Human Papillomavirus-associated Lesions Research Articles

Immuno-histochemical features of the cervical epithelium in human papillomavirus-associated cervical squamous intraepithelial lesions of high oncogenic risk degree

Immuno-histochemical features of the cervical epithelium in human papillomavirus-associated cervical squamous intraepithelial lesions of high oncogenic risk degree

Classical Article Evaluation of health-related quality of life the women with human papillomavirus-associated lesions of the cervical epithelium

Objective - to evaluate the health-related Quality of life the women with “lesser” abnormalities of cervical epithelium and patients with high grade squamous intraepithelial lesions (HSIL) associated with human papillomavirus (HPV) infection. Materials and methods. The investigation was performed 274 women of reproductive age, divided into two main groups: HPV infection (“lesser” abnormalities 202 patients and with HSIL - 20) and healthy women - 20. All the studied women of health-related quality of life by using the EQ-5D-5L. Results. Revealed a significant reduction in the level of health-related quality of life in the psychological and emotional components of the patients with “lesser” abnormalities of cervical epithelium and patients with HSIL associated with HPV infection (p

Management tactics for patients with benign human papillomavirus-associated cervical lesions at reproductive age

Management tactics for patients with benign human papillomavirus-associated cervical lesions at reproductive age

Human papilloma virus and anal associated lesions in men who have sex with men, HIV and non HIV-infected. First cross-sectional study in Uruguay

Human papilloma virus and anal associated lesions in men who have sex with men, HIV and non HIV-infected. First cross-sectional study in Uruguay

Substantial increase in the frequency of circulating CD4+NKG2D+ T cells in patients with cervical intraepithelial neoplasia grade 1

BackgroundThe NKG2D receptor confers important activating signals to NK cells via ligands expressed during cellular stress and viral infection. This receptor has generated great interest because not only is it expressed on NK cells, but it is also seen in virtually all CD8+ cytotoxic T cells and is classically considered absent in CD4+ T cells. However, recent studies have identified a distinctive population of CD4+ T cells that do express NKG2D, which could represent a particular cytotoxic effector population involved in viral infections and chronic diseases. On the other hand, increased incidence of human papillomavirus-associated lesions in CD4+ T cell-immunocompromised individuals suggests that CD4+ T cells play a key role in controlling the viral infection. Therefore, this study was focused on identifying the frequency of NKG2D-expressing CD4+ T cells in patients with cervical intraepithelial neoplasia (CIN) 1. Additionally, factors influencing CD4+NKG2D+ T cell expansion were also measured.ResultsClose to 50% of patients with CIN 1 contained at least one of the 37 HPV types detected by our genotyping system. A tendency for increased CD4+ T cells and CD8+ T cells and decreased NK cells was found in CIN 1 patients. The percentage of circulating CD4+ T cells co-expressing the NKG2D receptor significantly increased in women with CIN 1 versus control group. Interestingly, the increase of CD4+NKG2D+ T cells was seen in patients with CIN 1, despite the overall levels of CD4+ T cells did not significantly increase. We also found a significant increase of soluble MICB in CIN 1 patients; however, no correlation with the presence of CD4+NKG2D+ T cells was seen. While TGF-beta was significantly decreased in the group of CIN 1 patients, both TNF-alpha and IL-15 showed a tendency to increase in this group.ConclusionsTaken together, our results suggest that the significant increase within the CD4+NKG2D+ T cell population in CIN 1 patients might be the result of a chronic exposure to viral and/or pro-inflammatory factors, and concomitantly might also influence the clearance of CIN 1-type lesion.

Human papillomavirus-associated balanoposthitis – a marker for penile intraepithelial neoplasia?

The purpose of this study was to analyse, among men treated with diathermy, whether there was a difference in balanoposthitis between men with histopathologically benign human papillomavirus-associated lesions and those with penile intraepithelial neoplasia. Data were derived from patient material from a previously published study. Two clinically identical lesions from the same genital site were collected for analysis with routine histopathology and with nested PCR. In total, 292 men were included, of which 47 (16%) had penile intraepithelial neoplasia. Of those with penile intraepithelial neoplasia, 19/47 (40%) reported problems consistent with balanoposthitis, compared with only 15/245 (6%) patients with benign lesions (p < 0.0001). A statistical difference in percentage distribution was also seen regarding morphology (p = 0.001) and location (p = 0.0003) of the lesions among the men having benign lesions with and without balanoposthitis. It is not possible to take biopsies from patients with genital warts, but this study suggests that one probably should be more observant for genital dysplasia among those men with warts with a history of balanoposthitis than those with no such history.

Detection of autoantibodies to survivin in cervical mucus from patients with human papillomavirus-associated cervical cancer and precursor lesions

Objectives. To investigate the prevalence of mucosal autoantibodies to survivin in patients with human papillomavirus (HPV)-associated cervical cancer and precursor lesions.Methods. Cervical mucus from 117 HPV-associated cervical cancer, 102 high-grade squamous intraepithelial lesion (HSIL), 107 low-grade SIL (LSIL), and 80 normal controls were tested by ELISA using either full length recombinant survivin or survivin-derived peptides. Survivin expression in cervical tissue biopsies was studied by Western Blotting.Results. Cervical mucus from 33 cervical cancer (28.2%), 17 HSIL (16.6%), and 8 LSIL (7.4%) patients reacted with recombinant survivin. The IgA-class antibody response was significantly higher than that observed in the normal controls. The level of mucosal anti-survivin response was associated to the level and intensity of survivin expression in the different lesions. Finally, reactivity against a survivin Nt-derived peptide was found more frequently than reactivity against a Ct-derived peptide.Conclusions. IgA-class autoantibodies against survivin are present in a substantial proportion of cervical mucus from patients with HPV-associated cervical cancer, and precursor lesions. Mucosal anti-survivin response is positively associated with the level of survivin expression and the grade of cervical lesion.

