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K V Shah

Publications and source records attributed to K V Shah.

At least 55 records · Page 3Linked to original sources
PubMed1998

Risk factors for juvenile onset recurrent respiratory papillomatosis.

BACKGROUND: Children born to condylomatous mothers are at risk for developing juvenile onset recurrent respiratory papillomatosis (JORRP). We inquired whether the triad of vaginal delivery, being firstborn and maternal age of <20 years are also risk factors for JORRP. METHODS: Data for JORRP and adult onset recurrent respiratory papillomatosis cases were obtained from questionnaires answered by patients or their parents for the Recurrent Respiratory Papillomatosis Foundation. The observed numbers of cesarean births, first order births and births to mothers <20 years old were compared with expected numbers for the same variables, which were computed by distributing the cases by year of birth and then applying to them national annual statistics for the year of birth. In addition observed and expected numbers of first order births to mothers <20 years old were compared with corresponding numbers in mothers 20 years old or older. RESULTS: In JORRP cases the relationships be tween observed and expected numbers of cases were as follows: cesarean births, 4.6-fold less; first order births, 1.6-fold greater; maternal age <20 years old, 2.6-fold greater. All these differences were statistically highly significant. The observed parity effect was mediated to a large extent by maternal age. In contrast there were no significant differences between observed and expected numbers of adult onset recurrent respiratory papillomatosis cases with respect to any of the above variables. CONCLUSIONS: Young primiparous mothers with condylomas are at a high risk for transmission of JORRP to their infants. The option of cesarean delivery should be discussed with a mother who has condyloma at the time of delivery.

Adult↗
PubMed1998

A survey of human papillomavirus 16 antibodies in patients with epithelial cancers.

Human papillomavirus (HPV), particularly HPV 16, is linked to the development of cervical cancer. However, the role of HPV 16 in a number of extra-cervical epithelial tumours is controversial. To assess exposure to HPV 16 in patients with different cancers, we conducted a large serosurvey of 905 patients with 21 types of tumours and measured IgG to HPV 16 virus-like particles (VLPs) using a well characterized enzyme linked immunosorbent assay (ELISA). Patients with cervical cancer were considered 'positive controls', as about half were expected to be specifically HPV 16-related. A non-cancer study group consisting of 48 patients with endocrine disorders (eg diabetes) was also tested. HPV 16 antibody prevalence was highest in patients with cancers of the cervix (52% +/- 7%), vulva (27% +/- 9%), vagina (27% +/- 13%) and penis (63% +/- 16%). Seroprevalence was much lower in the non-cancer group (4% +/- 3%) and all other cancer patients: uterus (9% +/- 4%); ovary (4% +/- 3%); testis (5% +/- 4%); prostate (6% +/- 4%); squamous carcinoma (6% +/- 3%) and adenocarcinoma (4% +/- 3%) of the lung; rectum (2% +/- 2%); pancreas (8% +/- 4%); colon (2% +/- 2%); stomach (0%); oesophagus (8% +/- 4%); buccal cavity (12% +/- 5%); breast (10% +/- 4%); non-melanomatous (9% +/- 6%) and melanomatous (6% +/- 3%) skin tumours; bladder (8% +/- 4%); and kidney (2% +/- 2%). The results confirm the strong relation of HPV with several lower anogenital tract tumours, but, at least in this population, fail to identify additional epithelial tumours associated with high seroprevalence of HPV 16 VLP antibodies.

Adult↗
PubMed1998

Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7.

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.

Adult↗
PubMed1997

Correlation between the presence of anti HPV33 VLP antibodies and HPV DNA in cervical neoplasia patients.

The L1 capsid proteins derived from human papillomavirus (HPV) type 33 were expressed in a recombinant baculovirus system using Sf9 insect cells. Selected sera originating in women from case-control study carried out in Spain and Colombia found negative and positive for HPV16, 18, 31, 33 and 35 DNA were tested in ELISA for the presence of IgG antibodies to purified virus-like particles (VLP). The reactivity was type-restricted with the possible exception of HPV31.

