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Sensitivity of in situ hybridization techniques using biotin- and 35S-labeled human papillomavirus (HPV) DNA probes.

In order to evaluate the sensitivity of our modified in situ DNA hybridization technique using biotinylated probes, formalin fixed, paraffin embedded biopsies from 20 cervical lesions known to contain human papillomavirus (HPV) DNA were re-examined by the technique using both 35S-labeled- and biotinylated HPV DNA probes. The probe concentrations as well as the detection limits of biotin probing were screened by spotting known amounts of HPV 16 DNA on nylon filter, and allowed to hybridize with biotinylated HPV 16 DNA probe. By this method, 4 pg of HPV 16 DNA could be detected using a probe concentration of 0.2 micrograms/ml. HPV DNA could be demonstrated in all 20 biopsies with both hybridization techniques. However, signals in subrabasal cells were detected more frequently with biotin- than with 35S-labeled probes. Additional experiments were performed using three cervical cancer cell lines (with known copy numbers of HPV DNA), to assess the detection limits of HPV infections by the in situ hybridization techniques. The CaSki cells (500-600 HPV 16 copies/cell) were unequivocally positive with both labelling systems. HeLa cells (10-50 HPV 18 copies/cell) were positive with the biotin probing in 10/10 smears, as compared to 7/10 smears when 35S-labeled probes were used. Radioactive probing was inferior to biotinylated probing in detecting the signals in SiHa cells (1-2 HPV 16 copies/cell). This is because even weak background signals could mask true positive signals when 35S-labeled probes are used. In contrast, no background is generated with the biotinylated probes, detected with streptavidin-biotinylated alkaline phosphatase complex. In situ hybridization with biotinylated DNA probes is as sensitive as techniques using 35S-labeled probes for detecting HPV infections in routine cervical biopsies or smears.

Biotin↗

Prevalence of human papillomavirus type 18 DNA in adenocarcinoma and adenosquamous carcinoma of the uterine cervix occurring in Japan.

To identify whether the incidence of human papillomavirus (HPV) type 18 DNA in adenocarcinoma and adenosquamous carcinoma is attributable to the histological types or geographical differences, the presence of HPV-16 and HPV-18 DNA in carcinoma of the uterine cervix from Japan were studied by in situ hybridization using tritium labeled HPV DNA probes. HPV-18 DNA was detected in 5 of 11 cases (45%) of adenocarcinoma, one case of adenocarcinoma in situ and 2 of 3 cases of adenosquamous carcinoma. In contrast, HPV-16 DNA was detected in 2 of 11 cases (18%) of adenocarcinoma, and 3 of 7 cases (43%) of squamous cell carcinoma. Compared with our previous results (Tase et al. 1988), the present results imply that the prevalence of HPV-18 DNA in carcinoma of the uterine cervix is attributable rather to the histological differences than to the geographical differences.

Adenocarcinoma↗

Human papillomavirus DNA detection in Papanicolaou-stained cervical smears with a nonradioactive, in situ hybridization assay.

Archived Papanicolaou-stained cervical smears from women with different cervical pathologies were processed for human papillomavirus (HPV) DNA detection and typing with an in situ hybridization (ISH) assay that employed commercial biotinylated HPV DNA probes. Two HPV DNA probes were utilized: one included HPV genotypes 6/11 and the other, 16/18. The method yielded positive results for HPV DNA 6/11 in 5 cases with condylomata acuminata (100%) and in 2 of 47 with flat warty lesions (4.2%), whereas HPV DNA 16/18 was detected in 29/47 of the latter group (61.7%). In cases with cervical intraepithelial III or invasive squamous cell carcinoma the yield was lower: positive results for HPV DNA 16/18 were obtained in only one of the five cases with one or the other cervical pathology (20%). An analysis of the results showed that the sensitivity of the assay correlated with evidence in the Papanicolaou specimens of pathognomonic cell injury from HPV infection. In the presence of such cytologic features, HPV DNA typing was possible in 37/52 cases (65.4%). In view of the modest difficulty and relatively quick execution of the nonradioactive ISH assay, the authors believe that Papanicolaou cervical smears with cytologic changes of HPV infection could be processed by this method in order to acquire information on the HPV type or types involved in the cervical infection.

DNA Probes, HPV↗

[In situ hybridization study on the detection of HPV DNA in adenocarcinoma and adenosquamous carcinoma of the uterine cervix].

