Usefulness of argyrophilic nucleolar organizer regions score to differentiate suspicious malignancy in pulmonary cytology

OBJECTIVE: Pulmonary cytologic specimens reported as "suspicious for malignancy" pose problems in clinical management. Silver staining for argyrophilic nucleolar organizer regions (AgNOR) has proved useful in making a cytopathologically differential diagnosis between benign and malignant cells. This study aimed to evaluate the usefulness of AgNOR score in the diagnosis of pulmonary cytologic specimens deemed inconclusive by conventional staining methods. METHODS: Pulmonary cytologic specimens initially reported as suspicious for malignancy with Papanicolaou or May-Grünwald-Giemsa (MGG) staining obtained from 35 proved cases were destained then restained using the AgNOR technique. Another 35 cases with clear cytologic diagnosis were also examined for comparison. The median number of dots, defined as the AgNOR score, was used to differentiate malignant from benign specimens. RESULTS: Malignant cases had significantly higher AgNOR scores than benign ones (p<0.001). There were no significant differences among smears previously stained with Papanicolaou or MGG method, among specimens obtained via bronchoscopic brushing, fine-needle aspiration of lung or pleural effusion, or among subgroups of malignant diseases. Based on the results of our previous study, the cutoff value of the AgNOR score to differentiate benignancy from malignancy was set at 6. At this setting, the sensitivity and specificity of AgNOR score were 88% and 80%, respectively, in aiding a differential diagnosis of pulmonary cytologic specimens initially classified as suspicious for malignancy. For those cases with a clear cytologic diagnosis, the sensitivity and specificity of AgNOR score were 92% and 100%, respectively. For all cases, the sensitivity of AgNOR score was 90% and the specificity was also 90%. CONCLUSIONS: The AgNOR score is of value in aiding a differential diagnosis between benign and malignant lesions in pulmonary specimens with equivocal cytologic features.     

Argyrophilic nucleolar organiser regions (AgNORs) in breast lesions

Nucleolar organiser regions (NORs) demonstrated by argyrophilia of NOR-proteins are indicator of cellular proliferative activity. The NORs can be identified in the nuclei as brown or black dots with silver colloidal staining technique in formalin fixed paraffin sections and in cytology smears. Seventy-five cases including 45 tissue sections and 30 fine needle aspiration cytology (FNAC) smears of benign and malignant lesions of breast have been studied to evaluate the significance and practical application of AgNOR count per nucleus. Out of 45 tissue sections 15 belonged to fibrocystic disease, 10 fibro-adenomas and 20 carcinomas and of the 30 FNAC smears, 10 were fibrocystic disease, 8 fibro-adenomas and 12 carcinomas. In fibrocystic disease the mean AgNOR count was 1.60 (FNAC group-0.75, tissue section-1.61). In fibro-adenomas it was 1.61 (FNAC-1.63, tissue section-1.59). The mean count in carcinoma was 12.10 (FNAC-12.08, tissue section-12.10). The difference in AgNOR count in fibrocystic disease and fibro-adenoma was not significant, but that between benign breast lesion and carcinoma was significant. No difference was observed between FNAC and tissue section groups in benign or malignant lesions. The simple staining technique can be used as an additional criterion to differentiate the benign and malignant lesions of breast.     

Improvements in the silver-staining technique for nucleolar organizer regions (AgNOR)

The silver-staining technique for nucleolar organizer regions (AgNOR) of Ploton et al., as popularized by Crocker, is being widely used for evaluation of nucleolar function, especially in neoplasia. It suffers from limited reliability, background staining, precipitates, and fading of the sections. Factors were identified that affect these problems. The oxidation-reduction level and gelatin used are particularly important. An improved procedure is presented which incorporates pre-reduction of the sections, selection of an optimal gelatin, and post-treatment of the sections to produce a permanent preparation. It is compatible with many fixatives and with other stains used before or after the silver stain.     

