 54:186–191, 1998. © 1998 Wiley-Liss, Inc.     

Adenocarcinoma of the uterine cervix in Ireland and Sweden: human papillomavirus infection and biologic alterations.

Paraffin-embedded samples from cervical adenocarcinomas, 19 cases from Irish patients and 19 cases from Swedish patients, were analyzed by polymerase chain reaction for the presence of infection with human papillomavirus (HPV). The results were compared with DNA ploidy, proliferation activity, and p53 and p21/WAF1 expression. The studies were performed to discover whether high-risk HPV infection in adenocarcinomas of the uterine cervix is associated with an increased proliferative activity and genomic instability. The results show that the majority (84.6%) of patients 59 years of age or younger showed HPV infection. The overall prevalence of HPV DNA was 60.5%, with the high-risk types, 16 and 18, the most frequent. HPV-16 had a prevalence of 23.7% (9 of 38), and HPV-18 had a prevalence of 26.3% (10 of 38). The HPV-positive tumors predominantly showed a tetraploid DNA distribution pattern, whereas HPV-negative tumors more frequently showed highly scattered aneuploid DNA profiles. Both HPV-positive and HPV-negative cases displayed high proliferative activity, as indicated by high Ki-67 and cyclin A immunoreactivity. Tumor suppressor gene analysis detected low p53 expression and high p21/WAF1 expression in HPV-positive patients and high p53 expression without simultaneously increased p21/WAF1 (indicative of mutated p53) in HPV-negative cases in the groups of women older than 59 years of age.     

人乳头瘤病毒与P 53协同致膀胱移行细胞癌关系的研究

目的 研究人类乳头瘤病毒（ＨＰＶ）６、１１、１６和１８型及Ｐ５３与膀胱移行细胞癌的关系。方法 采用聚合酶链反应（ＰＣＲ）方法检测了７５例膀胱移行细胞癌组织中ＨＰＶ的感染,免疫组化ＳＰ法检测Ｐ５３蛋白表达情况。结果 膀胱移行细胞癌组织中ＨＰＶ６、１１、１６和１８的阳性率分别为６．７％（５／７５）,５．３％（４／７５）,３３．３％（２５／７５）和６．７％（５／７５）。低危型ＨＰＶ（６或１１）阳性率为９．３％（７／７５）,高危型ＨＰＶ（１６或１８）阳性率为３４．７％（２６／７５）。同一膀胱癌组织中两种以上（包括两种）ＨＰＶ亚型感染８例,占１０．６％。ＨＰＶ６、１６和１８型之间感染阳性率在肿瘤有无转移组中差异显著（Ｐ〈０．０５）,ＨＰＶ１６、１８的阳性率在肿瘤病理分级中差异有极显著性（Ｐ〈０．０１）。ＨＰＶ ＤＮＡ型别     

The expression of P53 protein and infection of human papilloma virus in conjunctival and eyelid neoplasms

Human papilloma virus (HPV) infection and loss of P53 function have been identified as frequent events in various human tumors. The aim of this study was to evaluate P53 protein expression and to detect HPV in the tissue samples of 45 benign (papillomas) and 38 malignant conjunctival and eyelid lesions (27 basal cell carcinomas and 11 squamous cell carcinomas). We also looked for eventual relationships between P53 expression and clinicopathological features such as age, histological type of tumor, grading and staging. HPV infection was detected using the PCR-RFLP method. Specific primers were engaged and PCR products of HPV 16, 18, and 33, underwent enzymatic digestion at 37 degrees C. We revealed P53 protein expression in 30 out of 45 (66.6%) squamous cell papillomas. In the SCC and BCC groups, P53 was present in 31 out of 38 carcinomas and there was a statistically significant correlation between histological type of tumor and P53 protein expression. Malignant type HPV 16 and 18 were detected in three squamous cell papillomas, two BCCs and one SCC. However, we observed P53 protein expression in only two HPV-positive papillomas and one infiltrative type of BCC. P53 is probably involved in the development of conjunctival and eyelid tumors due to its high rate of presence in both benign and malignant neoplasms of these organs. HPV seems to occur rarely. In some cases its role in the pathogenesis of conjunctival and eyelid tumorigenesis should be considered as auxiliary.     

