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K V Shah

Publications and source records attributed to K V Shah.

At least 73 records · Page 4Linked to original sources
PubMed1996

Human papillomavirus-specific serologic response in vulvar neoplasia.

Epidemiological and virological evidence suggests that invasive squamous cell carcinoma (SCC) of the vulva is etiologically heterogeneous and that basaloid or warty SCC (BWSCC) and vulvar intraepithelial neoplasia (VIN) are linked to human papillomavirus (HPV) infections while keratinizing SCC (KSCC) is a non-HPV-associated malignancy. In the present study, HPV-specific antibodies in sera of patients with BWSCC, VIN, and KSCC and of controls were examined by ELISA for antibodies reactive to HPV-16 virus-like particles (VLP) and in radioimmunoprecipitation assays for antibodies to HPV-16 E6 and E7 proteins expressed by in vitro transcription and translation. The prevalences of antibodies to HPV-16 VLPs were significantly higher in HPV-associated VIN (59.1%) and BWSCC (50.0%) than in KSCC (22.2%) and controls (18.2%). Antibodies to E6 and E7 proteins were more prevalent in BWSCC than in any other groups. Prevalence of serum antibodies to any one of the antigen preparations was significantly higher in BWSCC (64.3%) and VIN (59.1%) than in KSCC (27.8%) and controls (22.2%). Also, sera with high antibody titers were found more frequently in BWSCC and VIN cases than in controls. These data provide immunological evidence in support of the observation that VIN and BWSCC, but not KSCC, are associated with HPV infections.

Aged↗
PubMed1996

Heterogeneous etiology of squamous carcinoma of the vulva.

OBJECTIVE: To correlate various previously identified risk factors, different histologic types, and the presence of human papillomaviruses (HPV) in squamous vulvar carcinomas and intraepithelial precursor lesions. METHODS: Cases of squamous vulvar carcinomas and intraepithelial precursor lesions from a case-control study were analyzed by histologic type, the presence of HPV, and HPV type. These findings were correlated with demographic and interview data. RESULTS: Significant differences (P < .001) in the prevalence of HPV DNA were noted between the following: 1) patients with high-grade vulvar intraepithelial neoplasia (VIN) (48 of 54 [88.9%]), 2) different types of squamous carcinomas, designated basaloid and warty carcinomas (18 of 21 [85.7%]), and 3) keratinizing squamous carcinoma (three of 48 [6.3%]). When the risk factor profiles for basaloid or warty carcinoma and keratinizing squamous carcinoma were compared, it was found that basaloid and warty carcinoma was significantly associated with the classical cervical cancer risk factors (lifetime number of sexual partners, age at first intercourse, abnormal Papanicolaou smears, venereal warts, low socioeconomic status, and cigarette smoking) whereas keratinizing squamous carcinoma was less strongly linked to these factors and in some cases not at all. The risk profile for VIN was similar to that of basaloid and warty carcinoma (with respect to sexual and reproductive history and smoking), although effects were weaker for some factors. CONCLUSION: The results of this study further support the view that vulvar carcinoma has two different etiologies, one related to HPV infection and one that is not.

Adult↗
PubMed1996

Cervical abnormalities, human papillomavirus, and human immunodeficiency virus infections in women in Malawi.

Cervical lavage samples and Pap smears were obtained from 284 women in Malawi to evaluate the association between human papillomavirus (HPV) and human immunodeficiency virus (HIV) infections. Squamous intraepithelial lesions were present in 15% (17/16) of HIV-seropositive and 7% (11/152) of HIV-seronegative women (P=.05) and in 23% (19/83) of HPV polymerase chain reaction (PCR)-positive and 4% (6/156) of HPV PCR-negative women (P<.001). HPV DNA was detected in 23% of HIV-uninfected women but in 60% of HIV-infected women with <300 CD4 cells/mm(3) (P<.002). High-risk HPV types 16 and 18 constituted half of the identified types. HPV DNA in previously HPV-positive women was detected more often than in HIV-seropositive abnormal cervical cytology than uninfected ones and were more likely to have persistent HPV infections. Early detection of HPV and regular monitoring of HIV-related cervical lesions may be important in HIV-infected women.