Antibodies, Viral↗
PubMed1997

Prevalence of penile human papillomavirus DNA in husbands of women with and without cervical neoplasia: a study in Spain and Colombia.

To investigate the role of men in cervical cancer, 816 husbands of women enrolled in four case-control studies of cervical neoplasia in populations at high (Colombia) and low (Spain) risk for cervical cancer were interviewed. Exfoliated cells from the penis were obtained and analyzed by polymerase chain reaction for the presence of human papillomavirus (HPV) DNA. Penile HPV DNA prevalences were higher in husbands of women with cervical neoplasia than in husbands of controls. Husbands of controls in Colombia had a 5-fold higher penile HPV DNA prevalence than the corresponding husbands in Spain. Strong dose-response relationships were found between penile HPV DNA prevalence and all sexual behavior-related variables in Spain but not in Colombia. Sexual promiscuity is the most important risk factor for penile HPV infections. Differences in HPV DNA prevalence in the male populations of Spain and Colombia are consistent with their 8-fold difference in cervical cancer incidences.

Adult↗
PubMed1997

Investigation of human urine for genomic sequences of the primate polyomaviruses simian virus 40, BK virus, and JC virus.

Recent reports of the detection of simian virus 40 (SV40) nucleotide sequences in ependymomas, choroid plexus tumors, osteosarcomas, and mesotheliomas have raised the possibility that SV40, which naturally infects Asian macaques, is circulating among humans. This possibility was examined by performing polymerase chain reaction assays on urine samples of 166 homosexual men, 88 of them human immunodeficiency virus (HIV)-seropositive, for genomic sequences of SV40 as well as of human polyomaviruses BK virus (BKV) and JC virus (JCV). Tests with masked urine specimens spiked with SV40-transformed cells were included to monitor the SV40 assay. SV40, BKV, and JCV sequences were identified, respectively, in 0, 14%, and 34% of the urine specimens. JCV viruria was far more common (37%) than BKV viruria (5%) in HIV-seronegative persons. HIV infection and more severe immunosuppression were associated with a higher frequency of BKV viruria. In summary, SV40 viruria was not detected among homosexual men who shed human polyomaviruses at a high frequency.

AIDS-Related Opportunistic Infections↗
PubMed1997

Prevalence of antibodies to human papillomavirus (HPV) type 16 virus-like particles in relation to cervical HPV infection among college women.

A human papillomavirus type 16 (HPV-16) virus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA) was used to measure serum antibody to capsid proteins in 376 sexually active college women who were also screened for the presence of genital HPVs by PCR and interviewed for demographic and behavioral risk factors for HPV infection. The seroprevalence was 46% in women with HPV-16 DNA in the genital tract. The corresponding values for women who harbored other HPV types or no HPV in the genital tract were 30 and 19%, respectively (HPV-16 group versus no-HPV group; odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5 to 8.9). The antibody response was significantly higher among women with a high viral load than among those with a low viral load (median optical density value, 0.838 versus 0.137, P = 0.009). Comparable levels of seroreactivity were observed among women infected with HPV types distantly or closely related genetically to HPV-16. Seroreactivity was significantly associated with an age of 25 to 30 years (OR, 2.3; 95% CI, 1.2 to 4.4), three or more lifetime sexual partners (OR, 2.9; 95% CI, 1.1 to 10), and history of a sexually transmitted disease other than HPV (OR, 3.1; 95% CI, 1.5 to 6.3). The percent seropositivity increased linearly with number of lifetime sexual partners until reaching a plateau at 35% for women with more than six partners (chi for linear trend, P < 0.001). The low sensitivity of HPV-16 VLP-based ELISA may limit the usefulness of the assay as a diagnostic test for HPV-16 infection. However, the assay appears to have adequate specificity and should be useful as an epidemiological marker of HPV-16 infection and sexual behavior.