Functional adrenal cortical tumors in childhood: a study of ploidy, p53-protein and nucleolar organizer regions (AgNORs) as prognostic markers

The Washington State Patrol Crash Database and computerized hospitalization records for 1989-1993 were used to determine total hospital charges billed for motor vehicle collision injuries to drivers whose crash reports contained any indication of alcohol use. In this population-based study, total hospital charges were summed, and mean charges and lengths of stay were computed within alcohol use and insurance coverage status categories in an attempt to evaluate the hospital charges billed to public funding and private insurance. Of the total hospital charges for drivers with injuries from motor vehicle collisions for which a police-reported indicator of alcohol use status was available, 43% (U.S.$64.8 million) were for drivers who reportedly had been drinking. At the time of discharge, Medicaid was identified as the payor for 47% of these hospitalizations. The mean hospital charge billed per collision was greater for drinking (U.S.$18,258) than nondrinking drivers (U.S.$14,181). Drinking drivers also had longer hospital stays, even after adjustment for patient age, gender and injury severity. During this time in Washington state, the average annual amount billed at discharge for initial inpatient care of injuries to drivers who reportedly had been drinking at the time of the motor vehicle collision was U.S.$13 million. This includes only the amount assessed by the hospital at the time of discharge for treatment of the initial injury and does not include other related medical charges for rehabilitation or outpatient care, or for doctors' or laboratory fees. As increasing pressures of managed and capitated care lead to a shift of financial risk from the federal government and insurers to states and providers, the financial burden of specific, potentially preventable conditions such as this will receive greater attention.     

Nucleoli and argyrophil nucleolus organizer regions (AgNORs) of cells of the megakaryocytic line in the rat

The main maturation stages of Norway rat megakaryocytic series, megakaryoblasts and mature megakaryocytes, stained by silver for demonstration of argyrophil nucleolus organizer regions (AgNORs) were investigated to provide basic information on the number of nucleoli and interphasic AgNORs in these cells. The results showed that megakaryoblasts as well as mature megakaryocytes possess numerous nucleoli; their number and also the number of AgNORs is significantly higher in less mature than in more mature cells. The number of AgNORs in megakaryocytes of the Norway rat and man are virtually the same, although the numbers of nucleolar organizers per haploid chromosome set differ markedly. This fact leads to the conclusion that the number of interphasic AgNORs depends on the function and metabolic state of the cell rather than on the number of nucleolar organizers.     

The proliferative activity in oral epithelial dysplasia analyzed by proliferating cell nuclear antigen immunostaining and argyrophilic nucleolar organizer region staining

The proliferative activity of leukoplakia without dysplastic change (LP), epithelial dysplasia (ED), and squamous cell carcinoma (SCC) in the oral mucosa was examined by means of proliferating cell nuclear antigen (PCNA) immunostaining, silver-binding argyrophilic nucleolar organizer region (AgNOR) staining, and the frequency of mitotic figures. Significant differences in the labeling index of PCNA immunostaining (PI) and mitotic index (MI) were noted between LP and ED and between ED and SCC. The mean numbers of AgNORs (AI) significantly differed between ED and SCC. There was a significant positive correlation between PI and MI in samples of ED. However, there was no significant correlation between AI and other indexes. The number and the distribution of PCNA-positive cells in ED varied among samples. Five samples with higher PI and MI indexes than the mean values were selected from those of dysplasia based on the correlation between PI and MI. Their histological features symptomatic of oral ED as defined by the World Health Organization (WHO) Collaborating Centre in 1978, were investigated and compared with 10 samples with lower indexes. Histological findings, such as "loss of polarity of the basal cells," "an increased nuclear-cytoplasmic ratio," "cellular pleomorphism," and "enlarged nucleoli," were significant histological features of these five samples. This study showed that the four histological components described previously and the increased number of mitotic figures used as the index of proliferating activity were the main histological components related to severe ED of oral mucosa. They will provide a useful means of deciding the histopathological grade of oral ED.     