DNA, Viral↗
PubMed1996

Human papillomavirus investigation of patients with cervical intraepithelial neoplasia 3, some of whom progressed to invasive cancer.

The major objective of the study was to determine if the contrasting frequencies (1.5% vs. 22%) of progression of cervical intraepithelial neoplasia (CIN) 3 lesions to invasive cervical carcinoma in two groups of patients in a previously published study from New Zealand had a virologic basis. Archival tissues on which the original diagnosis of CIN 3 was made were examined. Paraffin sections of 81 CIN 3 lesions from each group were tested for the presence of human papillomavirus (HPV)-6, -11, -16, and -18 DNA sequences by a combination of in of in situ hybridization for viral transcripts and polymerase chain reaction for viral DNA. The virologic profiles of the two groups were similar; HPV-16 and HPV-18 were identified, respectively, in 62% and 6% of CIN 3 lesions of group 1 and in 60% and 2% of CIN 3 lesions of group 2. additional tissues were examined for 17 women of group 2, who progressed from CIN 3 invasive cancer. Progression to invasive cancer was not associated with infection with specific HPV types. It is concluded that the contrasting frequencies of progression to invasive carcinoma in two groups of New Zealand women were not attributable to differences in HPV type distribution in the original CIN 3 lesions of these two groups.

Adult↗
PubMed1996

Socioeconomic differences in cervical cancer: two case-control studies in Colombia and Spain.

OBJECTIVES: This study examined the causes of socioeconomic differences in invasive cervical cancer in two countries that differ substantially in cervical cancer incidence and economic development. METHODS: Data were derived from two case-control studies carried out in Spain and Colombia; there were 373 case subjects, 387 control subjects, and 425 husbands interviewed with a structured questionnaire. Exfoliated cells were obtained from cervical or penile scrapes and tested for human papillomavirus (HPV) DNA. RESULTS: Relative to better educated women, women with low educational levels in both countries reported fewer Pap smears and had a higher prevalence of HPV DNA. The prevalence ratio of HPV DNA across educational strata was twofold in Spain and fourfold in Colombia. In both countries, husbands of poorly educated women reported higher use of prostitutes than husbands of better educated women. In Colombia, 30% of husbands of poorly educated women harbored HPV DNA, compared with 10% of husbands of better educated women. CONCLUSIONS: Socioeconomic differences in invasive cervical cancer could be partly explained by differences in the prevalence of HPV DNA and by a lower use of preventive care.

Adult↗
PubMed1996

Simian virus 40 and pleural mesothelioma in humans.

It has been reported that DNA of SV40, a virus of Asian macaques that is tumorigenic for rodents and can transform human cells in vitro, is present in pleural mesotheliomas and in several other cancers. To verify these observations, we tested paraffin sections from mesothelioma tissues of 50 patients for SV40 DNA using PCR with two separate sets of primers. The analytic sensitivity for detection of SV40 DNA was 1-10 genome copies. We also tested the specimens for beta-globin by PCR to assess the suitability of the specimen DNAs for amplification. beta-Globin amplification was detected in 48 of the 50 specimens, but SV40 DNA was not detected in any tumors, with either of two SV40 primer sets. Furthermore, sera from 34 additional patients with mesothelioma, 33 patients with osteosarcoma (another cancer reported to be SV40-related) and 35 controls were tested for SV40 antibodies by a plaque neutralization assay. The serological data, like the DNA results, did not support an association of SV40 with mesothelioma or with osteosarcoma; antibodies to SV40 were detected in three mesothelioma patients, in one osteosarcoma patient, and in one control. These findings call into question the association of SV40 with mesothelioma.

Adult↗
PubMed1995

Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group.

BACKGROUND: Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries. There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation. PURPOSE: Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types. METHODS: More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries. Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics. We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types. A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity. RESULTS: HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries. HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5%. HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common. There was significant geographic variation in the prevalence of some less common virus types. A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America. In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors). CONCLUSIONS: Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide. They also suggest that most genital HPVs are associated with cancer, at least occasionally. IMPLICATION: The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs.

Adult↗
PubMed1995

Report of three new cases of squamous carcinoma of the endometrium with emphasis in the HPV status.

