Role Of Human Papillomavirus Infection Research Articles

Human Papillomaviruses Infection in Oral Squamous Cell Carcinoma And Oral Pre-cancer Lesions In Taiwan

Human papilloma viruses (HPV) infection is a significant risk factor for uterine cervical carcinoma. Many previous studies have also demonstrated the presence of HPVs in oral epithelia tissue. However, the role of HPV infection in oral squamous cell carcinoma (OSCC) is still controversy. The present study is to determine the frequency and type of HPV in OSCCs and oral pre-cancer lesions. Methods: DNA samples were collected from 51 OSCCs, 46 oral pre-cancer lesions and 90 normal control specimens by cytobrushings. Nested polymerase chain reaction (PCR), and gene-chip are used to identify multiple HPV types in our samples. Results: The positive rates of overall HPV types (14/46, P=0.0216, OR=2.844, CI=1.186-6.816) and of low- risk types (9/46, P=0.0096, OR=5.529, CI=1.597-19.14) are significantly higher in oral pre-cancer lesions than in control samples. The prevalence of high-risk type (11/51, P=0.0420, OR=2.819, CI=1.051-7.558) is significantly higher in OSCCs than in control but of overall types (13/51, P=0.1066, OR=2.244, CI=0.9266- 5.337) is not to reach the statistical significance.Conclusion: The high-risk HPV may play a role in OSCCs progression and the low-risk ones may associate with the oral pre-cancer lesions.

Preventable but not prevented: the reality of cervical cancer.

The incidence of invasive cervical cancer has decreased in the last 50 years in the developed countries substantially due to the use of routine pap smears. However, in the Asia-Oceanic region it continues to be high as screening programs are not established. Credit for starting cytology services in India goes to Professor P.N. Wahi of Agra. He became Founder President when about 34 cytologists got together in 1970 to form the Indian Academy of Cytologists. Since then cytology has spread through all parts of India. The Cytology Clinic in Cama & Albless Hospital was started in the same year. Since then over 100000 women have been screened. Approximately 1200 cases of pre- and early cancers have been detected and treated. Since 1982 we are aware of the important role of human papillomavirus infection. We diagnose it by cytology and colposcopy and histology. Facilities for polymerase chain reaction, in-situ hybridization and other virology studies are not available to us. CO2 laser treatment is found particularly useful in multicentric human papillomavirus disease. Since 1984 we have planned for a screening program for our State. We have a population of 78.9 million. Approximately 15 million women in the age group of 35-64 years have to be screened. The health care infrastructure is good with 36 medical colleges and over 35 district hospitals. Screening is planned in phases. Trained personnel are the key to a successful program. In the final analysis, cervical cancer is not just a biomedical disease. It has socio-cultural and economic implications.

A critique of cohort studies examining the role of human papillomavirus infection in cervical neoplasia.

A critique of cohort studies examining the role of human papillomavirus infection in cervical neoplasia.

Molecular biology of laryngeal squamous cell carcinoma.

Some of the mechanisms involved in neoplastic transformation and progression of laryngeal squamous cell carcinoma (LSCC) are discussed. Although tumor suppressor inactivation of p53 and p16 is common in these tumors (about 50% each), oncogenic activation is less well characterized. Cyclin D1 and epidermal growth factor receptor amplification have been reported in one-third and one-quarter of LSCCs, respectively, both related to advanced stages, whereas c-myc could be amplified in 13% of cases although without associated overexpression. The role of ras in LSCC is, at most, exceptional, and the role of human papillomavirus infection in these neoplasms could have been largely overestimated. The AIS (amplified in squamous carcinoma) gene has been recently proposed as the main oncogenic target in head and neck squamous carcinomas and is a promising line of investigation. This, along with the link that exists between p53 and INK4 suppressor pathways through ARF and MDM-2, and the role of the universal cdk inhibitors (the Cip/Kip family) in these neoplasms deserve further investigation. Not forgotten are the mechanisms leading to cell immortalization and invasive capabilities acquisition, some of which are also briefly described.

The causal relation between human papillomavirus and cervical cancer.

The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.