Adolescent↗
PubMed1997

Comparison of PCR and hybrid capture methods for detection of human papillomavirus in injection drug-using women at high risk of human immunodeficiency virus infection.

We compared Hybrid Capture, a new technique for detection of human papillomaviruses (HPV), with a PCR assay based on L1 consensus primers. By both methods, the HPV prevalence was higher in human immunodeficiency virus (HIV)-positive women than in HIV-negative women. PCR had a higher sensitivity (0.89 versus 0.48) but lower specificity (0.43 versus 0.93) for detection of Pap smear abnormalities, compared to Hybrid Capture. The higher intensity of hybridization signal by PCR was related to higher estimates of viral load by Hybrid Capture.

DNA, Viral↗
PubMed1997

Interlaboratory agreement among results of human papillomavirus type 16 enzyme-linked immunosorbent assays.

Serological assays for measuring antibodies to human papillomavirus type 16 (HPV-16) virus-like particles (VLPs) have become important epidemiologic tools in recent years. However, the interlaboratory replicability of these assays has not been assessed. In this investigation, three laboratories tested a panel of specimens obtained from two different groups: 265 subjects in a vulvar cancer case-control study and 107 healthy volunteer blood donors. Each laboratory used an enzyme-linked immunosorbent assay (ELISA), but no attempt was made to standardize assay procedures among the three laboratories. The data showed good day-to-day intralaboratory replicability in laboratory 1 (correlation coefficient, > or = 0.88) and good intra-assay variability in laboratory 3 (correlation coefficient, > or = 0.93). Interlaboratory correlations, likewise, ranged between 0.61 and 0.80 in both case-control study subjects and healthy blood donors, indicating that ELISA optical density (OD) values between laboratories were linearly related regardless of the population. Kappa coefficients (kappa), based on each laboratory's categorical interpretation of its results (as positive or negative), showed good agreement (kappa, > 0.6) in case-control study subjects and moderate agreement (kappa, > or = 0.4) in blood donors, a population that had few strongly positive sera. When OD values near seropositive cutoffs were treated as indeterminates, there was little discordance between laboratories in either population. The data suggest that each laboratory measured the same humoral immune response and that their HPV-16 VLP ELISAs performed similarly (Pearson correlations). Interlaboratory differences, however, probably due to reagents and procedures, were considerably greater than intralaboratory day-to-day variability. Interlaboratory agreement in determining seropositivity (kappa) could be improved by sharing positive and negative serum controls and by treating marginal results as indeterminate. As part of continuing cooperation to improve interlaboratory agreement, we are preparing bulk serum control specimens to be shared and made available to interested researchers.

Enzyme-Linked Immunosorbent Assay↗
PubMed1997

Human papillomavirus DNA and antibodies to human papillomaviruses 16 E2, L2, and E7 peptides as predictors of survival in patients with squamous cell cervical cancer.

PURPOSE: To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antibodies to selected HPV 16 peptides are predictors of tumor recurrence and long-term survival in patients with squamous cell invasive cervical cancer. SUBJECTS AND METHODS: Four hundred seventy-one cases included in two population-based case-control studies underwent follow-up evaluation. The survival and cause of death were ascertained for 410 cases (87%), with a median follow-up time of 4.6 years after diagnosis. HPV DNA was assessed using an L1 polymerase chain reaction (PCR)-based system and Southern hybridization (SH) on scraped cytologic specimens or biopsies. HPV 16 antibodies to E2, L2, and E7 peptides were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: Clinical stage was the only independent prognostic factor for recurrence or survival. Although seropositivity to HPV 16 E7/3 peptide predicted a twofold excess risk of mortality (adjusted hazards ratio [HRa] = 2.0; 95% confidence interval [CI], 1.2 to 3.3), the association was restricted to stage I (HRa = 6.6; 95% CI, 1.2 to 37.6) and II (HRa = 5.9; 95% CI, 2.1 to 16.5) patients. The presence of HPV DNA (HRa = 0.9; 95% CI, 0.5 to 1.5), different estimates of the HPV viral load and the HPV type identified were not predictors of tumor recurrence or survival. CONCLUSION: The presence of antibodies to HPV 16 E7 proteins is of prognostic value in early-stage cervical cancer. Our results provide strong evidence that detection and typing of HPV DNA in cervical cells or tissues is not a prognostic factor for recurrence or survival.

