Occurrences of human papilloma virus DNA in cervical carcinomas

Out of 16 cases involving a cervical carcinoma that were investigated by Southern blot hybridization, found were human papilloma virus (HPV) types 16 and 18 DNA sequences in 8 (50%) and in one (6.3%), respectively. Six out of the 8 HPV 16-positive specimens were from squamous cell carcinomas, one was from an adenocarcinoma, and the remaining specimen was from an argyrophil small cell carcinoma. In 7 out of 9 HPV-positive specimens, the viral sequences were integrated in the tumor cell genome, whereas in the remaining two they were not integrated and remained circular and/or oligomeric in form.     

The physical state of human papillomavirus type 16 DNA in cervical carcinomas of Hong Kong Chinese.

The presence of human papillomavirus (HPV) in 15 cervical carcinoma specimens obtained from Hong Kong Chinese patients was analyzed by Southern blot hybridization studies. In nine (60%) of them, HPV 16 genomes were detected, while two others (13.3%) were found to harbor HPV DNA of unknown type closely related to HPV 16. All of them were classified as squamous cell carcinomas according to WHO guidelines. In addition, the presence of HPV 18 was shown in another two (13.3%) squamous cell carcinoma samples. Among the nine tumors harboring HPV 16, four specimens (44.4%) have HPV in integrated forms, while four others (44.4%) have HPV in episomal forms. The simultaneous presence of both episomal and integrated forms was demonstrated in the remaining tissue sample (11.2%). The result obtained here indicates a strong association between HPV infection and cervical carcinogenesis in Hong Kong Chinese, with HPV 16 prevalent in squamous cell carcinoma. Moreover, the persistence of HPV 16 episomes in some of the tumor specimens suggests that extrachromosomal HPV DNA, possibly acting synergistically with other oncogenic factors, is also capable of inducing cervical cancer.     

Human papillomavirus detected in female breast carcinomas in Japan

To investigate the aetiological role of human papillomavirus (HPV) in breast cancer, we examined the presence, genotype, viral load, and physical status of HPV in 124 Japanese female patients with breast carcinoma. Human papillomavirus presence was examined by PCR using SPF10 primers, and primer sets targeting the E6 region of HPV-16, -18, and -33. The INNO-LiPA HPV genotyping kit was used to determine genotype. Human papillomavirus DNA was detected in 26 (21%) breast carcinomas. The most frequently detected HPV genotype was HPV-16 (92%), followed by HPV-6 (46%), HPV-18 (12%), and HPV-33 (4%). In 11 normal epithelium specimens adjacent to 11 HPV-16-positive carcinomas, 7 were HPV-16-positive. However, none of the normal breast tissue specimens adjacent to HPV-negative breast carcinomas were HPV-positive. The real-time PCR analysis suggested the presence of integrated form of viral DNA in all HPV-16-positive samples, and estimated viral load was low with a geometric mean of 5.4 copies per 10(4) cells. In conclusion, although HPV DNA was detected in 26 (21%) breast carcinomas and, in all HPV-16-positive cases, the HPV genome was considered integrated into the host genome, their low viral loads suggest it is unlikely that integrated HPV is aetiologically involved in the development of Japanese breast carcinomas that we examined.     

Human papillomavirus-16 is integrated in lung carcinomas: a study in Chile

The human papillomavirus (HPV) was detected in 20 (29%) out of 69 lung carcinomas (LCs) in Chile, by PCR and Southern blot, and was more frequently detected in squamous cell carcinoma (SQC) than in adenocarcinomas (46 vs 9%, P=0.001). HPV-16, positive in 11 cases, was the most frequently detected HPV genotype determined by DNA sequencing. HPV-16 E2/E6 ratio, estimated from real-time PCR analysis, was much lower than the unity, suggesting that at least a partial HPV-16 genome was integrated in all but one HPV-16-positive SQCs. The remaining one case was suspected to have only episomal HPV-16. Although the viral load was low in most of the LCs, a case showed the HPV-16 copy number as high as 8479 per nanogram DNA, which was even a few times higher than the minimum viral load of seven cervical carcinomas (observed viral load: 3356-609 392 per nanogram DNA). The expression of the HPV-16/18 E6 protein was found in only two HPV-16-positive SQCs (13%) but not in the case with the highest viral load. Although the viral load was in general very low and HPV E6 expression is none or weak, further studies seem warranted to examine aetiological involvement of high-risk HPV in lung carcinogenesis.     