Assessment of the expression of p53, MIB-1 (Ki-67 antigen), and argyrophilic nucleolar organizer regions in carcinoma of the extrahepatic bile duct

Group B streptococci (GBS) are an important cause of neonatal sepsis, pneumonia and meningitis. In the early phase of infection, macrophages and polymorphonuclear cells (PMN) are the first immune cells that interact with GBS. In this in vitro study, to gain insight into GBS-macrophage interaction in the absence of type-specific antibodies, we examined the features of GBS survival in thioglycollate-elicited murine peritoneal macrophages and the effect of GBS on the protein kinase C (PKC)-dependent transduction pathway. Our results demonstrate that type Ia GBS, strain 090 (GBS-Ia) and type III GBS strain COH 31r/s (GBS-III), after in vitro phagocytosis survive and persist intracellularly in macrophages for up to 24 and 48 hr, respectively. However, macrophage activation by interferon-gamma (IFN-gamma) and lipopolysaccharide from Escherichia coli (LPS) caused a significant reduction in the time of intracellular persistence. Macrophage activation by IFN-gamma and LPS seems to be a multifactorial event involving multiple intracellular signal pathways also including PKC. Since PKC is one of the components in the signal network leading to macrophage activation and an important target for several intracellular micro-organisms, we wondered whether PKC could have a role in intracellular GBS survival. Both PKC depletion by treatment with phorbol 12-myristate 13-acetate (PMA) for 18 hr and PKC inhibition by Calphostin C rendered macrophages more permissive for the intracellular GBS survival. Furthermore, GBS-infected macrophages were unable to respond to PMA and LPS, activators of PKC, by inducing antimicrobial activity. The ability of GBS to impair PKC-dependent cell signalling was also demonstrated by the reduced c-fos gene expression in GBS-infected macrophages with respect to control macrophages, after LPS stimulation. In conclusion, our results indicate that GBS survive in macrophages and impairment of PKC signal transduction contributes to their intracellular survival.     

Effects of sex steroids on silver stained proteins of nucleolar organizer regions (Ag-NOR) in the rabbit uterus

Silver staining of argyrophilic proteins of nucleolar organizer regions (Ag-NOR) has been used to evaluate a hyperactive state of cells. We studied the effects of sex steroids on the Ag-NOR proteins in the rabbit uterus. Estradiol-17beta (E2) caused uterine hypertrophy and increased the number of Ag-NOR dots in epithelial and stromal cells of the endometrium and smooth muscles cells in a dose dependent manner without proliferative change in the endometrium. Progestins including progesterone, medroxyprogesterone acetate (MPA), and norethindrone following E2 caused progestational proliferation of the endometrium with an increase in the Ag-NOR number to various extents, whereas methyltestosterone, a synthetic androgen, caused only a minimal proliferative change in the endometrium without an increase in the Ag-NOR number. Western blot analysis revealed that progesterone and MPA increased the amounts of a 100 kDa protein (nucleolin) and a 37 kDa protein (B23 protein) in the endometium and a marked proliferative change, whereas E2 did not. These results suggest that although the Ag-NOR number was enhanced by both progestin and estrogen, only progestins substantially increase the Ag-NOR protein in the rabbit uterus. This implies that an increase in the amount of nucleolin and B23 protein is associated with the proliferative potential of the cells.     