Adult↗
PubMed1997

Antibodies to human papillomavirus 16 and subsequent in situ or invasive cancer of the cervix.

Our objective was to examine whether past infection with human papillomavirus (HPV)-16, as determined by an antibody assay, is a risk factor for subsequent cervical cancer. Incident cases of in situ or invasive cervical cancer occurring between 1975 and 1990 in a cohort of over 11,000 healthy women in Washington County, MD, were identified. The baseline sera of cases and of matched controls, collected in 1974, were examined for IgG antibodies reactive with virus-like particles of HPV-16, a cancer-associated HPV, and HPV-6, a low-risk HPV. Postdiagnosis sera of 11 cases were also assessed similarly. Fourteen cases of invasive and 28 cases of in situ cervical cancer and 83 matched controls were evaluated. The main outcome measure was the risk of cervical cancer in women who had HPV-16 or HPV-6 antibodies in prediagnostic sera. Antibodies to HPV-16 but not to HPV-6 were a marker for subsequent occurrence of cervical cancer. Case sera were reactive more often and more strongly with HPV-16 virus-like particles than were sera of matched controls. The presence of antibodies to HPV-16 was significantly associated with an increased risk of cervical cancer (odds ratio, 3.9; 95% confidence limits, 1.4, 10.7); high antibody levels to HPV-16 were associated with an even greater risk of cervical cancer (odds ratio = 7.5, 95% confidence limits 1.5, 36.3). The association with cervical cancer was strengthened after adjustment for smoking and years of education. In tests of 11 pairs of pre- and postdiagnostic sera, HPV-16 antibodies did not decline markedly over a 7-13-year time period, and seroconversion to HPV-16 appeared to have occurred in 2 cases. The serological data indicate that HPV-16 infection is associated with future risk of cervical cancer and strengthen the evidence for the etiological role of HPVs in cervical cancer.

Adult↗
PubMed1996

Male sexual behavior and human papillomavirus DNA: key risk factors for cervical cancer in Spain.

BACKGROUND: It is now established that certain types of human papillomaviruses (HPVs) are the sexually transmitted agents etiologically linked to cervical cancer. Studies assessing the contribution of the male's sexual behavior and genital HPV DNA status to the risk of development of cervical neoplasia in sexual partners have yielded inconsistent results. PURPOSE: This study evaluates the role of men's sexual behavior and the presence of HPV DNA in the penis on the development of cervical cancer in their sexual partners in Spain, a low-risk area for cervical neoplasia. METHODS: Husbands (n = 633) of women participating in two case-control studies of cervical neoplasia were interviewed to obtain information on lifestyle habits, including sexual practices. Cytologic samples were taken from the distal urethra and the surface of the glans penis of 183 husbands of case women and of 171 husbands of control women. These samples were analyzed by a polymerase chain reaction-based system using a generic probe and 25 type-specific probes for the detection and typing of HPV DNA. Serologic specimens were also obtained and analyzed for antibodies to Chlamydia trachomatis, Treponema pallidum, herpes simplex virus type II, and Neisseria gonorrhoeae. RESULTS: The presence of HPV DNA in the husbands' penis conveyed a fivefold risk of cervical cancer to their wives (adjusted odds ratio [OR] for HPV DNA positivity = 4.9; 95% confidence interval [CI] = 1.9-12.6). The risk of cervical cancer was strongly related to HPV type (adjusted OR for HPV type 16 = 9.0; 95% CI = 1.1-77.5), to the husbands' number of extramarital partners (adjusted OR = 11.0; 95% CI = 3.0-40.0; for > or = 21 women versus one), and to the number of prostitutes as extramarital sexual partners (adjusted OR = 8.0; 95% CI = 2.9-22.2; for > or = 10 women versus none). Presence of antibodies to C. trachomatis (adjusted OR = 2.6; 95% CI = 1.4-4.6) and an early age at first sexual intercourse of the husband (adjusted OR = 3.2; 95% CI = 1.7-5.9; for < or = 15 years versus > or = 21 years) were also associated with cervical neoplasia in the wife. After adjustment for these variables and for the wife's pack-years of smoking, the husband's smoking was moderately associated with cervical cancer in his wife (adjusted OR = 2.5; 95% CI = 1.4-4.4; for > or = 26.2 pack-years versus none). CONCLUSIONS: The study supports the role of men as vectors of the HPV types that are related to cervical cancer. Life-time number of female sexual partners, number of female prostitutes as sexual partners, and detection of HPV DNA in the penis of husbands are all surrogate markers of exposure to HPV during marriage. IMPLICATIONS: Men who report multiple sexual partners or who are carriers of HPV DNA may be vectors of high-risk HPV types and may place their wives at high risk of developing cervical cancer. Prostitutes are an important reservoir of high-risk HPVs.