Reactivity to human papillomavirus type 16 L1 virus-like particles in sera from patients with genital cancer and patients with carcinomas at five different extragenital sites

A retrospective seroepidemiologic study was performed to examine the association between human papillomaviruses (HPV) 16 infection and carcinomas of the oropharynx, the oesophagus, penis and vagina. Sera were selected from the serum bank from the Antoni van Leeuwenhoek Hospital (Netherlands Cancer Institute) and the Slotervaart Hospital in Amsterdam, the Netherlands. Presence of HPV 16 specific antibody was assessed using HPV 16 L1 capsids. Sera positive for HPV 16 capsid antibody were further tested for antibody against HPV 16 E7 peptides. Prevalence of antibody against HPV 16 L1 capsids among both the negative control group without cancer and the negative control group with gastric cancer was 18%, while seroprevalence among the control group of patients with HPV-associated cervical squamous cell carcinoma was 47% (P<0.001). Among the patients with penile squamous cell carcinoma seroprevalence was 38% (P<0.001), among patients with oropharyngeal carcinoma 33% (P=0.04) and among patients with oesophageal squamous cell carcinoma 14% (P=0.7). The serological evidence for association between HPV 16 infection and both oropharyngeal carcinoma and penile carcinoma was established. The conclusion that no association was found between the presence of antibody against HPV 16 L1 capsids and oesophageal squamous cell carcinoma was in accordance with results of other studies carried out in the Netherlands using HPV DNA technology. In the subjects with HPV 16 L1 capsid antibody, no association was found between the antibody against HPV 16 E7 and clinical outcome.     

HPV Positive Bronchopulmonary Carcinomas in Women with Previous High-grade Cervical Intraepithelial Neoplasia (CIN III)

A significant higher incidence of some cancers, especially lung cancer, has been found in women with previous HPV-related (human papillomavirus) urogenital and anal neoplasias than in individuals without this particular clinical history. The aim of our study was to investigate whether HPV is present in both CIN III (cervical intraepithelial neoplasia) lesions and bronchopulmonary second primary cancers in women with a clinical history of both diseases. Paraffin-embedded tumour tissue from 75 patients with bronchopulmonary carcinomas was examined using the polymerase chain reaction (PCR) technique and in situ hybridization for the presence of human HPV. In total, 51 primary tumours without metastases, 11 primary tumours with metastases and 13 lymph node metastases without available tissue from primary tumours were analysed. In our study 37/75 primary bronchopulmonary tumours (49%) were identified as HPV positive by the PCR method: 18 cases were purely HPV 16 positive (49%), 12 were purely HPV 6 positive (32%), 5 cases were HPV 16/6 positive (14%), 1 case was HPV 16/11 positive (2%) and 1 case was HPV 16/18 positive (2%). Fourteen metastases were HPV positive, and HPV 16, 11 and 6 were detected in both regional and distant metastases. Two of the HPV 16-positive metastases were brain metastases from two separate HPV 16-positive primary tumours; 35% of the HPV-positive cases were adenocarcinomas, 30% squamous cell carcinomas, 22% oat cell carcinomas, 5% large cell carcinomas, 3% anaplastic carcinoma, 3% low-differentiated carcinoma, and 3% malignant cylindroma. The CIN III lesions from 34 of the 37 HPV-positive bronchopulmonary carcinomas were analysed by PCR. The overall HPV positivity in the CIN III lesions was 74% (25/34 cases): 48% were purely HPV 16 positive, 24% purely HPV 6 positive, 24% HPV 16/6 positive and 4% were HPV 18 positive. Our results indicate that HPV is also involved in the development of bronchopulmonary cancers in women with a history of CIN III lesions.     