Detection of human papillomavirus DNA sequences in oral squamous cell carcinomas and their relation to p53 and proliferating cell nuclear antigen expression

BACKGROUND: The etiology of oral squamous cell carcinoma (SCC) is still obscure. Since human papillomavirus (HPV) DNAs are associated with carcinoma of the uterine cervix, carcinomas of the oral cavity were investigated to ascertain if these viruses are present in squamous carcinomas of this anatomic site. METHODS: Seventy-seven oral mucosal SCCs were examined for the presence of HPV DNAs by polymerase chain reaction and dot blot hybridization. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and p53 was performed and single strand conformation polymorphism analysis for p53 was undertaken. In situ hybridization detection of HPV-16 DNA also was performed. RESULTS: Human papillomavirus-16 DNA was detected in 23 cases of oral SCC and both HPV-16 and HPV-18 DNA were detected in one case of tongue SCC. Human papillomavirus DNAs were detected of 11 of 33 tongue, 4 of 15 gingival, 2 of 4 palate, 2 of 5 buccal mucosa, 3 of 7 maxillary sinus, and 2 of 11 the floor of the mouth SCCs. None were detected in SCCs of the retromolar region (0/2). Immunohistochemical examination for p53 was performed in 26 cases of oral SCC and the accumulation of p53 protein was observed in 6 cases (i.e., in 4 of 17 HPV DNA-negative cases and in 2 of 9 HPV DNA-positive cases). Single strand conformation polymorphism analysis confirmed gene mutations in all 6 cases. Human papillomavirus-16 DNA was predominantly identified in cancer cells that showed a morphologic resemblance to basal cells and its hybridized signal in keratinized cells was reduced by in situ hybridization detection. Immunohistochemical detection of PCNA revealed its cooccurrence with HPV-16 DNA in cancer cells. CONCLUSIONS: These results suggest that HPV-16 DNA sequences may have the capability to maintain the proliferative state of epithelial cells, and may contribute to the production of malignant phenotypes.     

Argyrophilic nucleolar organizer regions staining is useful in predicting recurrence-free interval in oral tongue and floor of mouth squamous cell carcinoma

BACKGROUND: Argyrophilic nucleolar organizer regions (AgNORs) represent a tissue marker of cell proliferative activity. The purpose of this study was to assess the prognostic value of AgNORs expression in oral squamous cell carcinoma (SCC). METHODS: The AgNORs area/nucleus was studied in paraffin sections by means of digital image analysis in 43 cases of stage II oral tongue and floor of the mouth SCC. RESULTS: Time free of disease was considered a dependent variable of a binary indicator of AgNORs expression (7.77 microns2/nucleus as a cut-off point). High AgNORs level was associated with a statistically significant negative effect on recurrence-free interval of disease in a Cox proportional hazards models controlled for occult lymph node metastasis, involvement of the surgical margins, thickness of the lesion, and vascular invasion. CONCLUSIONS: The AgNORs area increased the capability of predicting which patients have a high risk of recurrence of cancer, and its evaluation may provide useful information for the therapeutic approach to the oral tongue and floor of the mouth SCC.     

Study of organizer nucleolar regions by the argyrophil technique in cervical intraepithelial neoplasias

Thirty three biopsies of the uterine cervix were studied by the AgNOR method, that identifies the nucleolar organizer regions. These comprised 9 cases of cervicitis (with or without squamous metaplasia), 9 cases of cervical intraepithelial neoplasia grade I (CIN I), 8 CIN II and 10 CIN III. A hundred cells were counted and classified according to the number of AgNOR dots. We use a more practical and fast method of AgNOR dots counting in cervical intraepithelial neoplasia, in that we exclude the two basal layers and count only cells with 4 or more dots. Statistically significant differences for AgNOR dots were found between cervicitis or CIN I and CIN II cases (p < 0.02) and between CIN II and CIN III cases (p < 0.001). No statistical difference was found between the cases of cervicitis and CIN I. It was concluded that this method of AgNOR counting can be useful in the identification and classification of individual cases intraepithelial neoplasia and their differentiation from eventual difficult cases of cervicitis.     

Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection

BACKGROUND: Experimental models and analyses of human tumors suggest that oncogenic, sexually transmittable human papillomaviruses (HPVs) are etiologic factors in the development of oral squamous cell carcinoma (SCC). We conducted a population-based, case-control study to determine whether the risk of this cancer is related to HPV infection and sexual history factors. METHODS: Case subjects (n = 284) were 18-65-year-old residents of three counties in western Washington State who were newly diagnosed with oral SCC from 1990 through 1995. Control subjects (n = 477) similar in age and sex were selected from the general population. Serum samples were tested for HPV type 16 capsid antibodies. Exfoliated oral tissue collected from case and control subjects and tumor tissue from case subjects were tested for HPV DNA. Odds ratios (ORs) were calculated after adjusting for age, sex, cigarette smoking, and alcohol consumption. RESULTS: Among males only, oral SCC risk increased with self-reported decreasing age at first intercourse, increasing number of sex partners, and a history of genital warts. Approximately 26% of the tumors in case subjects contained HPV DNA; 16.5% of the tumors contained HPV type 16 DNA. The prevalence of oncogenic HPV types in exfoliated oral tissue was similar in case and control subjects. The ORs for HPV type 16 capsid seropositivity were 2.3 (95% confidence interval [CI] = 1.6-3.3) for all oral SCCs and 6.8 (95% CI = 3.0-15.2) for oral SCCs containing HPV type 16 DNA. The joint association of cigarette smoking and HPV type 16 capsid seropositivity with oral SCC (OR = 8.5; 95% CI = 5.1-14.4) was stronger than predicted from the sum of individual associations with current smoking (OR = 3.2; 95% CI = 2.0-5.2) and seropositivity (OR = 1.7; 95% CI = 1.1-2.6). CONCLUSIONS: HPV type 16 infection may contribute to the development of a small proportion of oral SCCs in this population, most likely in combination with cigarette smoking.     

Cytogenetic of nucleolar organizer regions (NOR) of human chromosomes: identification of four morphofunctional variants of NOR, their inter-individual and inter-chromosomal distribution

Cytogenetic characters of the nucleolus organizer regions (NORs) located on the short arms of five acrocentric chromosomes were studied in chromosome preparations obtained from cultured blood cells of 17 donors. In situ hybridization to a 3H-labeled probe was used to estimate the relative copy number of ribosomal genes (RGs) in all NORs of chromosomes identified by G-banding in each sample. The relative amount of potentially active RGs (0 to 4 arbitrary units) in each NOR was estimated from the size of AgNOR selectively stained with silver nitrate. Linear regression analysis revealed clusters of silent RGs (CSRGs) in 24 out of 170 NORs (14%). Based on the presence or absence of active and inactive RG clusters, NORs of human chromosomes were classified into four morphological functional variants (MFVs): (1) Ag-/CSRG-, (2) Ag-/CSRG+, (3) Ag+/CSRG-, and (4) Ag+/CSRG+. These variants were observed in 7.65%, 2.35%, 11.8%, and 78.2% of 170 analyzed NORs, respectively. NORs with CSRGs (MFV 2 and 3) were absent in 5 out of 17 donors. One, two, and three NORs with CSRGs were observed in four donors each. Analysis of the chromosome distribution of NOR MFVs showed that their frequencies remained almost the same in group-D and group-G acrocentric chromosomes. Although the tested samples were small (34 chromosomes for each pair), two observations were made with regard to individual chromosomes. First, almost half MFV-1 NORs (6 out of 13) were detected on chromosome 15. Second, the frequency of CSRGs was higher in chromosome 21 (29%) than in the other chromosomes (10%).     