Detection of human papillomavirus DNA in fine-needle aspirations of metastatic squamous-cell carcinoma of the uterine cervix using the polymerase chain reaction

Routinely processed fine-needle aspirations of metastatic squamous-cell carcinoma (SCC) were analyzed for human papillomavirus type 16 (HPV-16) using the polymerase chain reaction (PCR), an in vitro DNA amplification method. HPV-16 DNA was detected in five of seven (71%) metastases from SCC of the uterine cervix. In two cases in which the primary tumor was available for comparison, the HPV-16 DNA content of the primary tumor and of the metastasis was identical. HPV-16 was not found in a metastatic SCC from the lung or in a metastatic nasopharyngeal SCC. These findings demonstrate that HPV-16 DNA sequences can be readily detected in routinely processed fine-needle aspirations using the polymerase chain reaction. The finding of HPV-16 DNA in a metastasis may serve to direct a search for a primary site of origin.     

Correlation of histologic types of carcinoma of the uterine cervix and human papillomavirus and herpes simplex virus type 2 DNA sequences in the uterine cervical biopsies

Summary Forty patients with invasive cancer of cervix from New Delhi were examined for the presence of human papillomavirus (HPV) and herpes simplex virus (HSV) type 2 DNA sequences in a Southern hybridization assay. Data were analysed according to the histologic type of cancer. HPV DNA sequences were detected in 82.5% biopsies and HSV-2 DNA sequences were found in 10% biopsies. HPV-16 DNA sequences were found either alone or together with HPV-18 and/or HSV-2 Bgl II N fragment in 55% biopsies from keratinizing squamous cell carcinoma, whereas HPV-18 sequences were found in 35% biopsies. Similarly, 50% biopsies from patients with non keratinizing squamous cell carcinoma contained HPV-16 DNA and 38.9% biopsies had HPV-18 DNA. HSV-2 Bgl II N DNA sequences were present in 10% biopsies which were also positive for HPV-16 and/or HPV-18 DNA sequences. Two biopsies from adenocarcinoma of uterine cervix contained HPV-18 and HPV-16 DNA sequences. Therefore, no significant correlation seems to exist between HPV-types and histologic types or grades of differentiation of tumor.     

Correlation between E-cadherin and CD44 adhesion molecules expression and cervical lymph node metastasis in oral tongue SCC: Predictive significance or not

The aim of this article was to evaluate the expression of E-cadherin and CD44 adhesion molecule in oral tongue squamous cell carcinoma (SCC) since inappropriate expression of adhesion molecules raises the metastatic ability of the tumor cells.Biopsy specimens from 92 patients with tongue SCC were examined for the expression of E-cadherin and CD44 by immunohistochemistry. The relationship of immunoreactivity with tumor stage and cervical lymph node metastasis was then analyzed.Sixty-one patients (66.3%) had reduced or negative staining for CD44. Weak or absent staining for E-cadherin was seen in 14 patients (15.21%). Cervical lymph node metastasis is associated with decreased or negative staining for CD44, but no association was found between E-cadherin immunoreactivity and nodal metastasis.Our study reveals that reduced expression of CD44 could be an indicator of high invasiveness of tumor by increasing cervical lymph node metastasis.     