Human papillomavirus in lung carcinomas among three Latin American countries

The presence of human papillomavirus (HPV) genome in lung carcinomas has been reported worldwide but its frequency varies from country to country. We examined HPV genome in 36 lung carcinomas, consisting of 14 squamous cell carcinomas, 13 adenocarcinomas, and 9 small cell carcinomas, collected from Colombia, Mexico and Peru. PCR analysis using GP5+/GP6+ primers, combined with Southern blot hybridization, found the presence of HPV genome in 10 (28%) of 36 cases. This percentage is similar to the value of 22% reported by Syrj?nen, who conducted a meta-analysis of nearly 2500 lung carcinomas examined to date. Genotype analysis revealed that the most predominant genotype was HPV-16 (7 cases), followed by HPV-18 (2 cases) and HPV-33 (1 case). HPV-16 was more frequently found among female than male cases (P=0.008) but was not detected in any adenocarcinoma cases. On the other hand, HPV-18 and HPV-33 were detected only among male cases. These HPV genotypes were detected only in adenocarcinomas, and all the HPV genotypes detected in this histological type were HPV-18 or HPV-33. The frequency of HPV-16 positive cases among all the HPV positive cases differed in the sexes (P=0.033) and differed in the three histological types (P=0.017). The presence of HPV tended to be more frequent in well-differentiated tumors when squamous cell carcinomas and adenocarcinomas were combined. However, it was not statistically significant (P=0.093). Neither p16 nor p53 expression in carcinoma cells was related to the proportion of HPV-positive cases. In conclusion, high-risk HPV DNA was detected in 28% of lung carcinomas. The predisposition of HPV-16 to female cases and to non-adenomatous carcinomas warrants further investigation.     

HPV types and cofactors causing cervical cancer in Peru

We conducted a hospital-based case-control study in Peru of 198 women with histologically confirmed cervical cancer (173 squamous cell carcinomas and 25 cases of adenocarcinoma/adenosquamous carcinoma) and 196 control women. Information on risk factors was obtained by personal interview. Using PCR-based assays on exfoliated cervical cells and biopsy specimens, HPV DNA was detected in 95.3% of women with squamous cell carcinoma and in 92.0% of women with adenocarcinoma/adenosquamous carcinoma compared with 17.7% in control women. The age-adjusted odds ratio was 116.0 (95% Cl = 48.6-276.0) for squamous cell carcinoma and 51.4 (95% Cl = 11.4-232.0) for adenocarcinoma/adenosquamous carcinoma. The commonest types in women with cervical cancer were HPV 16, 18, 31, 52 and 35. The association with the various HPV types was equally strong for the two most common types (HPV 16 and 18) as for the other less common types. In addition to HPV, long-term use of oral contraceptives and smoking were associated with an increased risk. HPV is the main cause of both squamous cell carcinoma and adenocarcinoma in Peruvian women.     

Detection and genotype analysis of human papillomavirus in non-small cell lung cancer patients

Although the role of human papillomavirus (HPV) in the development of uterine cervical cancer is well established, the role of HPV in lung carcinogenesis remains controversial. The detection rates of HPV DNA are subject to a wide variation from 0 to 100 %. This is partly influenced by the detection techniques employed. To elucidate the impact of HPV infection on lung parenchyma, we analyzed 100 non-small cell lung cancer (NSCLC) specimens (39 squamous cell carcinomas, 50 adenocarcinomas, 5 samples with characteristics of both squamous cell and adenocarcinoma, 5 undifferentiated and 1 large cell carcinoma) from the region of Crete, Greece. Sixteen non-cancerous samples served as the negative controls. DNA was extracted from 100 paraffin-embedded tissue sections obtained from NSCLC patients. The specimens were examined for the detection of HPV DNA by Real-Time PCR using GP5+/GP6+ primers. Furthermore, the HPV-positive samples were subjected to genotyping. In contrast to the absence of viral genomes in the control samples, HPV DNA was detected in 19 NSCLC specimens (19 %). In particular, 4 squamous cell carcinomas, 12 adenocarcinomas, 1 sample with characteristics of both squamous cell and adenocarcinoma, and 2 undifferentiated samples were HPV-positive. The distribution of HPV genotypes was as follows: HPV 16: eight cases (42.1 %); HPV 11: three cases (15.8 %); HPV 6: one case (5.2 %); HPV 59: one case (5.2 %); HPV 33: two cases (10.5 %); HPV 31: two cases (10.5 %) and HPV 18: two cases (10.5 %). The presence of HPV in the tumor samples provides evidence of the potential role of HPV in NSCLC and strongly argues for additional research on this issue.     

