Human papillomavirus infection in Honduran women with normal cytology.

OBJECTIVE: This study was aimed at estimating type-specific HPV prevalence and its cofactors among Honduran women with normal cytology in order to provide valuable information to health policymakers about the epidemiology of this important sexually transmitted infection. METHODS: A total of 591 women with normal cytology from Tegucigalpa, Honduras were interviewed and tested for HPV using the SPF10 LiPA25. A structured epidemiological questionnaire was administered to each woman. RESULTS: The overall HPV prevalence was 51%. Twenty-three types of HPV were detected; HPV 16, 51, 31, 18, and 11 were the most common. The highest prevalence of cancer associated HPV types (15.0%) was found in the women less than 35 years. Besides the association with age, the main independent predictors of HPV infection were the lifetime number of sexual partners and having a low socioeconomic status and less than 5 previous Pap smears. CONCLUSIONS: In the population studied, there was a broad diversity of HPV infections, with high-risk types being the most common types detected. The establishment of a well-characterized population with regard to the community prevalence of type-specific HPV infection will provide a valuable baseline for monitoring population effectiveness of an HPV vaccine.

Co-factors related to the causal relationship between human papillomavirus and invasive cervical cancer in Honduras.

BACKGROUND: A case-control study was conducted in Honduras to identify co-factors in the carcinogenic pathway by which human papillomavirus (HPV) causes invasive cervical cancer. METHODS: Ninety-nine cases aged 23-65 (median 47) years participated. Two controls were matched to each case by age and clinic where they first presented for cytological screening; controls had no cervical abnormalities. Information on risk factors was obtained by personal interviews in the clinics regarding sociodemographic, reproductive and behavioral characteristics. Human papillomavirus was detected in cervical scrapes by general primer-mediated polymerase chain reaction (PCR) followed by sequence analysis to identify the different types present. RESULTS: All cases had squamous cell tumours and most were FIGO (International Federation of Gynecologists and Obstetricians) class II or higher; HPV was strongly associated with cervical cancer (odds ratio [OR] = 7.66, 95% CI : 3.88-15.1). Among HPV-positive women, dose-response relationships were observed for education, age at first intercourse and exposure to wood smoke that persisted after adjustment for previous screening. Among HPV-negative women, the number of sexual partners and parity were associated with cervical cancer. The protective effect of previous cytological screening operated independently of HPV. CONCLUSIONS: Our findings speak for the powerful role that both primary and secondary education plays in fostering a lifestyle that reduces the risk of invasive cervical cancer. The data suggest that important elements of such a lifestyle include later age at first sexual intercourse, a limited number of pregnancies, greater likelihood of undergoing cytological screening and reduced exposure to carcinogens in the household environment.

Human papillomavirus infection, cervical dysplasia and invasive cervical cancer in Honduras: a case-control study.

A substantial body of evidence has confirmed human papillomavirus (HPV) infection as the central etiological agent in human cervical carcinogenesis. In Honduras, cervical cancer is the most common cancer among women, with a high annual incidence. We conducted a population-based, case-control study of 229 patients with different grades of CIN and invasive cervical cancer and 438 matched controls. A structured questionnaire was used to investigate known and probable risk factors for cervical cancer. Cervical scrapes were tested for the presence of different HPV types using a general primer-mediated PCR followed by PCR-based sequencing. HPV DNA was detected in 87% of all cancer in situ and invasive cancer cases, and 95% of invasive cases could be attributed to high-risk types. In control women, 39% were positive for HPV DNA sequences. HPV 16 prevalence ranked highest in all stages of cervical dysplasias, invasive cancers and controls. A statistically significant association with HPV was observed for CIN II, CIN III and invasive cancer, showing an upward trend to more severe lesions and being more pronounced for HPV 16 and related types. The OR for HPV 16- and 18-related invasive cancer cases was 14.88 (95% CI 5.12-43.25) and 74.66 (95% CI 7.77-717.62), respectively. Our results confirm a central role of HPV as the cause of cervical cancer in Honduras and provide information as to the type distribution of HPVs in the country.