Relationship between human papillomavirus infection and overexpression of p53 protein in cervical carcinomas and lymph node metastases

Overexpression of p53 protein is common in cervical carcinoma. We investigated archival biopsies from 26 cervical cancer patients (24 with available lymph nodes) to determine the relationship between p53 overexpression and HPV infection at the cervix and lymph nodes. Twelve cervical carcinoma patients had p53 protein in cervical biopsies detectable by immunohistochemistry using monoclonal antibody DO-1, and 22 were positive for HPV DNA in polymerase chain reaction assays (16 contained HPV-16; 3, HPV-18; and, 3 HPV-X). Seven cervical cancer patients had one or more lymph nodes positive for p53 protein, and all but one of these were concordantly p53 positive at the cervix. However, detection of p53 protein in cervical biopsies was predictive neither of the expression of p53 at draining lymph nodes (P > 0.1) nor of the occurrence of metastases (P > 0.1). Fourteen patients were positive at one or more lymph nodes for HPV DNA. Cervical positivity for HPV DNA was associated significantly with concordant HPV positivity at the lymph nodes (P = 0.039) and was predictive of metastases (P = 0.019). There was no association between positivity for p53 and for HPV DNA at primary cervical carcinomas or at the lymph nodes (all P > 0.1). We conclude that, although detectable p53 protein is a common feature of cervical carcinomas, it is not predictive of metastases and is independent of HPV infection. J. Med. Virol. 53:111–117, 1997. © 1997 Wiley-Liss, Inc.     

High prevalence of intermediate-risk human papillomavirus infection in uterine cervices of Kenyan women infected with human immunodeficiency virus

The aim of this study was to investigate an association between certain human papillomavirus (HPV) types and human immunodeficiency virus (HIV) infections. Sexually active females (n = 487; 19-61 years old) were enrolled in the study. Subjects underwent Pap testing and evaluations of HIV and HPV infection status on uterine cervical cell samples. HPV genotyping was performed using a Kurabo GeneSQUARE DNA microarray test. Overall, 23 HPV genotypes were detected, and the most prevalent HPV genotype was HPV-52, followed by HPV-39, -54, -45, -56, -53, -31, -42, -16, -68, and -51. HPV-30, -53, -54, -61, and -66, which are associated with abnormal cytology, are categorized as intermediate-risk in this study. Detection of both high- and intermediate-risk HPV types was significantly associated with cervical abnormality and HIV infection. Multivariate analysis revealed that some high-risk HPV types (HPV-31, -45, -51, -56, and -59) and most intermediate-risk HPV types were associated with HIV infection, while the high-risk types (HPV-16, -18, -33, -35, -39, -52, -58, and -68) were not. The oncogenic effect of the most malignant HPV types (e.g., HPV-16 and -18) appear to be lower, while that of intermediate-risk types are greater, in areas with a high prevalence of HIV infection.     

Types of Human Papillomavirus Observed in Hospital-Based Population

Background and Objectives: Human papillomavirus (HPV) is the causative agent of cervical cancer, a major cause of cancer mortality in Indian women. The current study was undertaken to add information to the existing data on HPV type distribution in Indians, in an attempt to document HPV types for future vaccination programme, if any. Materials and Methods: HPV infection was screened in 223 cervical cancer cases and 2408 healthy women without cancer and cervical intraepithelial neoplasia (control). HPV was typed using polymerase chain reaction, Southern hybridisation using specific probes and HPV GenoArray (Hybribio) test. Results: HPV DNA was found in 92.8% of cases and 7.3% of controls. Of the 383 HPV-infected women, 30.0% had single infection; 50.9% had multiple infections (two or more types) and 19.1% were infected with HPV types other than HPV-16, -18, -6 and -11. Besides HPV-16, HPV-51 and HPV-33 were also seen as single infection in cases. In cases, HPV-18 or its homologous HPV-45 was always present as co-infection with HPV-16 or with other high-risk type. Binary logistic regression (backward) analysis highlighted significant association of age, parity and socioeconomic status with HPV infection. The present study highlighted the presence of multiple HPV infection (186 of 207, 89.9%) along with HPV-16 in women with cervical cancer. In control, 27.3% were co-infected with other sexually transmitted infections, while Chlamydia trachomatis infection was seen in 13% of cases. Conclusions: The study highlighted the type of HPV infection seen among the hospital-based population. For better screening, HPV tests available in the market should include all the types seen in the population.     