Carcinoma, Squamous Cell↗
PubMed1996

Difficulty in elucidating the male role in cervical cancer in Colombia, a high-risk area for the disease.

BACKGROUND: Epidemiologic evidence has been inconclusive in linking men's sexual behavior and genital human papillomaviruses (HPVs) with cervical cancer risk in their sexual partners in areas with a high incidence of cervical cancer. PURPOSE: This study assesses the role of men's sexual behavior and the presence of penile HPV DNA on the risk of their wives' developing cervical neoplasia in an area in Colombia with a high incidence of cervical cancer. METHODS: A total of 210 husbands of women with cervical intraepithelial neoplasia grade III (n = 118) or invasive squamous cell carcinoma of the cervix (n = 92) and a total of 262 husbands of women recruited as control subjects (173 and 89, respectively) were interviewed. Questionnaires included detailed information on sexual behavior. Exfoliated cells were obtained from the glans penis and from the distal urethra of the penis. The specimens were analyzed for HPV DNA by use of a polymerase chain reaction-based assay that included a generic probe and 25 type-specific probes. Serum specimens were collected and analyzed for antibodies to Chlamydia trachomatis, Treponema pallidum, herpes simplex virus type II, and Neisseria gonorrhoeae. RESULTS: Limited education (adjusted odds ratio [OR] = 4.4; 95% confidence interval [CI] = 1.9-9.8; for no schooling versus secondary or higher education) and presence of antibodies to C. trachomatis (adjusted OR = 2.5; 95% CI = 1.5-4.4) in husbands were the only identified risk factors for cervical neoplasia in their wives. The prevalence of HPV DNA in the penis was 25.7% among husbands of case women and 18.9% among husbands of control women (adjusted OR = 1.2; 95% CI = 0.6-2.3). Neither the lifetime number of female sexual partners (adjusted OR = 1.0; 95% CI = 0.4-2.6; for > 50 partners versus one to five) nor the lifetime number of female prostitutes as sexual partners (adjusted OR = 1.2; 95% CI = 0.7-2.0; for > or = 21 prostitutes versus one to five) was associated with the risk of cervical cancer. CONCLUSIONS: Our results are compatible with the hypothesis that in the population of Cali, whose women are at high risk of developing cervical cancer, exposure to HPV among young men is a common occurrence and is mediated by contacts with large numbers of female sexual partners and prostitutes. These widespread sexual practices limit the power of case-control studies to detect significant associations between men's sexual behavior and the cervical cancer risk in their sexual partners. HPV DNA detection in the penis of adult men is a poor reflection of lifetime exposure or of etiologically relevant exposure to HPV. The role of C. trachomatis in cervical carcinogenesis deserves further investigation. IMPLICATIONS: Further research is needed to elucidate the male's role in cervical carcinogenesis in populations at high risk for cervical cancer. HPV DNA prevalence surveys and studies of the natural history of HPV in young men will be of great value.