HLA DOA1 and DOB1 loci in Honduran women with cervical dysplasia and invasive cervical carcinoma and their relationship to human papillomavirus infection.

Molecular and epidemiological studies have demonstrated that certain types of human papillomavirus (HPV), mainly HPV-16 and HPV-18, are the primary causes of cervical cancer and its precursor lesions; there is now evidence for a clear association with specific HLA class I and class II loci contributing independently to the expression of cervical cancer. Among Honduran women carcinoma of the cervix is the most common type of cancer, and infections with high-risk HPV types are highly prevalent. To study the interactive role of viral-host genetics, we performed PCR amplification of DNA and sequence-specific oligonucleotide probe typing on cervical scrapes from 49 women [24 with cervical intraepithelial neoplasia stage III or cervical cancer (severe cases) and 25 with stage I or II cervical intraepithelial neoplasia (mild cases)] and 75 control subjects to look for possible associations between HPV and HLA class II DQA1 and DQB1 alleles in the development of dysplasias and invasive cancer. This analysis revealed a predominance of HLA-DQA1*0301 among severe-case patients [relative risk (RR) = 3.45, p = 0.008), whereas DQA1*0501 was negatively associated (RR = 0.30, p = 0.03), suggesting a protective effect of this allele. HPV typing showed a decreased relative risk among the HPV-16 or HPV-18 carrying patients and other HPV-related positive patients in the presence of DQB1*0602 compared with positive control subjects (p = 0.04). No statistically significant allele frequency difference was observed between mild dysplasia cases and control subjects. The results suggest that DQA1*03011, which is in linkage desequilibrium with all HLA-DR4 alleles, confers an increased risk for severe cervical dysplasia and invasive cancer, whereas DQA1*0501, which is in several DR52 haplotypes, has a protective effect. Furthermore, specific HLA-DQB1 sequences may be important in determining the immune response to HPV peptides and may affect the risk for cervical cancer after HPV infection in mestizo Honduran women.

Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)-retinamide in human breast cancer cell lines.

The potent mitogenic activity of insulin-like growth factor I (IGF-I) on breast epithelium is inhibited by retinoic acid in oestrogen receptor-positive (ER+) breast cancer cell lines. We studied and compared the effects of N-(4-hydroxyphenyl)-retinamide (4-HPR) in terms of growth inhibition and modulation of the IGF-I system in ER+ (MCF-7) and oestrogen receptor-negative (ER-) (MDA-MB231) breast cancer cell lines. Treatment with 1-10 microM 4-HPR for up to 96 h induced a dose- and time-dependent inhibition of proliferation in both breast cancer cell lines. Induction of apoptosis was much more evident in MCF-7 than in MDA-MB231 cells (30-40% compared with 0-5% respectively at 5 microM for 48 h). Exogenous human recombinant IGF-I (hr-IGF-I)-stimulated cell proliferation was abolished by 1 microM 4-HPR in MCF-7 cells. Immunoreactive IGF-I-like protein concentration in conditioned medium was reduced by 38% in MCF-7 and by 90% in MDA-MB231 cell lines following treatment for 48 h with 5 microM 4-HPR. Western ligand blot analysis showed a reduction of IGF-binding protein 4 (BP4) and BP5 by 67% and 87%, respectively, in MCF-7, whereas IGF-BP4 and -BP1 were reduced by approximately 20% in MDA-MB231 cells. Exposure to 5 microM 4-HPR for 48 h inhibited [125I]IGF-I binding and Scatchard analysis revealed a decrease of more than 50% in maximum binding capacity (Bmax) and a reduced receptor number/cell in both cancer cell lines. Steady-state type I IGF-receptor mRNA levels were reduced by approximately 30% in both tumour cell lines. We conclude that 4-HPR induces a significant down-regulation of the IGF-I system in both ER+ (MCF-7) and ER- (MDA-MB231) breast cancer cell lines. These findings suggest that, in our model, interference with the ER signalling pathway is not the only mechanism of breast cancer growth inhibition by 4-HPR.

A sero-epidemiological study of the relationship between sexually transmitted agents and cervical cancer in Honduras.