Primary squamous cell carcinoma of the endometrium is exceedingly rare. Only 31 cases that fulfill Fluhmann's criteria have been reported in the literature. We report three cases of primary squamous cell carcinoma of the endometrium. In two of the three cases, estrogen receptor (ER) and progesterone receptor (PR) status were analyzed. Only one case contained ER/PR. Additionally, in situ hybridization was performed to determine the presence of human papillomavirus (HPV) in these cases. HPV was not detected in these three cases of primary squamous cell carcinoma of the endometrium.

Aged↗
PubMed1995

Serologic response to human papillomavirus type 16 (HPV-16) virus-like particles in HPV-16 DNA-positive invasive cervical cancer and cervical intraepithelial neoplasia grade III patients and controls from Colombia and Spain.

A human papillomavirus (HPV) type 16 virus-like particle-based ELISA was used to assess antivirion immune responses in 300 women participating in cervical cancer case-control studies in Colombia and Spain. Virion IgG antibodies were detected in the sera of 51% and 59% of women with HPV-16 DNA-positive invasive cervical cancer and 81% and 73% of women with HPV-16 DNA-positive cervical intraepithelial neoplasia grade III (CIN III) in Colombia and Spain, respectively. Capsid antibodies were detected in 22% and 3% of cancer controls (P < .001) and in 43% and 10% of CIN III controls (P = .010) from Colombia and Spain, respectively. Since Colombia has an 8-fold higher incidence of cervical cancer, these results demonstrate an association between ELISA positivity and cancer risk. Capsid antibody responses did not correlate with humoral responses of the same women to HPV-16 E6 and E7 oncoproteins.

Antibodies, Viral↗
PubMed1995

Antibodies to the E4, E6, and E7 proteins of human papillomavirus (HPV) type 16 in patients with HPV-associated diseases and in the normal population.

In a cross-sectional study, titers of antibodies to the E4 and E7 proteins of human papillomavirus (HPV) type 16 were measured by peptide-based enzyme-linked immunosorbent assay in 1707 sera. Sera were obtained from healthy individuals (ages 1 to 95 years), from patients with HPV-associated infection (cervical intraepithelial neoplasia and cervical cancer), and from patients who were at high risk for HPV infection (attending a sexually transmitted disease clinic or referred to a colposcopist because of an abnormal Papanicolaou smear). The prevalence of anti-E7 antibodies increased with age, although the overall prevalence in the adult population was low (10.36%) compared to the frequent detection of HPV 16 DNA in the population. This suggests that only a fraction of patients infected with HPV 16 develop an anti-E7 response. The age distribution of anti-E4 antibodies showed a different pattern, i.e., the prevalence was low in the adult population (1.14%) but exceeded 20% in children and teenagers. As the specificity of the anti-E4 reaction was supported by a highly significant association with anti-E6 positivity in children's sera (p = 0.002), it was assumed that infection with HPV 16 can occur frequently early in life. As compared to healthy controls, patients at high risk for HPV infection had a significantly higher frequency (p < 0.001) of antibodies to the HPV 16 E4 protein (but not to the E6 or the E7 protein) in their sera. Therefore, we conclude that in adults E4-specific antibodies may be a marker for virus replication.

Adenovirus E4 Proteins↗
PubMed1995

Accuracy and interlaboratory reliability of human papillomavirus DNA testing by hybrid capture.

Epidemiologists and clinicians wishing to introduce human papillomavirus (HPV) testing into cervical cancer prevention programs need standardized, reliable, and accurate HPV DNA tests that can detect the full spectrum of pathogenic HPV types. The Hybrid Capture System assay from Digene (hybrid capture assay) is a nonradioactive kit designed to detect 14 HPV types in two groups: a mix of 9 high-risk types associated with anogenital cancer (HPV types 16, 18, 31, 33, 35, 45, 51, 52, and 56) and another group of 5 low-risk types associated with condyloma acuminatum (HPV types 6, 11, 42, 43, and 44). The assay yields quantitative data meant to reflect viral concentration. In a study of 199 cervical specimens from women with concurrent Pap smears, we assessed the reliability of the new assay by comparing the hybrid capture assay results from three laboratories. We assessed the accuracy of the hybrid capture assay in comparison with a reference standard of HPV DNA content (multiple testing by several methods in two reference laboratories). We also compared the hybrid capture assay results with the concurrent cytologic diagnoses on the basis of an independent review of each smear by five pathologists. Pairwise interlaboratory agreement rates on HPV positivity for either high-risk or low-risk types ranged from 87 to 94%, and kappa values ranged from 0.61 to 0.83. Among specimens positive for high-risk types (the most important clinical outcome), the interlaboratory correlations of the quantitative data ranged from 0.60 to 0.90. Test results from all three laboratories were strongly associated with those of the HPV DNA reference standard and with the concurrent cytopathologic diagnoses. The most common errors were sporadic, apparently false-positive results.