Distribution of HPV genotypes in uterine cervical lesions in Yanbian, northern China

The aim of the present study was to investigate the distribution of HPV genotypes in uterine cervical lesions in Yanbian, northern China. HPV-DNA chip (oligonucleotide microarray) and cervical biopsy were used for 322 women in 1998-2005. All the normal cervical epithelia were negative for HPV. The positive rate of high-risk HPV was 33.9% in cervical intra-epithelial neoplasia (CIN)-1, 51.6% in CIN-2, 57.7% in CIN-3, 66.7% in cervical glandular intra-epithelial neoplasia (CGIN), 91.7% in squamous cell carcinoma (SCC), and 78.6% in adenocarcinoma. HPV-16 was the major type in all CIN and SCC cervical lesions, but in cervical adenocarcinoma HPV-18 was the most common type, and HPV-16 was the second most common type. Several cases of CIN-3, SCC and adenocarcinoma had multiple types of HPV, but there was none in CIN-1/2. In summary, HPV-16 is the type most frequently involved in the development of SCC of the cervix, and this may be helpful for the prediction of the development and progress of CIN-2/3, whereas both HPV-18 and -16 play a prominent role in the development of adenocarcinoma and CGIN of the cervix in Yanbian, northern China.     

Routine genotyping of human papillomavirus samples in Denmark

In order to examine a sensitive unbiased consensus PCR with routine sequencing for HPV typing, we analysed Danish male and female patients suspected of having an HPV infection. We used the well-characterised nested PCR setting with MY09/MY11 and GP5+/GP6+ primers, followed by routine cycle sequencing. Of 1283 clinical samples from female patients based on suspected HPV infection, we found 379 (29%) negatives and 894 (70%) positives. Samples containing >5000 HPV copies/ml were genotyped by sequencing. Of the 552 HPV genotyped samples from women >15 years of age, 398 were characterised as high-risk types and the remaining 154 as low-risk types. The most commonly found high-risk types were HPV-16, HPV-31, HPV-33, HPV-18, HPV-58, and HPV-52, and the most commonly found low-risk types were HPV-6, HPV-53 and HPV-11. In addition, we observed that other typing assays could not perform as sensitively or accurately as the nested PCR/cycle sequencing method used in this study. For instance, 87 out of 552 genotyped samples could not have been typed correctly in the Hybrid Capture II assay. Of these 87 samples, 46 (53%) were considered as high-risk types.     

Prevalence of high-risk human papillomavirus in primary squamous cell carcinoma of urinary bladder

Studies have demonstrated an etiologic role of high-risk human papillomavirus (HR-HPV) infection for epithelial malignancies, including most cervical carcinomas, anogenital cancers, and carcinomas of the head and neck; however, a causative role of HPV infection for bladder cancer is controversial. The purpose of this study was to investigate the prevalence of HR-HPV in primary bladder carcinoma to determine the association between HPV infection and the squamous cell component of urothelial carcinoma of the bladder. Furthermore, we evaluated the utility of p16 overexpression as a surrogate marker for HPV infection in these cancers and the correlation of this with tumor stage. Our study included 33 cases of squamous cell carcinoma (SCC) of the urinary bladder. Tumors deemed primary from the bladder were selected and either showed predominant (>50 %) or pure squamous differentiation. Immunohistochemical study for p16 and HR-HPV by RNA in situ hybridization (ISH) was performed in all cases. p16 expression was detected in 7 cases (28 %, 7/25) of urothelial carcinoma with squamous differentiation and not detected in any of the 8 cases (0%, 0/8) of pure SCC. Detection of HR-HPV by ISH was negative in all 33 cases (0%, 0/33). There was no association between p16 overexpression and the presence of HPV infection in squamous cell carcinomas of the bladder. p16 should not be used as a surrogate marker for evidence of HPV infection. Our study suggests that HPV infection does not play an etiologic role in the development of bladder cancer and should not be used as a diagnostic adjunct for these cases.     

