Biology of the papillomavirus infections: V. Vaccine developments]

Several genotypes of human papillomaviruses (HPV) are recognised as aetiologic factors for cervical cancer, and viral DNA account for more 99% of cases. Thus, prevention of HPV infection by, for example, types 16 and 18, should reduce the world-wide incidence of cervical cancer. Many strategies are being developed for the control of HPV-associated lesions of the uterine cervix: prophylactic vaccines which elicit neutralizing antibodies to prevent HPV infection, and therapeutic vaccines which induce a T-cytotoxic response to early viral oncoproteins. Experimental trials are being conducted to test mucosal immunization with an ideal antigen delivery system. Vaccination strategies elicit a protective antibody response in animal species, but in humans, strategies which are likely to be effective in the control of HPV-associated preneoplastic and neoplastic lesions of the uterine cervix are still under investigation.     

Malpighian epithelia and papillomavirus infections]

Human papillomaviruses (HPV) are a large group of DNA viruses, with over 60 types identified to date, which can cause the development of benign tumors in the skin and mucosal squamous epithelia. Most of these tumors regress spontaneously but some, especially in the mucosal membranes, become malignant. HPV types with a high risk for inducing malignancies (e.g. 16 and 18) are the subject of increasing interest. HPVs are both host-specific and tissue-specific: some types preferentially infect specific epithelia, giving rise to lesions with distinct topographic characteristics. HPVs are difficult to study because they do not replicate in available in vitro models. In vivo, HPVs replicate well in epithelial cells undergoing terminal differentiation, e.g. in keratinized cells. Some 40 different types have been reported in epidermal keratinocytes, the most common being types 1 and 2 which produce large amounts of viral antigens and viral particles. In contrast, HPVs replicate poorly in the weakly keratinized squamous epithelia which line the digestive, respiratory, and genital tracts. Junctional epithelia, e.g. on the uterine cervix, are especially prone to HPV infection. The most prevalent HPV types in benign genital lesions are types 6 and 11, whose characteristic features include extrachromosomal DNA and production of only small amounts of viral antigens. The profound nuclear and cytoplasmic changes induced by HPVs lead to the formation of ko?locytes which are found mainly in the granular layer of epithelia and have been especially well described in the uterine cervix and vagina. HPV epithelial tumors are squamous cell carcinomas that often harbor HPV types 16 and 18; this is especially true of cervical intraepithelial neoplasias.(ABSTRACT TRUNCATED AT 250 WORDS)     

Patterns of genotype distribution in multiple human papillomavirus infections.

The relationship between severe-grade cervical lesions and clusters of human papillomavirus (HPV) genotypes in a taxonomic classification was surveyed in 232 women with previous abnormal cytology. HPV co-infections were clustered according to phylogenetic criteria. Multiple infections were detected in 22.0% of the entire sample. Clade A10 (represented by HPV-6 and HPV-11) appeared more frequently in multiple infections than clade A9, which was represented by five of the most common high-risk types, including HPV-16. Although HPV-16 was the most frequent genotype, it was not more prevalent in multiple infections. Abortion and two or more sexual partners were risk-factors associated with HPV co-infections. Severe cervical dysplasia was associated with co-infections with oncogenic types from different clades, with the association being significant for the high-risk clades A7 and A9.     

Human papillomavirus infections and oral tumors

In the past 20 years, there has been an increasing interest in human papillomaviruses (HPV) because of their potential role in the pathogenesis of malignant tumors. In 1983, we published the first evidence that HPV might be involved in oral squamous cell carcinomas. The identification of morphological similarities between oral and cervical mucosa lead us to this original proposal. In a recent meta-analysis, HPV was indeed confirmed as an independent risk factor for oral carcinoma. To date, totally more than 100 types of HPV have been identified. As in anogenital cancers, HPV type 16 is the most prevalent type in oral carcinomas. The benign oral lesions, associated with HPV infection, include squamous cell papilloma, condyloma acuminatum, verrucca vulgaris and focal epithelial hyperplasia (FEH). Papillomas and condylomas are mostly caused by HPV type 6 or 11, while oral verrucas are associated with the skin types 2 or 4. A family history of FEH has been suggested. The FEH lesions are caused by HPV types 13 and 32, only detected in oral epithelium. In immunocompromised patients, benign HPV-induced lesions are characterized by atypical morphology and the simultaneous detection of multiple HPV types. Oral benign HPV lesions are mostly asymptomatic, and may persist or regress spontaneously.     

Toxoplasmosis in the Republic of Senegal. Sero-epidemiological survey

The presence of Toxoplasmosis in Senegal was investigated by the detection of IgG antibodies. 415 samples were obtained from healthy subjects from different regions of the country. In subjects of over 30, a greater number were found positive for IgG antibodies if they lived in a humid climate (25% in Northern Senegal, 57.7% in eastern Senegal). In Dakar 33.3% of the pregnant women studied had antibodies. This study confirms the presence of Toxoplasmosis in Senegal.     