Oncogenic association of specific human papillomavirus types with cervical neoplasia

Molecular hybridization analysis of human papillomavirus (HPV) DNA from 190 cervical biopsy specimens from women in the United States, Brazil, and Peru revealed viral sequences in 2 (9%) of 23 biopsy specimens of normal mature squamous epithelium, 7 (44%) of 16 biopsy specimens of metaplastic squamous epithelia, 60 (77%) of 78 cervical intraepithelial neoplasia (CIN), 57 (89%) of 64 invasive squamous carcinomas, and 8 (89%) of 9 endocervical adenocarcinomas. HPV typing by DNA hybridization revealed HPV 6 and HPV 11 sequences in metaplastic squamous epithelia, CIN I, and CIN II, but not in CIN III lesions or invasive carcinomas. HPV 16 was detected in metaplastic epithelium and in nearly half of the invasive squamous carcinomas and adenocarcinomas. It was present in 31% of CIN lesions, increasing in frequency with the severity of CIN from 20% of CIN I to 50% of CIN III. HPV 16 showed a striking difference in geographic distribution, being detected in 36% of the carcinomas from the United States compared to 64% of the carcinomas from Brazil and Peru. HPV 18 was found in metaplastic epithelia and in 17% of carcinomas but in only 1% of CIN lesions. HPV 31 was not found in metaplastic epithelium but was present in 6% of carcinomas and in 18% of CIN lesions. In addition, a group of uncharacterized HPVs, not corresponding to any of the probes used, was found in 5% of normal and metaplastic epithelia and in 18% of CIN and 19% of invasive cancers. These results suggest that individual HPV types that infect the cervix have varying degrees of oncogenic association. HPV 6 and HPV 11 appear to have very little oncogenic association, HPV 31 has low oncogenic association, and HPV 16 and HPV 18 have high oncogenic association.     

Frequent detection of human papilloma viruses in cervical dysplasia by PCR single-strand DNA-conformational polymorphism analysis

BACKGROUND: To clarify the pathogenicity of multiple human papilloma virus (HPV) infection, we applied SSCP (single-strand DNA conformation polymorphism) analysis for cervical neoplastic lesions. MATERIALS AND METHODS: Two hundred and sixty-six cervical swab specimens from normal cervix (n=64), cervical dysplasia (n=95), carcinoma in situ (n=79) and cervical cancer (n=28), were studied by nested PCR-SSCP analysis using L1 consensus primers. RESULTS: In 95 samples of cervical dysplasia, HPV infection was detected in 98.9% (94 out of 95), multiple HPV infection was detected in 38.3% (36 out of 94). In 19 squamous cell carcinomas (SCC) and 9 adenocarcinomas, the detection rate of HPV infection was 84.2% (16 out of 19) and 55.6% (5 out of 9), respectively, and all HPV-positive cases showed infection of a single HPV, among which HPV 16 occupied 68.6% (11 out of 16) in SCC and HPV 18 occupied 100% (5 out of 5) in adenocarcinoma. CONCLUSION: Multiple HPV infections may be concerned with pathogenicity in cervical dysplasia; however, the single infection with only a few HPV types, such as type 16 in SCC and type 18 in adenocarcinoma, may play a role in cervical carcinogenesis.     

Occurrence of human papillomavirus DNA in primary lung neoplasms.

The occurrence of human papillomavirus (HPV) DNA in primary lung carcinomas and in squamous metaplasia of the bronchus was studied using in situ hybridization techniques and commercially available biotinylated DNA probes to HPV subtypes 6/11, 16/18, and 31/33/35. The authors found HPV DNA in six of 20 cases of squamous cell carcinoma and one of six cases of large cell undifferentiated carcinoma. There were two cases each of the 6/11 serotypes and the 16/18 serotypes and three cases of the 31/33/35 serotypes. Infected cells of the squamous carcinomas uniformly showed koilocytosis. No case of adenocarcinoma, bronchioloalveolar carcinoma, or small cell carcinoma was positive (of 32 cases). Areas of squamous metaplasia in infected tumors showed similar HPV DNA expression in 15% of cases, especially in those with condylomatous atypia. In 5.8% of random bronchial biopsies of squamous metaplasia, HPV DNA was identified. The relationship of HPV infection to the development of upper and lower respiratory tract carcinomas is discussed.     