HPV genotype prevalence in cytologically abnormal cervical samples from women living in south Italy

Human papillomavirus (HPV) infection is the commonest sexually transmitted infection, and high-risk HPV types are associated with cervical carcinogenesis. This study investigated: the HPV type-specific prevalence in 970 women with an abnormal cytological diagnosis; and the association of HPV infection and cervical disease in a subset of 626 women with a histological diagnosis. HPV-DNA was researched by nested PCR/sequencing and the INNOLiPA HPV Genotyping assay. The data were analysed by the chi-square test (p相似文献   

Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck

BACKGROUND: Oncogenic human papillomaviruses (HPVs), especially HPV type 16 (HPV-16), cause anogenital epithelial cancers and are suspected of causing epithelial cancers of the head and neck. METHODS: To examine the relation between head and neck cancers and HPVs, we performed a nested case-control study within a joint Nordic cohort in which serum samples were collected from almost 900,000 subjects. Samples collected at enrollment from 292 persons in whom squamous-cell carcinoma of the head and neck developed, on average, 9.4 years after enrollment and from 1568 matched controls were analyzed for antibodies against HPV-16, HPV-18, HPV-33, and HPV-73 and for cotinine levels as a marker of smoking habits. Polymerase-chain-reaction (PCR) analyses for HPV DNA were performed in tumor tissue from 160 of the study patients with cancer. RESULTS: After adjustment for cotinine levels, the odds ratio for squamous-cell carcinoma of the head and neck in subjects who were seropositive for HPV-16 was 2.2 (95 percent confidence interval, 1.4 to 3.4). No increased risk was observed for other HPV types. Fifty percent of oropharyngeal and 14 percent of tongue cancers contained HPV-16 DNA, according to PCR analysis. CONCLUSIONS: HPV-16 infection may be a risk factor for squamous-cell carcinoma of the head and neck.     

Human papillomavirus infection and the malignant transformation of sinonasal inverted papilloma: A meta-analysis

A growing number of molecular epidemiological studies have been conducted to evaluate the association between human papillomavirus (HPV) infection and the malignancy of sinonasal inverted papilloma (SNIP). However, the results remain inconclusive. Here, a meta-analysis was conducted to quantitatively assess this association. Case-control studies investigating SNIP tissues for presence of HPV DNA were identified. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Mantel-Haenszel method. An assessment of publication bias and sensitivity analysis were also performed. We calculated a pooled OR of 2.16 (95% CI = 1.46–3.21, P < 0.001) without statistically significant heterogeneity or publication bias. Stratification by HPV type showed a stronger association for patients with high-risk HPV (hrHPV) types, HPV-16, HPV-18, and HPV-16/18 infection (OR = 8.8 [95% CI: 4.73–16.38], 8.04 [95% CI: 3.34–19.39], 18.57 [95% CI: 4.56–75.70], and 26.24 [4.35–158.47], respectively). When only using PCR studies, pooled ORs for patients with hrHPV, HPV-16, and HPV18 infection still reached statistical significance. However, Egger’s test reflected significant publication bias in the HPV-16 sub-analysis (P = 0.06), and the adjusted OR was no longer statistically significant (OR = 1.65, 95%CI: 0.58–4.63). These results suggest that HPV infection, especially hrHPV (HPV-18), is significantly associated with malignant SNIP.     