Cervix Uteri↗
PubMed1994

The role of HPV in the etiology of cervical cancer.

To assess the association between human papillomavirus (HPV) and cervical cancer we have carried out two case-control studies of cervical intraepithelial neoplasia grade III (CIN III) (525 cases and 512 matched controls) and two case-control studies of invasive squamous cell carcinoma (436 cases and 387 population controls) in Cali, Colombia and nine provinces of Spain. HPV DNA detected by polymerase chain reaction, a PCR-based hybridization assay in the exfoliated cells of the uterine cervix, was the strongest risk factor in both countries. For invasive cancer the adjusted odds ratios and 95% confidence intervals were: 46.2 (18.5-115.1) in Spain and 15.6 (6.9-34.7) in Columbia and for CIN III they were: 56.9 (24.8-130.6) in Spain and 15.5 (8.2-29.4) in Columbia. This strong association was specific for types 16, 18, 31, 33 and 35 and also for HPV types not yet characterized. Hormonal factors such as oral contraceptives and high parity appear to confer an additional risk increasing the progression from chronic HPV infection to cancer. Our overall results indicate that HPV is the main cause of cervical cancer in two countries with contrasting rates of cervical cancer, Columbia having an incidence rate about 8 times higher than Spain.

Adolescent↗
PubMed1994

Lack of association of human polyomaviruses with human brain tumors.

Brain tumors, primarily glioblastoma multiforme, were examined for the presence of BKV DNA. DNAs extracted from 33 fresh-frozen tumors and from an additional 47 paraffin-embedded tumor tissues were tested for BKV sequences using two different primer pairs. One primer pair amplified highly conserved sequences in the early region coding for BKV and JCV T antigens. The other primer pair amplified the regulatory region of BKV-IR, a variant previously associated with human brain tumors. None of the tumors were positive for BKV or JCV DNA.

Base Sequence↗
PubMed1994

Comparison of peptide enzyme-linked immunosorbent assay and radioimmunoprecipitation assay with in vitro-translated proteins for detection of serum antibodies to human papillomavirus type 16 E6 and E7 proteins.

Antibodies to human papilloma virus (HPV) type 16 (HPV-16) E6 and E7 proteins in serum are markers for HPV-associated invasive cervical carcinoma. We compared two assays, a radioimmunoprecipitation assay with in vitro-translated HPV-16 E6 and E7 proteins and an enzyme-linked immunosorbent assay (ELISA) with E6 and E7 synthetic peptides, for their abilities to discriminate serologically between patients with invasive cervical cancer and controls. Among the patients, antibody prevalences were higher by the E6 radioimmunoprecipitation assay (55.7%) than by the E6 peptide ELISA (15.5%), but among the controls, they were lower by the radioimmunoprecipitation assay (1.7%) than by the E6 peptide ELISA (5%). For E7, antibody prevalences among the patients were comparable by the radioimmunoprecipitation assay (43%) and the peptide ELISA (41%), but among the controls they were higher by the E7 peptide ELISA (17.4%) than by the radioimmunoprecipitation assay (4.1%). There was good agreement between the E7 radioimmunoprecipitation assay and the E7 peptide ELISA among patients but not among controls. In tests with representative sera, heat denaturation of the translated proteins resulted in a complete loss of reactivity to the E6 protein and a marked decrease in reactivity to the E7 protein. Our study showed that the radioimmunoprecipitation assay discriminates better than the peptide ELISA between patients with invasive cervical cancer and controls and that this is related to the ability of the radioimmunoprecipitation assay to detect conformational epitopes.

Antibodies, Viral↗
PubMed1994

Human papillomavirus-related serological markers of invasive cervical carcinoma in Brazil.

