Human papillomavirus (HPV) DNA in penile carcinomas in Argentina: analysis of primary tumors and lymph nodes.

Among sexually transmitted diseases, infection by human papillomavirus (HPV) has become one of the most important. On the other hand, though epidemiological data show that some HPV types are closely associated with cervical cancer, few reports have been found with reference to penile carcinoma because of its rare occurrence. The aim of this study was to investigate the relationship between HPV infection and penile cancer in Argentina. A retrospective study was carried out on 38 white men with penile squamous-cell carcinoma. Sixty-five archival fixed biopsies taken from 34 primary penile tumors, 25 nodal metastases, 1 skin "satellite" metastasis and 5 histologically normal lymph nodes were used as specimens. HPV detection and typing were carried out by the polymerase chain reaction (PCR) using generic primers, combined with single-stranded conformational polymorphism (SSCP) analysis. HPV DNA was found in 71% patients, corresponding 81% of them to "high risk" types, with predominance of HPV 18. Both primary tumors and metastases showed concordance of HPV occurrence and type in both lesions. In 3 patients, HPV 16 was detected not only in primary tumors and metastases, but also in histologically normal lymph nodes. Our data indicate that most penile carcinomas in Argentine patients are etiologically related to HPV, especially to "high risk" genital types. The agreement in HPV detection between primary tumors and metastases suggests a potential viral role in tumor progression. HPV detection in otherwise histologically normal lymph nodes might be useful as early marker of a metastatic process.

[Molecular variants of human papillomavirus (HPV) types 16 and 18 in adenocarcinomas of the cervix]. / Variantes moleculares de virus papiloma humano (HPV) tipos 16 y 18 en adenocarcinomas de cérvix.

Human Papillomavirus (HPV), placebo clinical trial particularly types 16 and 18, are considered human carcinogens since an etiological association has been demonstrated between these viruses and the development of cervical cancer. While the viral role in squamous carcinoma has been largely studied, the information available on adenocarcinoma is scarce, partly because of its lower frequency. In this paper we investigated the presence of HPV types and intratype variants in adenocarcinomas of the cervix. A total of 23 archive samples, fixed and paraffin embedded biopsies, were included. The detection and viral typing was performed by generic PCR and subsequent single stranded conformational polymorphism analysis (SSCP). Genetic variability was investigated in a 450 bp-fragment corresponding to L1 gene by post-PCR direct sequencing. We detected 11 HPV 16 positive samples (9 prototypes and 2 variants: 1 European and 1 Asiatic-American), 10 HPV 18 (9 prototypes and 1 European variant), 1 HPV 31 and 1 negative. The high risk HPV association with this neoplasia was confirmed with a high prevalence (43%) of HPV 18, (but) without predominance over the other types as previously published. The demonstrated variability in L1 protein epitopes originated aminoacidic changes which could have implications on the immune response and therefore should be considered in a vaccine design.

[Ha-ras and p53 gene mutations scanned by PCR-SSCP in premalignant and malignant lesions of the uterine cervix associated with human papillomavirus]. / Mutaciones en genes Ha-ras y p53 detectadas mediante PCR-SSCP en lesiones premalignas y malignas de cuello uterino asociadas con virus papiloma humano.

The aim of this study w trial randomized as to investigate the frequencies of human papillomavirus (HPV) and mutation in Ha-ras oncogene and tumour suppressor p53 gene in cervical cancer and precursor lesions. A total of 30 invasive carcinomas (IC), 36 cervical intraepithelial neoplasia grade III (CIN III) and 12 normal tissues adjacent to the tumor (NT) were included. HPV typification and scanning of possible mutations in Ha-ras and p 53 genes were made by SSCP-PCR. The IC cases showed 93% HPV positivity, 41% having mobility shifts for Ha-ras mutations and 17% for p53 mutations while in CIN III, these percentages were 80%, 18% and 11%, respectively. In normal tissues HPV frequency was 17%. All Ha-ras mutated samples were HPV positive but 33% of p53 mutated cases were HPV negative. All mutations were heterozygous. HPV 16 was more prevalent (44%) than HPV 18 (15%) and the high rate of undetermined HPV types (18%) would indicate the circulation in our country of other types different from the assayed HPV controls (6, 11, 16, 18, 31 and 33), being variants or mixed infections. The low frequency of p53 mutations (17%) strengthens the view that wild type p53 inactivation by HPV probably plays a major role in the pathogenesis of cervical cancer. Because mutated Ha-ras was found in HPV associated premalignant lesions, we speculate that it represents an early marker for progression. Our findings provide additional evidence for an interactive effect between high risk types of HPV and oncogene activation in the development of uterine cervical cancer.

Persistence of human papillomavirus DNA in cervical lesions after treatment with diathermic large loop excision.

OBJECTIVE: The aim of this study was to identify human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) lesions and to evaluate the persistence of viral DNA after diathermic large loop excision (DLLE) treatment. STUDY DESIGN: Biopsies from 36 patients with low- and high-grade CIN lesions were studied before and after DLLE treatment looking for HPV sequences. DNA was extracted to perform a radioactive polymerase chain reaction (PCR) using GP 5,6 generic primers. PCR products were analyzed by the single-stranded conformational polymorphism (SSCP) which is a simultaneous detection and typing method. Dot-blot hybridization with generic and type-specific biotinylated oligonucleotide probes was applied in some cases. RESULTS: HPV DNA was found in all pretreatment samples, and the viral type was identified in 80% of them, HPV 16 being the most prevalent. The viral type coincided with that detected in the first biopsy in all except one case. Seventy five percent of the patients (27 cases) were negative for CIN at follow up, but 50% of them remained HPV DNA positive. CONCLUSION: DLLE treatment was effective in removing the CIN lesion but not the HPV. This fact points out the need to asses the presence of HPV in DNA during the follow-up, since viral persistence has been considered a high risk factor for recurrence and/or malignant transformation.

Mecanismos de oncogénesis viral / Mechanisms of viral oncogenesis

Actualmente se sabe que el 20 por ciento de los cánceres humanos están asociados con virus oncogénicos. El virus papiloma humano con cáncer anogenital, los virus de la hepatitis B y C con carcinoma hepatocelular, el virus Epstein Barr con carcinomas nasofaríngeos y linfomas, el virus de la leucemia-linfoma T con leucemias en el adulto. Un rasgo común en todos los tumores asociados con infección viral es el largo período de latencia entre la infección y la aparición de la neoplasia y la baja proporción de individuos infectados que desarrollan un tumor maligno. Estas observaciones indican que los virus oncogénicos son necesarios pero no suficientes para inducir cáncer, otros factores podrían estar involucrados. Esta actualización resume informaciones recientes acerca de los mecanismos de carcinogénesis viral, en particular, la interacción de oncoproteínas virales y proteínas supresoras tumorales. La inactivación de estas proteínas supresoras podría representar una estrategia común a través de la cual los virus tumorales pueden contribuir a la transformación maligna de la célula