Carcinoma, Squamous Cell↗
PubMed1996

Serological response to HPV16 in CIN-III and cervical cancer patients. Case-control studies in Spain and Colombia.

This study evaluates the association of antibodies against HPV-16-derived peptides with cervical cancer and estimates the sensitivity and specificity of the serological assays in relation to HPV DNA detection in cervical cells by PCR. Study subjects were derived from 4 case-control studies carried out in Spain and Colombia. Sera from 544 cases of CIN III and invasive cancer and of 543 age-matched controls were tested for antibodies to 5 peptides derived from E2, E7 (3 partially overlapping frames of HPV 16 denoted E7/ 1, E7/2, E7/3) and L2 open reading frames of HPV 16. HPV DNA was detected using a L1-PCR based method. Among cancer controls, antibody response to E2 and E7/1, E7/2, E7/3 was higher in Colombia (22.5%,7.2%,11.7%,12.6% respectively) than in Spain (17.1 %, 4.7%, 5.9%, 5.9%). E7 antibodies were related to stage, particularly in CIN III vs. invasive stages and less markedly within invasive stages. Detection of antibodies to the E7/1 was associated to CIN III (OR = 1.8). The risk of invasive cervical cancer was increased among those with antibodies to E2 (OR = 2.2), to E7/1 (OR = 4.2), to E7/2 (OR = 4.3), and to E7/3 (OR = 2.5). Presence of antibodies to all the 3 E7 peptides increased the risk of CIN III (OR = 5.6) and that of invasive cancer (OR = 17.5). High levels of antibodies to E7/1 or E7/2 or E7/3 increased the risk of invasive cervical cancer (OR for high levels of antibodies vs. negatives to E7/1 OR = 22.6; E7/2 OR = 7.5, E7/3 OR = 3.4). In the present analysis, antibodies to L2 were not associated with either CIN III or cervical cancer. Serological markers of HPV 16 detected less than half of the HPV-16-DNA-positive cases. It is concluded that antibodies to E2 and particularly E7 antigens are strongly associated with cervical cancer. Antibodies to E7 seem to be a moderate marker of tumor burden.

Adult↗
PubMed1996

Human papillomavirus DNA detection in cervical specimens by hybrid capture: correlation with cytologic and histologic diagnoses of squamous intraepithelial lesions of the cervix.

Human papillomavirus (HPV) DNA detection in cervical specimens was correlated with cytologic and histologic diagnoses for 151 women who were referred to the Johns Hopkins Hospital colposcopy clinic for evaluation of an abnormal Pap smear. HPVs were identified as "high-risk" or "low-risk" by Hybrid Capture. The final disease status was categorized as high-grade squamous intraepithelial lesion (HSIL) by histology (n = 26), low-grade squamous intra-epithelial lesion (LSIL) by histology (n = 43), equivocal [histology negative, cytology atypical squamous cells of undetermined significance (ASCUS) or higher, n = 42], and negative (both histology and cytology negative, n = 40). Thirty-five percent of disease-negative women and 84% of the women with biopsy-proven or equivocal disease were HPV-positive. Ninety-two percent of the HPV-positive women harbored high-risk HPVs, either high-risk HPVs alone (77%) or high-risk HPVs along with low-risk HPVs (15%). High-risk HPVs predominated in disease-negative as well as disease-positive women. Collection of specimens with a cytobrush was more efficient for HPV DNA detection than collection by cervicovaginal lavage. Large amounts of HPV DNA correlated with presence of HSIL or LSIL. For detection of HSIL, considering only brush samples, the sensitivities of abnormal cytology (ASCUS or higher), of high-risk HPVs, and of the two combined were, respectively, 87, 93, and 100%; the corresponding specificities were 30, 30, and 20%. HPV DNA detection may be most beneficial in populations with low HPV prevalence.

Adult↗