Genome amplification of human papillomavirus types 16 and 18 in cervical carcinomas is related to the retention of E1/E2 genes

The level of amplification (copy number/cell) of HPV16 and HPV18 viral genomes and its correlation with the presence of E1/E2 genes were analyzed in a sample of 42 HPV16-and 21 HPV18-positive cervical carcinomas of different clinical stages and histological types. The viral copy number/cell was assessed by dot-blot hybridization and the presence of E1/E2 genes by PCR and Southern blot. The copy number/cell was significantly lower in HPV18-positive than in HPV16-postive tumours (23 ? 8 and 457 ? 191 respectively). Nearly half of the HPV16s (43%) were distributed similarly to the HPV18s in the ranges of 50 or less copies, having its peak at the group of 1 to 10 copies, whereas the remaining HPV16s (57%) spread over the groups of 51 or more copies, with another peak at the group of 101 to 500. The E1/E2 region was absent in all tumours positive for HPV18 and present in 64% of those positive for HPV16. The HPV16 tumours negative for E1 /E2 had a much lower viral copy number (17 ? 12) than the positive ones (582 ? 212), thus resembling HPV18-positive tumours. Viral copy number was negatively correlated with the clinical stage of the tumours and directly associated with the degree of histological differentiation. However, these correlations are primarily attributable to the presence or absence of an intact E1/E2 region.     

Human papillomavirus types and localization in adenocarcinoma and adenosquamous carcinoma of the uterine cervix: a study by in situ DNA hybridization

Formalin-fixed, paraffin-embedded tissues from 108 cases of invasive carcinoma of the uterine cervix, consisting of 40 cases of adenocarcinoma, 44 cases of adenosquamous carcinoma, and, as a control, 24 cases of squamous cell carcinoma were examined for the presence of human papillomavirus (HPV) DNA by in situ hybridization of high sensitivity using tritium-labeled HPV-2, HPV-6, HPV-16, and HPV-18 DNA probes. This method detects five genome copies of homologous HPV DNA per cell. HPV DNA was detected with mixed HPV DNA probes in 17 cases (42.5%) of adenocarcinoma, 16 cases (36.4%) of adenosquamous carcinoma, and in 13 cases (54.2%) of squamous cell carcinoma. The types of HPV DNA in the HPV-positive tissues were also analyzed with each individual probe under high stringency conditions. HPV-18 DNA was detected in all but one case of the HPV DNA-positive adenocarcinoma and one-half of the HPV DNA-positive adenosquamous carcinoma. HPV-16 DNA was detected in one case of the HPV DNA-positive adenocarcinoma, one-half of the HPV DNA-positive adenosquamous carcinoma, and all cases of the HPV DNA-positive squamous cell carcinoma. HPV DNA was confined to the areas of carcinoma and squamous cervical intraepithelial neoplasia (CIN) associated with carcinoma. Among 36 cases in which CIN was associated with adenocarcinoma (9 cases), adenosquamous carcinoma (19 cases), and squamous cell carcinoma (8 cases), the same type of HPV DNA was present in the carcinoma and the associated CIN that constituted 12 cases (3 adenocarcinoma, 5 adenosquamous carcinoma, and 4 squamous cell carcinoma). Two cases (one adenocarcinoma and one adenosquamous carcinoma) contained HPV DNA in the carcinoma but not in the associated CIN. The incidence of HPV DNA did not show a significant correlation with the existence of CIN or histological differentiation of carcinoma.     