Human papillomavirus (HPV) types 16 and 18 have been found closely associated with squamous cell carcinoma and related lesions of the uterine cervix. In order to investigate the relationship between HPV and adenocarcinoma and adenosquamous carcinoma of the uterine cervix, formalin-fixed, paraffinembedded tissues prepared from 38 cases consisting of 30 cases of adenocarcinoma and 8 cases of adenosquamous carcinoma were examined for the presence of HPV DNA by in situ hybridization with digoxigenin labeled HPV 6/11, 16, 18 DNA probes. HPV DNA was localized on the nuclei of the cancer cells in adenocarcinoma and adenosquamous carcinoma. HPV DNA was detected in 13 cases (43.3%) of adenocarcinoma and 4 cases (50.0%) of adenosquamous carcinoma, and HPV type 18 DNA was detected in 13 cases (34.2%) of adenocarcinoma and adenosquamous carcinoma. These findings suggest an association between HPV, especially HPV type 18, and adenocarcinoma and adenosquamous carcinoma of the uterine cervix.

Adenocarcinoma↗

Comparison of four in situ hybridization methods, based on digoxigenin- and biotin-labelled probes, in detecting HPV DNA in male condylomata acuminata.

We have compared the efficacy of digoxigenin- and biotin-labelled probes in detecting HPV DNA by in situ hybridization on paraffin-embedded tissue sections of 57 male condyloma-suspect genital lesions. Each biopsy was hybridized with at least three of the following four methods: digoxigenin-labelled HPV DNA probes (Dig-HPV), biotinylated HPV-DNA probes (Bio-HPV), and two commercial methods (ViraType in situ and PathoGene), both based on biotinylated DNA probes. The hybridization products were visualized with colourigenic enzyme substrates. In most biopsies, the 4 methods gave equal results although cross-hybridization was most often found with the low-stringency ViraType method. Dig-HPV 6/11 probes gave positive results about twice as often as either of the commercial methods. No such difference, however, was found for HPV 16/18 probes. DNA of any type of HPV 6/11, 16/18 or 31/33/35 or 51 was detected in 28/43 (65%) of lesions showing condyloma acuminatum histology but in none of the 14 biopsies with no histological signs of HPV infection. In HPV-positive condylomata with no cellular atypia. HPV 6/11 was detected in 87% (13/15), and HPV 16/18 in 27% (4/15). In biopsies with cellular atypia, HPV types 6/11 were detected in 62% (8/13), HPV types 16/18 in 46% (6/13), and HPV types 31/33/35 or 51 in 50% (6/12). In about 50% of the biopsies where at least one hybridization method gave a positive result, either one of the commercial methods gave a negative result.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Coinfection of HPV-11 and HPV-16 in a case of laryngeal squamous papillomas with severe dysplasia.

Human papillomavirus (HPV) types 6 and 11 have been associated with benign laryngeal papilloma, while HPV-16 is occasionally associated with laryngeal carcinoma. In this study, a case of laryngeal squamous papillomas with severe dysplasia was evaluated for the presence of HPV infection. The biopsy specimens were taken from a 58-year-old female patient at two different time points 3 months apart. Architecturally, the tumor showed papillary configuration reminiscent of squamous papilloma. Cytologically, the lesion showed morphologic features characteristic of severe squamous epithelial dysplasia. HPV infection was determined by DNA in situ hybridization using type-specific HPV-DNA probes. HPV-11 probes demonstrated homogeneous nuclear staining, suggesting productive viral replication. In contrast, HPV-16 probe produced a speckled pattern, suggesting HPV-16 DNA integration. Normal laryngeal epithelium did not yield specific hybridization. The presence of HPV-11 and HPV-16 was confirmed by PCR using HPV type-specific primers. Immunocytochemical staining was performed to detect Ki-67, a proliferation marker, and p53. Ki-67 expression was demonstrated throughout the whole thickness of epithelium. Staining for p53 was negative. This study suggests that multiple HPV infections can occur in the same lesion and that HPV-16 infection and its DNA integration may contribute to the occurrence of severe dysplasia in the lesion described.

Cell Nucleus↗

Human papillomavirus DNA in adenocarcinoma in situ, microinvasive adenocarcinoma of the uterine cervix, and coexisting cervical squamous intraepithelial neoplasia.