To investigate a possible cause-and-effect relationship between sexually transmitted diseases and cervical cancer, we performed a sero-epidemiological study on the presence of antibodies against a number of sexually transmitted agents (STAs) in patients with cervical cancer and their matched controls. In this study, we used serological techniques to investigate the presence of antibodies to cytomegalovirus, herpes simplex virus type 2, human immunodeficiency virus, Chlamydia trachomatis, Treponema pallidum and human papillomavirus (HPV) early protein E7 in sera from patients with cervical cancer, cervical intra-epithelial neoplasia and individually matched, healthy controls. The presence of antibodies to infectious agents other than HPV appeared not to be associated with risk of cervical neoplasia in either univariate or multivariate analysis. After adjustment for cytology, schooling and presence of HPV DNA in cervical scrapes, there was a significantly higher prevalence of antibodies to HPV-16 E7 protein in sera from patients with cervical cancer (OR = 3.6, 95% CI 1.0-12.9) than in healthy controls. The highest antibody prevalence was found among HPV-16 DNA-positive cervical cancer patients (33%). Our results indicate that in these study groups past infections with the STA considered seems to be of no apparent relevance for cervical carcinogenesis and that the HPV-16 anti-E7 response appears to be associated with cervical cancer.

Association of infections with human immunodeficiency virus and human papillomavirus in Honduras.

The etiologic role of the oncogenic types of human papillomavirus (HPV) in the development of cervical cancer has been widely proven. Since this cancer occurs more frequently in immunosuppressed individuals, we sought to evaluate the prevalence of HPV infection among human immunodeficiency virus (HIV)-infected and HIV-noninfected prostitutes in Tegucigalpa, Honduras. Cervical scrapes were collected from 23 HIV-seropositive and 28 HIV-seronegative prostitutes for HPV DNA detection by the polymerase chain reaction. Fifty-six percent of the HIV-seropositive women and only 18% of the seronegative women were HPV DNA positive (odds ratio = 6.0). In addition, there was a significant association between seropositivity for HIV with a history of sexually transmitted diseases (P < 0.01). Our data confirm the association between infections with HIV and HPV.

PIP: Numerous studies have revealed a higher prevalence of human papillomavirus (HPV)--etiologically linked to the development of cervical cancer--in women infected with HIV. This study investigated the association of HPV and HIV among 51 prostitutes in Tegucigalpa, Honduras. 23 were HIV-positive. All participants were in their early thirties, had had at least one pregnancy, and experienced their first pregnancy at a mean age of 16 years. Polymerase chain reaction identified HPV DNA in cervical scrapes from 13 (56.5%) HIV-positive women compared with only 5 (18%) HIV-negative prostitutes (odds ratio, 6.0; 95% confidence interval, 1.5-26.7). In addition, there was a significant association between HIV and a history of other sexually transmitted diseases (p 0.01). Since the progression to invasive cervical disease is more aggressive in HIV-infected women, prostitutes and other women at risk of both these infections should receive frequent cytologic screening and counseling.

Anti-insulin-like growth factor-I activity of a novel polysulphonated distamycin A derivative in human lung cancer cell lines.

1. The purpose of this study was to investigate the antiproliferative effect and the modulation of the mitogenic insulin-like growth factor-I (IGF-I) system by FCE 26644 and FCE 27784, two polyanionic sulphonated distamycin A derivative compounds, on two human non-small cell lung cancer (N-SCLC) cell lines. 2. For cell growth studies the colorimetric MTT and the thymidine incorporation assays were performed; the presence of IGF-I and IGF-binding proteins in conditioned media was revealed by radioimmunoassay and Western ligand blot, respectively. Variations at the IGF-I-receptor level were tested by binding studies on cell monolayers. 3. A significant concentration- and time-dependent cytostatic activity of FCE 26644 (IC50 approximately 200 micrograms ml-1 at 72 h) compared to its analogue FCE 27784 (IC50 > 800 micrograms ml-1) was observed in both cell lines studied. The IGF-I-stimulated proliferation of the IGF-I-responsive A549 cell line was abolished by 24 h of FCE 26644 treatment whereas FCE 27784 was inactive. FCE 26644 increased (4 to 6 fold) the secretion of IGF-I-like material and reduced the IGF-I binding (IC50 > 100 micrograms ml-1) in both A549 and Ca-Lu-1 cell lines. FCE 26644 (100 micrograms ml-1) did not affect the KD (approximately 0.5 nM) but reduced the Bmax and the number of receptor sites (50%). 4. Our findings demonstrate that the ability to down-regulate the cell proliferation of N-SCLC cell lines, shown by FCE 26644, depends at least partially, on interference with the "IGF-I mitogenic system'.