HIV infections. Problems of morphologic diagnosis]

Considerable ultrastructural changes in the lymphoid cells of immunocompetent organs as well as in the epithelial and stromal cells of the rectum--the organ of the first contact with the virus in some cases--are found in HIV-infection. These alterations are of a quantitative nature and are the indications of important disturbances of the water-salt and protein metabolism. Changes in the lymphocytes and plasmacytes of the rectum lamina propria result in the damage to local immune defense. The presence of tubuloreticular and tubulo-annular structures in various cells of the rectum and lymphoid organs which are clearly seen in the biopsy material is most likely a characteristic sign of HIV-infection at its terminal stage.     

Involvement of human papillomavirus infections in prostate cancer progression

High-risk human papillomaviruses (HPVs) are sexually transmitted and have been associated with several human carcinomas especially cervical and colorectal. On the other hand, a small number of studies have examined the presence of high-risk HPV in human prostate cancer tissues. Currently, the presence and role of high-risk HPV infections in prostate carcinogenesis remain unclear because of the limited number of investigations. This raises the question whether high-risk HPV infections play any role in human prostate cancer development. However, other investigators and our group were able to immortalize normal and cancer prostate epithelial cells in vitro by E6/E7 of HPV type 16. In this paper, we propose the hypothesis that normal and cancer prostate epithelial cells are susceptible to persistent HPV infections; therefore, high-risk HPV infections play an important role in the progression of prostate cancer. We believe that an international collaboration of epidemiological studies and more molecular biology investigations are necessary to answer these important questions.     

High risk genital papillomavirus infections are not spread vertically

The Medline‐indexed literature on risk factors for HPV infection and HPV transmission is critically reviewed. Principles for assay validation and interpretation, reliability of different study designs and principles for interpretation of conflicting reports are discussed. The conclusions arrived at can be summarised as: (1) There is overwhelming epidemiological evidence that the only quantitatively important mode of transmission of infection with oncogenic genital HPV types is sexual. (2) There is also evidence that benign genital HPV types can be transmitted sexually, but the epidemiological data on the benign virus types are less extensive and less clear. (3) Perinatal HPV transmission is unequivocally demonstrated only for the rare disease juvenile respiratory papillomatosis. Copyright © 1999 John Wiley & Sons, Ltd.     

Preventing genital infections with human papillomavirus: lessons learned from the HIV epidemic.

Despite the major differences in the clinical epidemiology of HIV and HPV infections, several lessons learned from the HIV epidemic may be relevant to future prevention of HPV infection. There has been a paradigm shift in conceptualizing the epidemiology of STDs; targets of prevention now include: (1) determinants of exposures of susceptibles to infectious persons; (2) the efficiency of transmission; and (3) the duration of infectiousness. Lessons learned that may be potentially relevant to HPV prevention include: (1) advances in treatment of HIV have been rapidly adopted, whereas advances in prevention have not; (2) therapeutic and preventive trials have been too brief in duration, sometimes failing to adequately address major problems with relapse that become evident later; and (3) involvement of affected individuals and populations in research and prevention efforts has been essential and useful. Specific suggestions for HPV prevention efforts are discussed.     

Prevalence of human papillomavirus infections among heterosexual men and women with multiple sexual partners.

A prospective study of 65 men and 111 women with multiple heterosexual partners was designed to assess the prevalence and potential risk factors of genital human papillomavirus (HPV) infections. In addition, the HPV reservoir in genital, rectal, and oral mucosa was examined. The specimens for the detection of HPV DNA were taken from different sites such as the urethra and coronal sulcus (men), cervix and labia minora (women), anus, rectum, tongue, and buccal mucosa (both men and women). Women underwent speculum examination and colposcopic evaluation of the anogenital region, and a smear for routine cytological classification was also taken. In men, the anogenital region was examined clinically and colposcopically. The polymerase chain reaction (PCR) was used for the detection of HPV types 6/11, 16, 18, and 33. A high prevalence of HPV infection at one or more sites was detected, in 32% of the male and in 23% of the female participants. Seventeen percent of the male distal urethral specimens were positive for HPV DNA. From the female cervical specimens 14% were found positive. Ten proctal specimens (five men and five women) were positive for HPV DNA without any discernible lesion. The persons from whom these samples were taken denied anal insertive intercourse. No oral manifestation of HPV infection was detected. In both men and women a difference between HPV DNA-positive and -negative persons was not found in relation to known risk factors associated HPV infection.(ABSTRACT TRUNCATED AT 250 WORDS)