Previously, human papillomavirus (HPV) DNA, mainly HPV-18 DNA, was detected in more than 40% (17/40 cases) of invasive adenocarcinoma of the uterine cervix in our laboratory. In order to identify HPV DNA in the precursor lesions of adenocarcinoma of the cervix, 11 cases of adenocarcinoma in situ containing microinvasive adenocarcinoma and 10 cases of adenocarcinoma in situ were studied for the presence of HPV DNA by in situ hybridization using highly sensitive 3H-labeled HPV-16 and HPV-18 DNA probes. HPV types present in cervical squamous intraepithelial neoplasia (CIN) coexisting with adenocarcinoma in situ and microinvasive adenocarcinoma were also studied. Apart from the coexisting CIN II-III with glandular neoplasms, 48 cases of CIN III (severe dysplasia and squamous carcinoma in situ) removed by conization or hysterectomy and known to be free of adenocarcinoma were used for comparison. HPV DNA was detected in 64% of microinvasive adenocarcinoma, 70% of adenocarcinoma in situ, and 63% of the control CIN III. HPV-18 DNA was the preponderant type of HPV DNA found in adenocarcinoma in situ and microinvasive adenocarcinoma. All cases of HPV DNA-positive microinvasive adenocarcinoma contained the same type of HPV DNA as the lesions of coexisting adenocarcinoma in situ. CIN coexisting with microinvasive adenocarcinoma or adenocarcinoma in situ contained the same type of HPV as identified in the glandular lesions, whereas all of the HPV DNA-positive control CIN III cases contained HPV-16 DNA. These results suggest that adenocarcinoma in situ is a precursor lesion of adenocarcinoma of the cervix that contains HPV DNA, and that CIN coexisting with adenocarcinoma may be a result of a metaplastic process of adenocarcinoma or of bidirectional differentiation of the affected reserve cells.

Adenocarcinoma↗

Human papillomavirus infection and anal cancer.

To study the association of human papillomavirus (HPV) infection with anal cancer, we examined tissue specimens from 126 patients with malignant lesions of the anal skin or mucosa. The patients were enrolled in a population-based, case-control study of ano-rectal cancer which is being conducted in the state of Washington and the Province of British Columbia. Histologic sections from formalin-fixed, paraffin-embedded tissues were tested for the presence of HPV DNA by in situ hybridization with biotin-labelled HPV 6, 11, 16, 18 and 31 DNA probes. HPV DNA sequences were found in tumor tissues from 24 of the 126 subjects (19.0%). When only squamous neoplasms are considered, 23 of 70 subjects (32.9%) had lesions which contained detectable HPV DNA. One HPV-positive patient had a cloacogenic carcinoma that contained regions of squamous differentiation and it was in these squamous cells that HPV DNA was localized. Of the 23 squamous lesions that harbored detectable HPV DNA, 8 contained HPV 6, 10 contained HPV 16, 1 contained HPV 18 and 4 contained an unclassified virus type(s). HPV DNA was found in tissues from 14 patients with carcinoma-in situ and 10 subjects with invasive carcinoma. These results demonstrate that some malignant tumors of the anus, in both men and women, are associated with HPV infection. We conclude that the anal squamous epithelium is another site where infection with the common genital tract HPVs may carry a risk of malignant transformation.

Adenocarcinoma↗

[Detection of human papillomavirus in cutaneous extragenital Bowen's disease in immunocompetent patients].