Differences in human papillomavirus type distribution in high‐grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe

Knowledge of differences in human papillomavirus (HPV)‐type prevalence between high‐grade cervical intraepithelial neoplasia (HG‐CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV‐infected cervical lesions and the potential impact of HPV vaccination on cervical cancer prevention. More than 6,000 women diagnosed with HG‐CIN or ICC from 17 European countries were enrolled in two parallel cross‐sectional studies (108288/108290). Centralised histopathology review and standardised HPV‐DNA typing were applied to formalin‐fixed paraffin‐embedded cervical specimens dated 2001–2008. The pooled prevalence of individual HPV types was estimated using meta‐analytic methods. A total of 3,103 women were diagnosed with HG‐CIN and a total of 3,162 with ICC (median ages: 34 and 49 years, respectively), of which 98.5 and 91.8% were HPV‐positive, respectively. The most common HPV types in women with HG‐CIN were HPV16/33/31 (59.9/10.5/9.0%) and in ICC were HPV16/18/45 (63.3/15.2/5.3%). In squamous cell carcinomas, HPV16/18/33 were most frequent (66.2/10.8/5.3%), and in adenocarcinomas, HPV16/18/45 (54.2/40.4/8.3%). The prevalence of HPV16/18/45 was 1.1/3.5/2.5 times higher in ICC than in HG‐CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/‘other’ (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/‘other’ (15/23/20/17 years). In Europe, HPV16 predominates in both HG‐CIN and ICC, whereas HPV18/45 are associated with a low median age of ICC. HPV18/45 are more frequent in ICC than HG‐CIN and associated with a high median age of HG‐CIN, with a narrow age interval between HG‐CIN and ICC detection. These findings support the need for primary prevention of HPV16/18/45‐related cervical lesions.     

Prevalence of microsatellite instability,inactivation of mismatch repair genes,p53 mutation,and human papillomavirus infection in Korean oral cancer patients

To determine the etiologic factors of human oral cancer, we examined the prevalence of microsatellite instability (MSI), the inactivation of mismatch repair (MMR) genes, p53 mutation, and human papillomavirus (HPV) infection (HPV-16, -18, and -33) in 86 Korean oral cancer specimens, including 76 squamous cell carcinomas and 10 salivary gland tumors. MSI was observed in 3 of the 76 squamous cell carcinomas (4%) and 2 of 10 salivary gland tumors (20%). As MSI is a hallmark of the inactivation of the MMR genes, the genetic status of hMSH2 and hMLH1, and hypermethylation of the hMLH1 promoter region were investigated in oral cancers displaying MSI. Inactivation of the hMLH1 gene by either mutation or hypermethylation was observed 4 of the 5 MSI oral cancers. Mutation of the p53 gene was found in 11 of 76 squamous cell carcinomas (14.5%) but not in the salivary gland tumors. PCR assay revealed the presence of HPV DNA in 11 of the 76 squamous cell carcinomas (14.5%) and 4 of the 10 salivary gland tumors (40%). Type 18 HPV DNA was predominant in 11 of the HPV-infected squamous cell carcinomas (72.7%) and 4 of the HPV-infected salivary gland tumors (50%). Two squamous cell carcinoma tissues were found both to be HPV-infected and to harbor the p53 mutation. Our results suggest: i) that MSI plays a role in the pathogenesis of Korean oral cancers, squamous cell carcinomas (4%) and salivary gland tumors (20%); ii) that genetic alteration or hypermethylation of the hMLH1 gene may be the principal inactivating mechanism in Korean oral cancer with MSI; and iii) that inactivation of the p53 gene by either mutation or HPV infection is frequent in Korean squamous cell carcinomas (26%) and salivary gland tumors (40%).     

Increasing incidence of CD44v7/8 epitope expression during uterine cervical carcinogenesis

Splice variants of the cell surface glycoprotein CD44 (CD44v) have been implicated in the progression of various human tumors. In the present study, we have examined the expression pattern of a CD44v epitope encoded by the adjacent variant exons v7 and v8 during human cervical carcinogenesis. While only 1/11 normal cervical squamous epithelia was positive for this epitope by immunohistochemistry, 4/21 samples of low-grade squamous intra-epithelial lesions (LSIL), 17/35 samples of high-grade squamous intra-epithelial lesions (HSIL), 11/12 samples of the HSIL subgroup of carcinoma in situ and 17/17 cases of invasive cervical carcinoma showed CD44v7/8 epitope expression. In addition to CD44 variant expression, we have analyzed 67 lesions for the presence of HPV16/18-DNA using PCR. Most of the samples expressing the v7/8 epitope were also HPV16-positive (29/32), whereas only 17/35 of the v7/8-negative samples were HPV16-positive. HPV18 DNA was found in only one invasive carcinoma. Our data suggest that high-risk HPV infection may precede CD44v7/8 expression and that the number of samples expressing the CD44v7/8 epitope increases during carcinogenesis and reaches nearly 100% at the carcinoma in situ stage. This CD44 epitope could, therefore, serve as a diagnostic marker of cervical squamous cell carcinomas and as a possible target for CD44v7/8 epitope-directed therapies. © 1996 Wiley-Liss, Inc.     