Number of nucleoli and nucleolar organizer regions per nucleus and nucleolus--prognostic value in canine mammary tumors

The carbohydrate residues of the surface coat of 20 axenic cultures of Blastocystis hominis were studied using FITC-labelled lectins (ConA, WGA, DBA, HPA, SBA, PNA, UEAI and LPA). The specific affinity of reactive lectins was determinated by competitive inhibition assay with specific carbohydrates or by enzymatic pre-treatment of cells. All stocks strongly bound ConA and HPA; WGA, UEAI and LPA were partially reactive, and the remaining lectins were nonreactive. Inhibition assays showed abolition (WGA, LPA, UEAI and HPA) or partial reduction (ConA) of lectin affinity, which demonstrated the specificity of binding assay. These results indicate that B. hominis has surface components containing alpha-D-mannose, alpha-D-glucose, N-acetyl-alpha-D-glucosamine, alpha-L-fucose, chitin and sialic acid.     

Cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection

Many studies have shown a strong correlation between CIN and HPV infection. Molecular biology has allowed identification of types of HPV which seem to be connected, more frequently than others, to dysplastic lesions. Physical state of HPV-genome seems to play an important role in the development of cervical cancer. In this study the HPV-genome has been searched in tissue specimens obtained from 34 women affected by CIN II and III. All patients underwent laser conization. Immediately before treatment, colposcopically directed biopsies of the cervical lesion and of the areas with no colposcopically apparent disease were taken and on these samples, HPV-DNA has been searched, isolated and analysed for HPV types and physical state. Histologic examination on cones showed 6 cases of CIN II (3 with HPV), 24 cases of CIN III (14 with HPV), 1 microinvasive carcinoma and 3 with no residual lesion. Southern blot analysis detected HPV-DNA in 4 cases of CIN II (16.7%) and in 20 cases of CIN III (70.6%). In 50% of CIN II and 85% of CIN III HPV 16 DNA has been found and in the remaining 50% of CIN II and 15% of CIN III HPV 31 DNA has been detected. All CIN II and 14 cases of CIN III showed episomal HPV-DNA. Integrated HPV-DNA has been found in 3 cases of CIN III and the other 3 cases of CIN III showed both integrated and episomal HPV-genome. Integrated form has been noticed only for HPV 16 type. In no case of colposcopically normal tissue has HPV-DNA been found. These data seem to confirm the strong correlation between HPV 16 type, which often has integrated form, and CIN III strengthening the hypothesis of its potential oncogenic action.     

High-resolution GTG-banding and nucleolar organizer regions of chromosomes of two vole species: Microtus rossiaemeridonionalis and M. transcaspicus (Rodentia, Arvicolidae)

Two lines of White Leghorns that had undergone long-term selection for high (HH) or low (LL) antibody response to sheep red blood cell antigen(s) formed the nuclear lines for this experiment. Matings were made in a full diallel cross to produce in a single hatch from age-contemporary breeders the parental lines, reciprocal F1 and F2 crosses, and backcrosses for 16 progeny types. For males and females, there were parental line differences in BW to 42 d of age, after which there was decline between lines for males. Differences in BW between reciprocal F1 crosses and maternal heterosis declined with age, primarily reflecting dissipation of effects of egg weight. Heterosis of BW was dependent on the particular F1 cross and recombination effects were not important. At 50 d of age chicks were inoculated with either a 1 or 10% suspension of spleen extract from chickens infected with marble spleen disease virus (MSDV). A third group served as uninjected controls. Response to MSDV was evaluated by spleen weight 6 d after inoculation. Spleen weights relative to BW of control chicks were heavier for the HH than LL line with evidence from the crosses of sexlinkage and negative heterosis. Line LL chicks were more resistant to MSDV than Line HH chicks was F1 crosses intermediate to and different from either parental line with no evidence of heterosis.     

p53 alteration, proliferating cell nuclear antigen, and nucleolar organizer regions in thymic epithelial tumors