INTRODUCTION: A specific link between human papillomavirus (HPV) types 16, 18, 31, and 33 and genital carcinomas and between HPV type 5 and cutaneous extragenital carcinomas in patients with epidermodysplasia verruciformis and renal transplant has been previously found. The aim of this prospective study was to detect HPV in cases of cutaneous extragenital Bowen's disease (BD) from non-immunosuppressed patients. PATIENTS AND METHODS: Twelve cases of cutaneous extragenital BD or Bowen's carcinoma (BC), seen in the period 1994-1996 and confirmed by histologic examination, were included in the study. Tissue sections were studied by in situ hybridization with a mixture of HPV DNA probes and specific HPV DNA probes. In addition, study on fresh materiel from 1995 included: Southern blot hybridization with various usual HPV probes (6, 11, 16, 18, 31, 33, 35, 39, 42), polymerase chain reaction (PCR) with hybridization using consensus HPV probes and probes specific for HPV types 6, 11, 16, 18 and 33. In positive samples with conventional PCR, in situ PCR with probes specific for HPV types 6/11 and 16 was performed on tissue sections. RESULTS: In situ hybridization was negative in all the cases. Southern blot hybridization was negative in our 9 studied cases. Three cases studied by consensus PCR were positive. PCR with specific HPV probes revealed positivity on two of these cases: HPV 6 in one, and HPV 16 in another. In situ PCR was positive with a mixed 6/11 HPV probe in the third positive consensus PCR case. DISCUSSION: Our study revealed the presence of HPV in 3 out of 12 cases of cutaneous extragenital BD and BC. HPV type 16, found in BC of skull, was the most usually found type in the literature. HPV types 6/11, detected in 2 cases, were rarely found in cutaneous extragenital BD and BC and these results are in favor of the oncogenic effect of these virus types. In our study, in situ hybridization and Southern blot hybridization were negative in all the cases; HPV was only found in 3 cases by conventional PCR and in 1 case by in situ PCR. The low range of detection of HPV in cutaneous extragenital BD may be due to the used methods, to difficulties related to sampling and/or to a low number of copies of the HPV genoma.

Aged↗

Detection of human papillomavirus (HPV) type 16 and 52b in cervical cancer tissues by Southern blot hybridization and polymerase chain reaction (PCR).

DNA samples from cancer tissues diagnosed histologically as squamous cell carcinoma of the uterine cervix were examined for the presence of human papillomavirus (HPV) genome DNA by Southern blot hybridization. Of 63 specimens, 32 were found to hybridize with HPV DNA probes; 23 specimens (35%) with HPV type 16 (HPV16), one (2%) with HPV type 18 (HPV18), four (7%) with HPV type 52b (HPV52b), and four others (7%) weakly with HPV52b. Specimens negative for HPV DNA with Southern blot hybridization were subjected to polymerase chain reaction (PCR) to determine the presence of HPV DNA under more sensitive conditions. After PCR using one set of primers specific for HPV16 and HPV52b, 7 out of 31 specimens were found to have HPV16 DNA. None was positive for HPV52b DNA. Our results indicate that HPV52b, as well as HPV16 and HPV18, is associated with squamous cell carcinoma of uterine cervix, and more sensitive determination of HPV infection can be made by amplification of the viral genome by PCR.

Base Sequence↗

Detection of human papilloma virus types 16 & 18 DNA in cervical lesions of Indian women using in situ hybridization.

Fifty one biopsies from women with malignant lesions of the uterine cervix and 9 biopsies fron non-malignant lesions were examined for the presence of HPV 16 and 18 DNA sequences by in situ hybridization method using 35S-labelled DNA probes. HPV 16 DNA sequences were detected in 82.4 per cent biopsies from women with malignant lesions, whereas HPV 18 DNA was detected in only 3 biopsies which were also positive for HPV 16 DNA. Two biopsies from non-malignant lesions were positive for HPV 16 DNA only. Data were also analysed according to the histologic type of cancer. It was observed that no significant correlation existed between HPV types and different histologic types of cervical cancer.

DNA Probes, HPV↗

Identification of human papillomavirus DNA in cervical and vaginal intraepithelial neoplasia with molecularly cloned virus-specific DNA probes.

The presence of human papillomavirus (HPV) DNA was identified in the tissues of cervical and vaginal intraepithelial neoplasia by Southern blot DNA hybridization under conditions of low stringency. The specific types of HPV present in the tissues were identified by using molecularly cloned types 1 through 6 (HPV-1 through HPV-6) HPV DNA probes under high-stringency conditions. All tissues of cervical and vaginal intraepithelial neoplasia analyzed contained HPV genomes. Fifteen of 19 samples (79%) contained HPV-6 DNA, and 10 of 19 samples (53%) HPV-3 DNA. Hybridization with HPV-1, HPV-2, HPV-4, and HPV-5 DNAs was also observed in several of the samples. Four of the samples did not hybridize with any of the probes tested (HPV-1 through HPV-6); yet, all showed hybridization with an HPV-EV DNA (a type 3-related DNA) probe under low-stringency conditions, indicating the presence of HPV types other than those belonging to HPV-1 through HPV-6.

Carcinoma in Situ↗

Simultaneous detection and typing strategy for human papillomaviruses based on PCR and restriction endonuclease mapping.