Human papillomavirus as a risk factor for oral squamous cell carcinoma: A meta-analysis, 1982-1997

Objective. Human papillomavirus (HPV) infection is a significant risk factor for uterine cervical carcinoma. However, the role of HPV infection in oral squamous cell carcinoma (OSCC) is less well defined. To determine the significance of the relationship of this virus in the progressive development of oral cancer, we estimated the risk of HPV detection in normal oral mucosa, precancerous oral tissue, and oral carcinoma using meta-analysis. Study design. Case reports and clinical series published in English-language journals were retrieved by searching MEDLINE (January 1980-August 1998). Review articles were also examined to identify additional studies. Studies that used biochemical, immunologic, microscopic, or molecular analyses to detect HPV in tissue or cells derived from normal oral mucosa (n = 25), benign leukoplakia (n = 21), intraepithelial neoplasia (ie, dysplasia and carcinoma in situ; n = 27), and oral cancer (n = 94) were included in the meta-analysis. Information on sample size, age, sex, method of tissue preservation (ie, fresh, frozen, paraffin-embedded), assay, primer amplification region (early, late), high-risk versus low-risk genotype, and use of tobacco or alcohol was abstracted by one author (C.S.M.). Results. Data from 94 reports that analyzed 4680 samples were included in the meta-analysis. Analyses made by means of a random-effects model with and without adjustments for assay sensitivity showed increased probability of HPV detection in tissue with precancerous and cancerous features compared with normal mucosa. The likelihood of detecting HPV in normal oral mucosa (10.0%; 95% confidence interval [CI], 6.1%-14.6%) was significantly less than of detecting benign leukoplakia (22.2%; 95% CI, 15.7%-29.9%), intraepithelial neoplasia (26.2%; 95% CI, 19.6%-33.6%), verrucous carcinoma (29.5%; 95% CI, 23%-36.8%), and OSCC (46.5%; 95% CI, 37.6%-55.5%). Adjustment of findings for differences in assay sensitivity indicated that these estimates may be conservative. Overall, HPV was between 2 and 3 times more likely to be detected in precancerous oral mucosa and 4.7 times more likely to be detected in oral carcinoma than in normal mucosa. The pooled odds ratio for the subset of studies directly comparing the prevalence of HPV in normal mucosa and OSCC was 5.37, confirming the trend observed in the overall sample. The probability of detecting high-risk HPVs in OSCCs was 2.8 times greater than that of low-risk HPVs. Conclusion. This meta-analysis indicates that HPV is detected with increased frequency in oral dysplastic and carcinomatous epithelium in comparison with normal oral mucosa. The findings provide further quantitative evidence that oral infection with HPV, particularly with high-risk genotypes, is a significant independent risk factor for OSCC. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:622-35)

Squamous Cell Carcinoma of the Eyelid and the Acquired Immunodeficiency Syndrome

We studied a case of squamous cell carcinoma of the eyelid in a 42-year-old homosexual man with the acquired immunodeficiency syndrome (AIDS) to explore the link between squamous cell carcinoma and human Papillomavirus infection. A rapidly growing, 3-mm lesion was removed from the right lower eyelid by excisional biopsy. Examination of the lesion confirmed squamous cell carcinoma. Polymerase chain reaction for human Papillomavirus 16 was positive. This case suggests a role for human Papillomavirus infection in the cause of squamous cell carcinoma in AIDS patients.

Cervical dysplasia in HIV-seropositive women: role of human papillomavirus infection and immune status.

In the present study we investigated the cytologic and colposcopic characteristics of a cohort of HIV-infected women, with the aim to determine a relationship between immunologic status and frequency and/or severity of cervical abnormalities. 21 women, who tested positive for the HIV antibody and who were admitted as outpatients because of various gynecologic complications or because of an HIV infection that was under regular clinical surveillance. A pelvic examination was performed and Papanicolaou smears were obtained from endocervix and ectocervix before colposcopic examination. Cytologic samples for human papillomavirus (HPV) detection by polymerase chain reaction were also collected. Results obtained in the group of HIV-infected women were compared with findings in a group of 473 seronegative women recruited consecutively from our outpatient population. Serum samples for T lymphocytes were drawn within 2 weeks of cytologic and colposcopic examination. CD4 and CD8 monoclonal antibodies were purchased from Becton Dickinson (Mountain View, Calif., USA). HIV-infected women had a significantly higher percentage of HPV DNA positivity with respect to the outpatient population (67 vs. 7%, respectively, p < 0.001). Analysis of cytologic specimens revealed 9 women (43%) with cytologic evidence of cervical dysplasia in the HIV-seropositive group vs. 23 (5%) of 473 in the outpatient population (p < 0.001). All the HIV-seropositive women with cervical dysplasia presented an associated HPV DNA positivity; in particular, the percentage of associated HPV DNA type 16 in cervical dysplasia was 78% (7/9 cases). In HIV-infected women, the evaluation of T lymphocyte subset distribution suggested a significant relationship between CD4+ cell decrease and severity of cytologic findings (p = 0.03). The HIV-infected women had a tenfold higher prevalence of both HPV infection and cervical dysplasia than the outpatient population; this increased risk seems to be limited mainly to those who also had genital HPV infection. The analysis of immunologic status confirmed previous observations that an impaired immune system results in increased cervical disease.

