HPV Sexually Transmitted Disease - Threat For Cancer

Sobhani I, Walker F, Roudot-Thoraval F, Abramowitz L, Johanet H, Henin D, Delchier JC, Soule JC. FAMA de Colo-Proctologie et INSERM U.410, Hopital Bichat-Claude Bernard, Paris, France. iradj.sobhani@hmn.ap-hop-paris.fr

INTRODUCTION: Human papilloma virus (HPV) causes anal condyloma that is a risk factor for anal carcinoma. The incidence and mechanism of invasive anal carcinoma in patients with anal condyloma are prospectively determined. PATIENTS AND METHODS: From 1993 to 2002, 228 consecutive patients (164 HIV positive) with anal canal condylomas were included in the study, after curing of their lesions. They were asked to attend follow-up visits at 3- or 6-month intervals. We checked for anal co-infection with syphilis, gonococci, viruses (Epstein-Barr virus, cytomegalovirus, herpes simplex, HPV types), and quantified Langerhans' cells (LC) in anal mucosa at baseline and during follow up. We cured and analysed relapsed condylomas during follow up (3-112 months; median 26). Serum HIV loads and CD4 T-lymphocyte counts were determined at each visit and the densities of LC in consecutive specimens from patients with cancers were compared with that for a matched control group (n = 23). RESULTS: Analysis of 199 patients showed high-grade dysplasia (HGD) in 13.6% of patients, more in HIV-positive (16%) than in HIV-negative (6%) patients at baseline. During follow up, 3.5% (7/199; six HIV positive) patients developed invasive carcinoma after 13-108 months and 112 (56%) patients relapsed condylomas. HIV and anal co-infection were identified as independent risk factors (P < 0.01) for HGD and cancer: odd ratio (95% confidence interval) of 9.4 (2.4-37.4) and 3.67 (0.95-14.2), respectively. LC densities in anal mucosa were lower in patients with invasive carcinoma than in controls. CONCLUSION: The risk of invasive carcinoma in HPV-infected patients is increased by HIV and anal co-infection. Decreases in LC numbers in anal mucosa may favour this outcome.

New Microbiol. 2004 Jan;27(1):65-9.

Identification of human papilloma viruses in male dysplastic genital lesions.

Dianzani C, Calvieri S, Pierangeli A, Degener AM. Institute of Dermatological Clinic, Section of Virology, "La Sapienza" University, Rome, Italy.

The association of Human Papillomaviruses (HPV) DNA with female genital lesions has been widely documented whereas little has been reported about male genital pathologies. The aim of this work was to investigate the presence of HPV DNA and the genotype involved in male dysplastic genital lesions. All samples were analysed by polymerase chain reaction (PCR) to amplify HPV E1 and L1 genes. The PCR products were subjected to restriction fragment length polymorphism (RFLP) to determine the HPV genotype. We analysed 209 male genital biopsies from different lesions: mostly from acuminate condylomata and from Buschke-Lowenstein tumours, Bowen papulosis, leukoplakia of the glans, scrotal lymphangioma, penile horn and penile/perianal verrucous carcinoma. Our results revealed the constant presence of viral DNA in genital condylomata, mainly associated with low risk HPV; the presence of the same genotypes was also detected in some of the examined rare pathologies.

Microbiol Mol Biol Rev. 2004 Jun;68(2):362-72.

Pathogenesis of human papillomaviruses in differentiating epithelia.

Longworth MS, Laimins LA. Department of Microbiology-Immunology, The Fineberg Medical School, Northwestern University, 303 E. Chicago Ave., Chicago, IL 60611, USA.

Human papillomaviruses (HPV) are the etiological agents of cervical and other anogenital malignancies. Over 100 different types of HPVs have been identified to date, and all target epithelial tissues for infection. One-third of HPV types specifically infect the genital tract, and a subset of these are the causative agents of anogenital cancers. Other HPV types that infect the genital tract induce benign hyperproliferative lesions or genital warts. The productive life cycle of HPVs is linked to epithelial differentiation. Papillomaviruses are thought to infect cells in the basal layer of stratified epithelia and establish their genomes as multicopy nuclear episomes. In these cells, viral DNA is replicated along with cellular chromosomes. Following cell division, one of the daughter cells migrates away from the basal layer and undergoes differentiation. In highly differentiated suprabasal cells, vegetative viral replication and late-gene expression are activated, resulting in the generation of progeny virions. Since virion production is restricted to differentiated cells, infected basal cells can persist for up to several decades or until the immune system clears the infection. The E6 and E7 genes encode viral oncoproteins that target Rb and p53, respectively. During the viral life cycle, these proteins facilitate stable maintenance of episomes and stimulate differentiated cells to reenter the S phase. The E1 and E2 proteins act as origin recognition factors as well as regulators of early viral transcription. The functions of the E5 and E1--E4 proteins are still largely unknown, but these proteins have been implicated in modulating late viral functions. The L1 and L2 proteins form icosahedral capsids for progeny virion generation. The characterization of the cellular targets of these viral proteins and the mechanisms regulating the differentiation-dependent viral life cycle remain active areas for the study of these important human pathogens.

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Zhonghua Nan Ke Xue. 2004 Mar;10(3):237-9.

Laboratory research of the influence of keyouling on the proliferation of human prepuce epidermis cells and condyloma acuminatum cells.