The aim of this study was to devise a simple and reliable method for simultaneous detection and typing of genital human papillomaviruses (HPVs). The method comprises three steps (i) amplification of sample DNA with the L1 consensus primers, (ii) digestion of PCR products with restriction endonuclease RsaI and (iii) hybridization of digested PCR products with a unique oligonucleotide probe that detects different fragments of the six most common genital HPV genotypes, namely, HPV types 6, 11, 16, 18, 31 and 33. Seventeen clinical specimens were analyzed by this method and compared to Southern blot using full genomic HPV DNA probes and to PCR using type-specific probes. All three tests agreed with at least one HPV type; however, the new method identified more additional HPV types in cases of mixed infections.

Base Sequence↗

Prevalence of HPV in a Melbourne female STD population: comparison of RNA and DNA probes in detecting HPV by dot blot hybridization.

A total of 377 women, consecutively selected as first attenders to a sexually transmitted diseases clinic in Melbourne, Australia, were examined for overt Condylomata acuminata and were screened for genital HPV DNA types 6, 11, 16, 18, 31, 33 and (35) using 2 dot blot hybridization methods. Overall, there was a 90% positivity correlation between the 2 methods with HPV DNA being detected in 12% of ectocervical samples. Overt warts were found in 15% of the women and HPV DNA was detected at the cervix in 35% with cytology predicting HPV with or without dysplasia in 27%. Thirteen percent had a past history of warts but none on examination and HPV DNA was evident in 16% while 18% had cytological features of HPV. Those with no warts evident and no past history of warts had both HPV DNA and cytological features of HPV in 7%.

Condylomata Acuminata↗

[Molecular biologic study on the carcinogenesis of HPV in uterine cervical cancer and related lesions--analysis of HPV types 16, 18 E6/E7 gene mRNA].

Recent molecular biologic studies have shown that some type of human papillomavirus (HPV) is closely associated with uterine cervical cancer. In order to investigate the relationship between HPV DNA and cervical cancer, we studied the carcinogenesis of HPV in cervical cancer and related lesions by dot blot hybridization (D.B.H.), Southern blot hybridization (S.B.H.), in situ hybridization (I.S.H.) and polymerase chain reaction (P.C.R.). We also followed some HPV DNA, mRNA positive or negative cases of cervical dysplasia for more than 16 months prospectively. I. Analysis of HPV DNA HPV DNA were detected in cervical dysplasia and cancer and HPV positive rate increased as the grade of cervical dysplasia became higher by several molecular biologic analysis. Especially, the results of I.S.H. with biotinylated HPV DNA probes revealed that HPV DNA was located in the nuclei of koilocytosis, dysplastic cells and cancer cells. In analysis of HPV type in squamous epithelium, HPV 6/11 was the highest positive rate (21.1%) in mild dysplasia. On the other hand, HPV16 positive rate increased with the grade of dysplasia and 34.9% (15/42) of moderate dysplasia and 51.4% (18/35) of severe dysplasia were positive for HPV 16 DNA, respectively. And N/C ratio in HPV 16 positive cells significantly increased by measurement of micrometer. These findings suggest that HPV 16 is high risk HPV and associated with squamous epithelial neoplasia. About 50% of metaplasia close to cervical neoplasia with HPV DNA was positive for the same type of HPV. In columnar epithelium, several types of HPV DNA were detected in 46.7% (15/32) of cervical adenocarcinoma. Thirty one percent (10/32) of adenocarcinoma, 50% (4/8) of adenosquamous cell carcinoma were positive for HPV 18. This suggests an association between HPV 18 and adenocarcinoma and related lesions. We examined amplified DNA detection of HPV 16 and 18 E7 gene by P.C.R. method. HPV 16 and/or 18 DNA were detected in 25 of 43 cases of cervical scrapes obtained from cervical neoplasia, and we confirmed the P.C.R. is the useful method for the screening and the retrospective investigation of HPV infection. By the immunohistochemical and molecular biologic study, there was no correlation HPV DNA with c-myc product and c-myc gene amplification. II. Analysis of HPV mRNA (E6/E7, L1/L2) The early genes E6/E7 of HPV 16 and 18 were considered as one of the carcinogenic factors of uterine cervix. We investigated the localization of HPV E6/E7 and L1/L2 mRNA in cervical dysplasia and CIS with I.S.H. using antisense and sense biotinylated HPV RNA probes which were made by in vitro transcription.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Study on molecular hybridization with biotin-labelled HPV 16 DNA probe in human cervical carcinoma].