Human papillomavirus type 18 variants: histopathology and E6/E7 polymorphisms in three countries

In cervical cancer, human papillomavirus type 18 (HPV 18) and HPV 16 are predominantly related to adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs), respectively. Here, we studied whether the geographically distributed HPV intratypic variants are also associated with histologically different tumors. A total of 44 HPV 18-positive and 91 HPV 16-positive cervical carcinomas from Indonesian, Surinamese and Dutch patients were histologically classified using hematoxilin and eosin, periodic acid Schiff plus and Alcian Blue staining. Samples were sequenced and intratypic variants were classified into the known phylogenetic branches. The Asian Amerindian HPV 18 variant was observed in 56% of ADCs compared to 15% of SCCs (p < 0.006). The African HPV 18 variant was exclusively found in SCCs. By sequencing the HPV 18 E6 and E7 open reading frames, we found predicted amino acid changes only in 8 samples. Two amino acid changes were consistent throughout the African branch. In HPV 16-positive tumors, we did not find a specific linkage between intratypic variants and histopathology. We conclude that HPV 18 intratypic variants are differentially associated with adenocarcinoma and squamous cell carcinoma of the cervix. The findings described here stress the biologic significance of intratypic HPV variants and might help explaining differences in the pathogenesis of cervical ADCs and SCCs.     

Human papillomavirus in high- and low-risk areas of oesophageal squamous cell carcinoma in China

To examine the potential roles of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (ESCC) development, we examined the presence of HPV DNA in paraffin-embedded ESCC tissues collected from two areas with different ESCC incidence rates in China, that is, Gansu (n=26) and Shandong (n=33), using PCR with SPF10 primers, or PCR with GP5+/GP6+ primers combined with Southern blot hybridisation. HPV genotype was determined by the INNO-LiPA HPV genotyping kit. HPV DNA was detected in 17 cases (65%) in Gansu, where ESCC incidence is much higher than in Shandong, where HPV was positive in two samples (6%). HPV genotypes 16 and 18 were detected in 79 and 16% of HPV-positive samples, respectively. Real-time PCR analysis suggested the presence of integrated form of HPV DNA in all the HPV-16-positive samples, but its viral load was estimated to be only <1-2 copies cell(-1). We could not detect HPV 16/18 E6 protein expression by immunostaining in any of the HPV-16-positive samples. Neither p16(INK4a) nor p53 expression was related to HPV presence in ESCCs. Further studies seem warranted to examine the possible aetiological roles of HPV in ESCC.     

Frequency of Human Papillomavirus (HPV) 16 and 18 Detection in Paraffin- Embedded Laryngeal Carcinoma Tissue

Background and Objective: Human papilloma virus (HPV) 16 and HPV18 have been detected in head and neck squamous cell carcinomas (HNSCC) and there is evidence that detection of HPVs would have better prognostic value than patients with HNSCC negative for HPVs. Thus, this study was conducted to evaluate frequency of HPV 16 and HPV 18 genotypes in patients with laryngeal carcinoma. Materials and methods: Fifty formalin-fixed, paraffin-embedded (FFPE) tissue blocks of laryngeal cancers were collected. Sections were prepared at 5 μm and DNA was extracted from each sample and subjected to the polymerase chain reaction (PCR) to detect HPV-16/18 DNA s. Results: All samples were squamous cell carcinomas (SCCs). Overall 14/50 (28%) were positive for HPVs, 8 (18%) with HPV-16 and 6 (12%) with HPV-18. Additionally, 2 (4%) mixed infections of HPV 16 and 18 genotypes were observed among these cases. Conclusions: Overall, 28% of HNSCC samples proved positive for HPV16 and HPV18 genotypes, two high-risk HPV types. It is important to further assess whether such viral infection, could be a risk factor in HNSCC progression.