Masked sera from 194 cases and 217 controls participating in a case-control study of cervical cancer in Brazil were examined for antibodies to human papillomavirus (HPV) 16 E6 and E7 by radioimmunoprecipitation assay. Radiolabeled full-length E6 and E7 proteins expressed by in vitro transcription and translation in rabbit reticulocyte lysate were used as antigens. The antibody prevalences in cases and controls were: 54.1% versus 6% for E6; 30.4% versus 4.6% for E7; 63.4% versus 10.1% for either E6 or E7; and 21.1% versus 0.5% for both E6 and E7. The corresponding odds ratios were 35 ([95% confidence interval (CI)], 15-83), 10 (95% CI, 4-25), 28 (95% CI, 13-61) and 87 (95% CI, 10-736). The most marked contrast between cases and controls was observed for sera with high antibody titers (cpm > 6000) with an odds ratio of 239 (95% CI, 29-1946) for E6 or E7. Seroreactivity in cases was partially type specific; women who had HPV-16 DNA in the genital tract had higher antibody prevalence rates than those who were negative for HPV DNA. Reactivity to the E6 protein was associated with the stage of disease; the antibody prevalence was 62.7% in cases with stages II-IV and 31.0% in cases with stage I (P < 0.005). HPV-16 serology and HPV polymerase chain reaction were compared as markers for invasive cervical cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Serologic response in human papillomavirus-associated invasive cervical cancer.

Human papillomavirus (HPV) transforming proteins E6 and E7 are uniformly expressed in HPV-associated cervical cancer. Our objective was to measure antibodies to HPV-16 E6 and E7 proteins in cervical cancer patients using an assay which would detect antibodies to conformational epitopes. Serum specimens obtained from two case-control studies of HPVs and cervical cancer were tested. The studies were performed in Cali, Colombia, South America and in 9 provinces of Spain. Cases consisted of women with invasive cervical cancer associated with HPV-16 or other HPV types and women with HPV-16-associated high-grade cervical intra-epithelial neoplasia (CIN-3). Controls for invasive cases and CIN-3 cases were women who had no cytologic abnormalities and who were matched for age and country of residence. Serum antibodies to HPV-16 E6 and E7 proteins were detected by radio-immunoprecipitation of in vitro translated proteins. Antibodies to the E6 and E7 protein were observed among 56% and 43%, respectively, of invasive cases and 1.7% and 4.1%, respectively, of controls. Antibodies to either protein were detected in 72% of sera from invasive cases and 5.8% of sera from controls. High antibody reactivity and antibodies to both proteins were found almost exclusively in invasive cases. The frequency of antibodies to the E6 protein and the E7 protein among CIN-3 cases did not differ significantly from the CIN-3 controls. Five women with HPV-18-associated invasive cervical cancer were negative for serum antibody to HPV-16 E6 and E7 proteins. Antibodies to HPV-16 E6 and E7 proteins appear to be partially virus-specific and disease state-specific markers of HPV-associated cervical cancer.

Antibodies, Viral↗
PubMed1993

Human papillomavirus in primary epithelial tumors of the lacrimal sac.

BACKGROUND: The lacrimal sac epithelium can give rise to benign and malignant neoplasms. Human papillomavirus (HPV) infection is known to be causal in the development of epithelial neoplasias elsewhere in the body. The authors have examined primary lacrimal sac tumors for the presence of HPV. METHODS: Nine primary lacrimal sac tumors (3 benign papillomas and 6 carcinomas) submitted to the Eye Pathology Laboratories at the Wilmer Institute between 1960 and 1991 were examined for the presence of HPV sequences by in situ hybridization and the polymerase chain reaction (PCR). RESULTS: Of the nine tumors, only six were suitable for analysis by PCR or in situ hybridization. All three papillomas were positive for HPV type 11. Three of the carcinomas were positive for HPV sequences, and one case could be further characterized as HPV type 18. CONCLUSIONS: Human papillomaviruses appear to be involved in the genesis of both benign and malignant neoplasms of the lacrimal sac epithelium. As in the genital tract, HPV type 11 is associated with benign lesions, whereas HPV type 18 is associated with malignancy.

Adult↗