We examined p53 protein expression, p53 gene mutation, proliferating cell nuclear antigen (PCNA), and argyrophilic nuclear organizer regions (AgNOR), in 30 patients with surgically-treated thymic tumors (26 thymoma and 4 thymic carcinoma cases). p53 expression ratio with DO-1 was divided as p53 negative (0% positivity), low expressor (<10% positivity), high expressor (>10% positivity). The incidence of p53 low and high expressor in thymoma were 19% (5/26) and 8% (2/26), respectively. p53 immunopositivity in thymoma was significantly correlated with PCNA labeling index (LI). p53 expression ratio in invasive thymoma (33%) tended to be higher than that in non-invasive thymoma (18%). p53 expression was detected in one of the thymic carcinoma. There were no p53 gene mutations in 15 invasive thymoma, although one of four (25%) thymic carcinomas showed two point mutations. p53 gene alterations seem to be associated with malignant activity of tumor cells, and therefore detection of p53 gene mutations is useful as a diagnostic factor.     

Expression of keratin 13, 14 and 19 in oral squamous cell carcinomas from Sudanese snuff dippers: lack of association with human papillomavirus infection

In stratified squamous epithelia, altered expression of keratins (Ks) is one possible marker of malignant potential. In the epithelium of the uterine cervix, presence of human papillomaviruses (HPVs) is increasingly regarded as a marker of risk for cervical cancer. However, a similar role in oral cancer and precancer remains controversial. To address these questions, formalin-fixed, paraffin-embedded oral carcinomas from Sudanese snuff dippers (n=14) and oral carcinomas from Sudanese (n=14), Swedish (n=19) and Norwegian (n=41) non-snuff dippers were examined by immunohistochemistry for expression of K types 13, 14 and 19 using monoclonal antibodies. HPV infection was searched for in all the carcinomas by in situ hybridization (ISH) using the cocktail HPV OmniProbe and the ViraType probe. Carcinomas from Sudanese (snuff dippers/non-snuff dippers) were also examined for HPV infection by polymerase chain reaction (PCR) using the general HPV primers GP5+/GP6+. For the oral carcinomas from snuff dippers, moderate to intense expression of K13 (71%; 10/14), K14 (86%; 12/14) and K19 (93%; 13/14) was found. For the oral carcinomas from non-snuff dippers, weak to moderate expression of K13 (64%; 47/74), K14 (43%; 32/74) and K19 (45%; 33/74) was found. HPV DNA was not detected in any of the carcinomas from three countries when examined by ISH. The Sudanese (from snuff dippers/non-snuff dippers) oral carcinomas were also negative for HPV DNA with the PCR. The present study shows that (i) there is a high level of expression of K13, K14 and K19 in oral carcinomas from snuff dippers compared to those from non-snuff dippers, (ii) this high level of expression may arise from dysregulation of keratinocyte proliferation and maturation caused by damaging effects of snuff, (iii) the HPV genome is not found in Sudanese (snuff dippers/non-snuff dippers), Swedish or Norwegian oral carcinomas, and (iv) this may suggest that these viruses do not play a prominent role in the aetiology of oral carcinomas from these countries.     

Detection of human papillomavirus DNA and clinicopathological study of vulvar human papillomavirus infection

We studied 217 vulvar HPV infection patients by clinically, pathologically, and virologically. From 90.6% of the cauliflower-like vulvar lesions and 29.7% of the papillomatous and finger-like lesions, we detected HPV 6/11 DNA by dot blotting hybridization. The patients in 90.0% of the cauliflower-like group and 9.8% of the papillomatous and finger-like group had a high risk factor to intercourse with different sex partners (P < 0.0001). The pathological characteristics, nature history, and response to treatment were different. According to clinical, pathological, and virological findings divided three types: vulvar HPV infection type 1 (or condylomata acuminata), vulvar HPV infection type 2, and vulvar HPV infection type 3.     

Studies of human papillomavirus infection (HPV) and expression of oncoprotein p 21 in cervix neoplasms

Frequencies of HPV type 16 and 18, evaluated by in situ hybridization technique in uterine cervix carcinomas of the IIIrd stage of clinical advancement, were 54% and 36.5% respectively. Presence of p 21 protein was detected in 85.3% cases of the cancers and showed no relation to HPV infection.