Interval between menarche and first sexual intercourse, related to risk of human papillomavirus infection

The purpose of this investigation was to study the occurrence of human papillomavirus (HPV) infection in relation to the interval between menarche and first intercourse. Two hundred eight subjects, aged 13 to 21 years, were recruited from an ambulatory adolescent clinic. Patients were excluded if they had a history of genital warts or an abnormal Papanicolaou smear. All subjects completed a self-administered questionnaire regarding demographics and their menstrual, sexual, and contraceptive histories. HPV infection was determined by in situ hybridization or changes consistent with HPV on a Papanicolaou smear, or both. The prevalence of HPV infection was 19.2%. The average interval between menarche and onset of sexual activity was 26.6 months for those who were found to have HPV infection compared with 35.7 months for those whose test results were negative ( p = 0.02). First sexual intercourse within 18 months of menarche was associated with a significant elevation of risk of HPV infection, in comparison with that in adolescents who postpone first intercourse 3 to 4 years after menarche. These data suggest that factors such as increased biologic vulnerability may play a role in HPV infections among adolescent women. (J P EDIATR 1994;125:661-6)

Significance of Human Papillomavirus-Induced Squamous Cell Carcinoma to Dermatologists

HUMAN PAPILLOMAVIRUS (HPV) is now recognized as the possible cause of many skin diseases, including verrucae, condyloma acuminatum, Bowen's disease, keratoacanthomas, bowenoid papulosis, squamous cell carcinoma (SCC) in epidermodysplasia verruciformis (EV) and in immunosuppressed patients, and SCC of the nail bed and periungual area.¹The reason for this ''epidemic'' of cutaneous HPV infection is unclear and requires further study. Because of the increased frequency of HPV infection seen in a dermatology practice, clinical dermatologists should be able to recognize the different clinical manifestations of cutaneous HPV infection, and should understand the implications of immunosuppression on HPV infection, the role of HPV infection in genital neoplasms, and the implications of HPV in the treatment of HPV-induced cutaneous SCC. Evidence has recently been accumulating that HPV is the significant factor in the malignant transformation of certain cutaneous neoplasms. The strongest evidence for the cutaneous oncogenic potential of HPV is found in

The Structure, Function, and Regulation of Papillomaviral Genes in Infection and Cervical Cancer

Publisher Summary This chapter summarizes developments in the understanding of the molecular biology of papillomaviral infection, with emphasis on the control of critical events in human papillomavirus (HPV) infection and cervical cancer at the level of viral gene transcription. It discusses papillomaviral replication systems and the genes involved in viral replication, and briefly reviews the interactions between viral and cellular proteins involved in neoplastic transformation. The chapter also describes cellular and viral factors involved in the control of papillomaviral gene expression, and speculates how they jointly interact to direct the expression of viral replication and transformation genes in active infection, viral latency, and cervical cancer. Progress in studies on the function of HPV genes not only has provided new insights on the role of HPV infection in cervical carcinogenesis, but also has established the molecular biology of genital HPVs as an exciting model for investigations on the molecular mechanisms of cell transformation, cell cycle control and transcriptional gene regulation.

Oral cancer and human papillomaviruses: Is there a link?

Cancer of the oral cavity accounts for almost 56,000 new cases in India each year totalling almost 30% of all cancer cases in the country. Despite the numerous advances in etiology and epidemiology, the mechanisms involved in oral carcinogenesis remain obscure. Current research has provided some provocative results, suggesting an association between human papillomavirus (HPV) and development of squamous cell tumors including oral cancer. Evidence has been presented showing HPV infection of the oral mucosa and its relation to neoplastic changes. However a clear cut association as is evident in the uterine cervix is not yet available. However, considering the many similarities between oral and cervical oncogenesis, many of the HPV induced changes in the cervix may also be applicable to the oral mucosa. This paper studies the evidence for the possible role of HPV infection in oral carcinogenesis, the uterine cervix as a model for HPV mediated carcinogenesis, and tries to determine if similar mechanisms could exist in both cases.