Biotin-labelled human papillomavirus (HPV) 16 type DNA probe was prepared by the techniques of molecular biology. And dot hybridization technique was used to detect the HPV 16 homologous sequences in the tissues DNA of human cervical carcinoma. The results indicated that 16 cases out of 28 of the human cervical carcinoma tissues were positive. The positive rate was 57%. The other 4 cases of normal uterine cervix tissues were negative. Only 1 in 4 chronic cervicitis tissues showed positive. The HPV 16 plasmid DNA, as the positive control group, showed strong positive, while lambda-phage DNA was negative. The results have shown that the genome of the HPV actually exists in the tissue of the cervical carcinoma and that there is a close relationship between the cervical carcinoma and HPV infection. This experiment adopted the Biotin-labelled HPV 16 DNA probe. And it may provide us with a quick and sensitive method for investigation of the infection of HPV and its role in the carcinogenesis of cervical carcinoma.

Biotin↗

Detection of human papillomavirus DNA in cell scrapes and formalin-fixed, paraffin-embedded tissue of the uterine cervix by filter in situ hybridisation.

Filter in situ hybridisation (FISH) was used to detect the presence of DNA of human papillomavirus (HPV) types 6/11 or 16/18 in cell scrapes (CYTOFISH) and formalin-fixed, paraffin-embedded biopsies (HISTOFISH) taken from the uterine cervices of 19 women. Paraffin tissue sections collected for HISTOFISH were either digested with pepsin or lysed with alkali/Triton X-100. The digest or lysate of the tissue sections and cell scrapes were applied to nylon or nitrocellulose membranes for nucleic acid hybridisation using 32P-labeled HPV-DNA probes. CYTOFISH and HISTOFISH were compared directly by taking samples for each method from the cervices of the same women. Of 19 women examined by colposcopy, cytology, and histology, eight were assessed as normal and 11 had evidence of a cervical disorder and/or the presence of HPV infection. Whereas no HPV-DNA was detected in the normal cases, the presence of HPV-DNAs was detected by both CYTOFISH and HISTOFISH in 11 cases with histological evidence of HPV infection and/or dysplasia. In these HPV positive cases, eight contained HPV 16/18, two HPV 6/11, and one a mixed infection of HPV 6/11/16/18. The high correlation between the results of CYTOFISH and HISTOFISH shows that formalin-fixed, paraffin-embedded cervical biopsies are suitable specimens for the detection and typing of HPV-DNA by FISH. Both CYTOFISH and HISTOFISH should facilitate studies on the prevalence and distribution of HPVs and their association with neoplasia.

Autoradiography↗

Human papillomavirus (HPV) DNA sequences in oral precancerous lesions and squamous cell carcinoma demonstrated by in situ hybridization.

A series of routinely processed, paraffin-embedded biopsies from 73 surgically treated oral precancerous lesions (OPL) (22 cases), and oral squamous cell carcinomas (SCC) (51 cases), was first screened using an in situ DNA hybridization technique with a human papillomavirus (HPV) DNA probe cocktail containing the 35S-labelled DNA of HPV types 6, 11, 13, 16, 18 and 30. The specific HPV types in lesions shown to contain HPV DNA in this procedure were further analysed by using in situ hybridization and the 6 HPV DNA probes separately. A total of 12/73 (16.4%) of the lesions proved to contain HPV DNA; 6/51 (11.8%) carcinomas and 6/21 (28.6%) dysplasias. The most frequent sites of HPV DNA-positive lesions were palate (4/7; 57%), followed by the floor of the mouth (2/8; 25%), the tongue and gingiva (11.8%). HPV 13 or HPV 30 were not found in any of the lesions studied. HPV 11 DNA was demonstrated in 2 mild dysplasia lesions, but not in carcinomas. One additional mild dysplasia proved to contain HPV 6 DNA. HPV 16 DNA was present in 5 biopsies; 3 carcinomas and 2 dysplasias. In one of the HPV 16-positive carcinomas, HPV 18 DNA was simultaneously present. HPV 18 alone was found in 3 additional carcinomas and in one moderate dysplasia lesion. The results confirm the recently reported evidence on HPV involvement in OPL and oral cancer. The implications of these findings are discussed in terms of the possible HPV etiology of oral SCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