Study of multiple human papillomavirus-related lesions of the lower female genital tract by in situ hybridization

Twenty-six women with multiple human papillomavirus (HPV)-related lesions of the lower genital tract were investigated by immunohistochemistry for the internal genus-specific capsid antigen of HPV and by DNA-DNA in situ hybridization with 35S-radiolabeled probes for sequences of HPV-6/11, HPV-16, and HPV-18. The vulva was the most frequently affected site in all of these cases; the cervix was the second most frequently affected site. The lesions displayed the features of papillomavirus infection in 14 patients, and there was also histologic evidence of early neoplasia in 12 patients. The mean age of patients with and without neoplasia was 40 and 30 years, respectively. Evidence of HPV association was found in 73% of the vulvar lesions and in 40% of the other synchronous lesions by one or both methods. Viral DNA was found in 67% of patients with neoplasia and in 71% of patients without neoplasia. Eleven of 12 HPV-positive patients with neoplasia revealed the presence of HPV-16 in their tissues by in situ hybridization. On the other hand, 50% of those without neoplasia had HPV-16 DNA, whereas the presence of HPV-6/11 was found in the other 50%. The clinical course of the disease, the distribution of HPV type, and the type of antigen in patients with and without neoplasia suggest that progression to neoplasia was associated with HPV-16. These results stress the practical value of the in situ hybridization method for the identification of those patients with HPV infection who are at risk for progression to malignancy.     

Human papillomavirus genotypes and their association with cervical neoplasia in a cohort of Western Australian women

Human papillomavirus (HPV) is known to be the cause of almost all cervical cancers. The genotypes have been classified into high and low risk types according to their oncogenic potential. However, data for many of the genotypes are limited and some (HPV-26, 53, and 66) have no agreed status. A study was undertaken to determine the HPV genotype distribution in women of Western Australia and the association with cervical neoplasia. Liquid based cervical samples from a cohort of 282 Western Australian women were tested for HPV DNA by PCR followed by DNA sequencing to determine HPV genotypes. HPV-53 and HPV-16 were the most common genotypes found in this population. In addition 86 archived liquid based cervical samples from women with cervical intraepithelial neoplasia grades 1-3 (CIN 1-3) were tested for HPV DNA. Also 32 archived paraffin biopsy samples from women with squamous cell carcinoma were also tested. HPV-16 was the most common genotype found in these samples. Of the cohort of Western Australian women tested, 27% were found to contain HPV and approximately half of these contained known high-risk HPV genotypes, but only 30% of these were types 16 or 18. The data from this study indicate that HPV-53 is not oncogenic based on an R value and odds ratio (OR) of zero. The data also suggest that HPV-73 may be oncogenic, while HPV-66 is unlikely to be. Two high-risk HPV genotypes that are associated with the Asian region (HPV-52 and HPV-58) were found in Western Australian women suggesting a possible epidemiological link between women in these countries.     

Cervical mucus antibodies against human papillomavirus type 16, 18, and 33 capsids in relation to presence of viral DNA.

To investigate whether cervical mucus antibodies against human papillomavirus (HPV) capsids are associated with the detection of HPV DNA or HPV-related cytological diagnoses, 611 samples of cervical secretions from 359 women referred to a colposcopy clinic were tested by an enzyme-linked immunosorbent assay for the presence of immunoglobulin A (IgA) antibodies against HPV capsids of HPV type 16, 18, or 33 and for the presence of cervical HPV DNA by PCR. Among subjects with at least one cervical sample positive for HPV type 16 (HPV-16) DNA, 28.1% also had at least one HPV-16 IgA-positive cervical sample (odds ratio [OR] = 2.9; P = 0.0003). IgA to HPV-18 was also more common among HPV-18 DNA-positive subjects (OR = 3.1; P = 0.0325) and IgA to HPV-33 was more common among HPV-33 DNA-positive subjects (OR = 4.2; P = 0.0023). Cervical IgA antibodies to HPV-16 were also more common among patients with cervical intraepithelial neoplasia, particularly among patients with cervical intraepithelial neoplasia grade I (P < 0.0005). The data indicate that an HPV type-restricted IgA antibody response against HPV capsids is detectable in cervical mucus and is associated with a concomitant cervical HPV infection.