Comparison between novel steroid-like and conventional nonsteroidal antioestrogens in inhibiting oestradiol- and IGF-I-induced proliferation of human breast cancer-derived cells.

1. This study has two specific aims: (a) to compare the antioestrogenic activity of two steroidal analogues of 17 beta-oestradiol, the 7 alpha-alkylamide, ICI 164,384 and the 7 alpha-alkylsulphinylamide, ICI 182,780, with that of the triphenylethylene-derived compound 4OH-tamoxifen on a pool of human breast cancer cell lines (HBCCL) with a range of hormonal responsiveness and acquired anti-oestrogen resistance and (b) to investigate the ability of such antioestrogens to modulate the potent breast carcinoma growth-stimulatory activity of the 'IGF-I system'. 2. For the chemosensitivity investigations we used a long-term colorimetric and the short-term thymidine incorporation assay; we analysed IGF-I in conditioned media by a radioimmunoassay, IGF-I mRNA in the cells by RT-PCR and molecular species of IGF-I-binding proteins, secreted in conditioned media, by Western ligand blot. IGF-I receptors were assayed on cell monolayers by binding studies and by Scatchard analysis, we calculated KD, Bmax and sites/cell. 3. Our results indicate that ICI 182,780 and ICI 164,384 are 1.5-5.5 fold more potent than 4OH-tamoxifen in inhibiting the basal proliferation of oestrogen-receptor positive (ER+) breast cancer cell lines. Moreover we demonstrate the capacity of ICI 182,780 and ICI 164,384 to reduce, in a time-dependent fashion, oestrogen- and/or IGF-I-stimulated growth of ER+cell lines, possibly by negatively interfering with an IGF-I-like material secretion and IGF-I-receptor number. 4. Our data provide the first evidence that, on ER+human breast carcinoma cell lines, steroidal antioestrogens inhibit cell growth and modulate the IGF-I mitogenic system. The mechanism of this latter effect has yet to be identified.

Human papillomavirus and cervical cancer in Honduran women.

In this study, the relationship between human papillomavirus (HPV) infections and cervical cancer in women from Honduras was investigated. Fifteen biopsy samples, obtained from women with cervical cancer or carcinoma in situ, were embedded in paraffin and investigated for the presence of HPV. One 5-microns section was directly processed in lysis buffer and treated with proteinase K. The samples were first screened with an HPV general primer polymerase chain reaction PCR (GP-PCR) assay directed against the highly conserved L1 open reading frame of HPV. The HPV-positive biopsy specimens were rescreened with an HPV 6/11, 16, 18, 31, and 33 type-specific PCR assay. All four carcinoma in situ samples and 10 of 11 carcinomas were found to be positive for HPV. Of the carcinoma in situ samples, two contained HPV 16 DNA, one sample contained HPV 18 DNA, and one sample both HPV 16 and HPV 18 DNA. Of the carcinomas, three specimens contained HPV 16 DNA, two samples contained HPV 18 DNA, two carcinomas were positive for both HPV 16 and 18 DNA, one sample contained HPV 6/11 DNA, and two specimens were HPV positive in the GP-PCR assay but HPV negative in the type-specific PCR assays. This indicated the presence of an HPV type different from HPV 6, 11, 16, 18, 31, or 33. In one carcinoma, no HPV DNA was detected. These data suggest a close association between infection with HPV 16 and HPV 18 and cervical cancer in Honduras.