HPV Sexually Transmitted Disease - Article in Chinese

OBJECTIVE: To discuss the mechanism of the Chinese medicine Keyouling in the treatment of condyloma axuminatum (CA). METHODS: Human prepuce epidermis cells and CA cells were primarily cultured and subcultured. We determined the proliferation of human prepuce epidermis cells and CA cells, and observed the influence of Keyouling with different concentrations on the proliferation of human prepuce epidermis cells and CA cells by means of MTT colourimetry assay. RESULTS: The absorbance was directly proportional to the numbers of human prepuce epidermis cells (r = 0.9850, P < 0.001) and CA cells (r = 0.9892, P < 0.001). Keyouling had no effect on proliferation of the human prepuce epidermis cells, but it had significant inhibition on CA cells. The concentrations of Keyouling bore negative correlation with the proliferation percentage of CA cells(r = -0.4124, P < 0.01). CONCLUSION: Keyouling can significantly restrain the growth and proliferation of CA cells but has no damaging effect on normal organic cuticle cells. It is suggested that Keyouling might have anti-HPV effect.

Dermatol Surg. 2004 Apr;30(4 Pt 2):604-9.

Human papillomaviruses in transplant-associated skin cancers.

Stockfleth E, Nindl I, Sterry W, Ulrich C, Schmook T, Meyer T. Department of Dermatology, Charite, University of Berlin, Germany. Eggert.Stockfleth@charite.de

BACKGROUND: Human papillomavirus (HPV) infection has been suggested to be involved in the development of nonmelanoma skin cancer, the most common malignancy after solid-organ transplantation. OBJECTIVE: The objective of this study was to analyze the prevalence of different HPV types in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) of transplant recipients and nonimmunosuppressed patients. METHODS: To include the complete spectrum of HPV types in skin lesions, a comprehensive polymerase chain reaction assay with five different primer combinations was used. RESULTS: For SCC, HPV DNA was detected more frequently in tumors of transplant recipients (12/16, 75%) than of nonimmunosuppressed patients (7/19, 37%). In contrast, the HPV detection rate was similar in BCC specimens (4/8 or 50% in transplanted patients; 27/56 or 48% in nonimmunosupressed patients). Overall, 22 different HPV types were identified. HPV types 5 and 8 were detected predominately in SCC from transplant recipients. The amount of viral DNA was slightly higher in SCC of transplanted than in nonimmunosuppressed patients, but much lower than in both cutaneous and genital warts. CONCLUSIONS: Cutaneous infections with HPV5 and HPV8 may represent an increased risk for SCC development in transplant recipients. The mechanisms by which these viruses may contribute to skin cancer development still remain unclear.

Br J Cancer. 2004 Mar 8;90(5):1025-9.

A population-based study on the risk of cervical cancer and cervical intraepithelial neoplasia among grand multiparous women in Finland.

Hinkula M, Pukkala E, Kyyronen P, Laukkanen P, Koskela P, Paavonen J, Lehtinen M, Kauppila A. Department of Obstetrics and Gynecology, University of Oulu, PL 24, FIN-90029 OYS, Finland. marianne.hinkula@oulu.fi

Previous studies suggest that high parity increases the risk of cervical cancer. We studied the risk of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN3) in a Finnish cohort of grand multiparous (GM) women (at least five children) with low prevalence of sexually transmitted infections (STI). The Finnish Cancer Registry data revealed 220 CC and 178 CIN3 cases among 86 978 GM women. Standardised incidence ratios (SIR) were calculated from the numbers of observed and expected cases. Interval analyses by parity, age at first birth and average birth interval were done using multivariate Poisson regression. Seroprevalence of human papillomavirus (HPV) 16 and Chlamydia trachomatis was tested among 561 GM women and 5703 women with 2-4 pregnancies. The incidence among GM women was slightly above the national average for squamous cell carcinoma of cervix uteri (SIR 1.21, 95% CI 1.05-1.40) and CIN3 (1.37, 95% CI 1.17-1.58), but lower for adenocarcinoma (SIR 0.77, 95% CI 0.52-1.10). The seroprevalence of HPV16 and Chlamydia trachomatis among GM women was lower than in the reference population, except among those women who had their child under age 19. Age under 20 years at first birth increased the risk of CC and CIN3 especially in premenopausal GM women, while increasing parity had no effect. The small relative risks of CC and CIN3 among GM women in our study as compared to studies from other countries can be explained by the exceptionally low prevalence of STIs in Finnish GM women. The observed SIRs between 1.2 and 1.4 should be interpreted to represent increased risk attributable to grand multiparity. The increased incidence of CC and CIN3 among young GM women suggests causal association to HPV 16 and Chlamydia trachomatis infections.

Int J Gynaecol Obstet. 2004 Feb;84(2):156-61.

HPV prevalence among partners of women with cervical intraepithelial neoplasia.

Rosenblatt C, Lucon AM, Pereyra EA, Pinotti JA, Arap S, Ruiz CA. Urology Division, University Hospital, Sao Paulo University Medical School (USP), Sao Paulo, Brazil.

OBJECTIVES: The objective of this study was to find HPV DNA incidence in women with CIN and normal women and in their respective partners, as well as the relation between the virus groups found in women with CIN or normal women and in their respective partners. METHODS: Partners of 30 women with CIN at several grades and of 60 normal women were prospectively assessed. In men, HPV search was performed by collecting samples through penile scraping for Hybrid Capture, followed by peniscopic evaluation and biopsy of acetowhite lesions. RESULTS: The presence of HPV DNA in male partners does not necessarily implicate the presence of HPV or even CIN in their female partners. CONCLUSIONS: If these results are confirmed by other authors, obtaining a peniscopy, a penile biopsy, and a HPV DNA search in partners that present with no clinical lesions, but in couples with women having CIN, would not be warranted.

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