Epidermotropism of T cells correlates with intercellular adhesion molecule (ICAM1) expression in human papillomavirus (HPV)-induced lesions.

Adhesion molecules play an important role in inflammatory reactions. Among them, ICAM1, a ligand for the lymphocyte function-associated antigen (FLA1) of leucocytes, may be expressed by antigen-presenting cells and keratinocytes in various inflammatory disorders. As cell-mediated immune responses play a great role in HPV infections, we investigated the expression of ICAM1 and correlated it with the presence of LFA1-positive cells by immunohistochemistry on serial frozen sections of a series of non-regressing cutaneous and mucosal HPV-induced lesions. ICAM1 expression by keratinocytes was observed only in intensely infiltrated lesions of condylomas and laryngeal papillomas. Its induction was usually correlated with the presence of LFA1-positive cells (mainly CD8-positive cells) which were in close apposition to ICAM1-positive proliferative epithelial cells expressing also, in some cases, HLA-DR antigen. ICAM1 was not correlated with the presence of HPV DNA or viral antigen. In moderately infiltrated lesions, keratinocytes did not express ICAM1, and LFA1-positive cells were not observed in the epidermis. In all lesions, ICAM1 was more intense on endothelial cells than in normal skin; infiltrating cells (lymphocytes and dendritic cells) may also express this antigen but intraepithelial Langerhans cells were devoid of any labelling. These studies provide further evidence that T-lymphocyte mechanisms are important in the host response to HPV-induced lesions. ICAM1 expression correlates with a lesional infiltrate but not with HPV infection and probably results in a more efficient initiation of the immune reaction.

Oncogenesis of squamous carcinoma of the uterine cervix.

Carcinoma of the uterine cervix is the most frequent neoplasm among women in India, accounting for up to 85% of all female gynecological malignancies. In the United States, it accounts for about 48% of all female tumors and 4% of all cancer deaths of females. Epidemiological evidence suggests involvement of numerous risk factors in the etiology of cervical cancer, including sexual behavior, number of pregnancies, cigarette smoking, and venereal disease. Recent studies, however, tend to emphasize viral involvement in the development of cervical cancer along with concomitant cytogenetic and immunological changes. This review focuses on the roles of human papillomavirus infection, chromosomal abnormalities, and immune function changes in the pathogenesis of cervical carcinoma.

Detection of human papillomavirus-16 e6-oncoprotein in epithelial ovarian tumors samples of iraqi patients.

Background:Human papillomavirus (HPV) is the causal factor for cervical cancer. However, the role of HPV infection in ovarian cancer is unclear.Objectives:This study aimed to determine the presence of human papillomavirus-16 (HPV-16) in ovarian tumor tissues.Patients and Methods:This was a retrospective study, which included 61 Archived human ovarian tumor tissues embedded in paraffin blocks. The ovarian tumor tissues were divided into four groups. The first group was the malignant ovarian epithelial tumor group; it included 31 cases with invasive surface epithelial ovarian tumors. The second group was the borderline epithelial ovarian tumor group: it included four cases with borderline intermediate malignancy. The third group was the benign epithelial ovarian tumors group: it included 18 cases with benign epithelial ovarian tumors. The fourth group had functional ovarian cystic lesions: it included eight cases with non-neoplastic functional ovarian cysts. Sections were made from each of the paraffin embedded blocks and examined using immunohistochemistry to detect HPV 16-E6-oncoprotein in ovarian tumor tissues.Results:Out of the eight cases with functional cysts only one case (12.5%) expressed HPV. No HPV expression was seen in cases with benign and borderline tumors. Out of the 31 cases with one malignant surface epithelial ovarian tumor only three (9.67%) cases expressed HPV. There was no significant statistical difference in HPV expression among neoplastic and non-neoplastic ovarian tumors included in the present study (P= 0.476).Conclusions:HPV type 16 was detected in only 9.67% of malignant epithelial tumors. It appears that HPV infection plays a relatively minor role in the pathogenesis of ovarian carcinomas.