BCL-2-related apoptosis markers in cutaneous human papillomavirus-associated lesions.

Human papilloma virus (HPV) is an etiological agent in benign and malignant epithelial tumors. Resistance to apoptotic stimuli by viral strategies represents an immunologic escape mechanism during virus-induced tumor development and is critical for efficient replication of the virus. The aim of the present study was to investigate a role of bcl-family proteins in the anti-apoptotic pathways modulated by low-risk HPVs in the development of benign HPV-associated cutaneous tumors. Forty lesional biopsy specimens from HPV-associated cutaneous lesions and 11 non-lesional control skin biopsies were studied by immunohistochemical analysis for the differential expressions of HPV antigens, the pro-apoptotic bax protein, and the anti-apoptotic bcl-2 and bcl-x proteins. Compared with the normal epidermis, bcl-2 and bcl-x expression were significantly reduced in the lesional epidermis. Bax was expressed in HPV-associated cutaneous lesions, although the expression did not reveal a significant deviation from that in normal skin. These findings indicate a discordant expression of bcl-2/ bcl-x and bax proteins in HPV-associated skin lesions and suggest that low-risk HPVs mediate other pathways that bypass the action of anti-apoptotic bcl-2 and bcl-x proteins. The presence of bax expression with a prominent decrease in bcl-2/ bax ratio and the lack of massive apoptosis in HPV-associated benign epithelial lesions may imply that interference with the pro-apoptotic proteins of bcl-family may constitute one of the several mechanisms mediated by HPV oncoproteins for the suppression of apoptotic process.

DNA vaccination prevents and/or delays carcinoma development of papillomavirus-induced skin papillomas on rabbits.

Malignant progression is a life-threatening consequence of human papillomavirus-associated lesions. In this study, we tested the efficacy of papillomavirus early-gene-based vaccines for prevention of carcinoma development of papillomavirus-induced skin papillomas on rabbits. Rabbit skin papillomas were initiated by infection with cottontail rabbit papillomavirus (CRPV). The papillomas were allowed to grow for 3 months without any treatment intervention. Rabbits were then immunized by gene gun-mediated intracutaneous administration of four DNA plasmids encoding CRPV E1, E2, E6, and E7 genes, respectively. All eight control rabbits receiving vector alone developed invasive carcinoma within 8 to 13 months. In contrast, only two of eight vaccinated rabbits developed carcinoma at 12 and 15 months, respectively. Papilloma growth was suppressed in the majority of vaccinated rabbits but not completely eradicated. These results indicate that gene gun-mediated immunization with papillomavirus early genes may be a promising strategy for prevention of malignant progression of human papillomavirus-associated lesions in humans.

Treatment of genital warts: an overview

Traditional treatments for human papillomavirus-associated lesions may be categorised into chemical, surgical and immunological therapies. Among chemical treatments, podophyllotoxin and trichloroacetic acid are the most commonly used. Cryotherapy, electrocautery and laser ablation constitute the main surgical approaches, while in the past decade interferons have been prescribed as an immunological treatment. The majority of current treatments are directed at lesion ablation. This clearly represents an insufficient treatment approach and should be replaced by, or used in conjunction with, a treatment which stimulates the host immunity in order to eradicate the virus. This would remove the source of re-occurrence and might also establish a stable immunity which would protect the patient from reinfection.

Activation of Local Cell-Mediated Immunity in Interferon-Responsive Patients with Human Papillomavirus-Associated Lesions

Successful immune response to viral infection, such as human papillomavirus (HPV) infection, involves presentation of viral antigens to the immune system, recruitment of T cells and macrophages, and activation of a diverse array of cytokines. Interferons (IFN) are known to exert immunomodulatory functions via activating these pathways. However, the presence of HPV can interact with this process. We employed a reverse transcription-polymerase chain reaction (RT-PCR)-based method to study this phenomenon in biopsies of patients responding well or poorly to IFN treatment. We found that responders show a delayed-type hypersensitivity (DTH) reaction after IFN treatment, in which TH1 cells (interleukin-2, IL-2, IFN-gamma) and macrophages/NK cells (CD16) predominate. Antigen presentation capability (e.g., upregulation of MHC molecules, cytokines) is also enhanced after IFN treatment in responders. The lack of upregulation of MHC molecules (HLA-DR, beta 2-microglobulin) and certain cytokines (IL-1 alpha, IL-2, IFN-gamma) in nonresponders may be due to the overexpression of HPV early (E7) gene in contrast to responders, where HPV late (L1) gene expression predominates. We concluded that differential HPV expression in infected cells can be responsible for an inappropriate IFN-mediated immune response.

Treatment failure of genital condylomata acuminata in women: role of the male sexual partner

The male sexual partners of women with genital condylomata acuminata are thought to be carriers of human papillomaviruses. It is therefore often recommended that both sexual partners be treated. We studied 360 women with genital warts to test the hypothesis that when the male partners of women with condylomata acuminata are treated, the treatment failure rate decreases. The male sexual partners of 180 of these women were examined and, if indicated, treated (treatment group). The 180 remaining male sexual partners were neither examined nor treated (control group). One hundred twenty-two (68%) men in the treatment group had human papillomavirus-associated lesions. The treatment failure rate of women was 16.7% in the treatment group and 18.9% in the control group. The difference is not statistically significant (p greater than 0.05). The results of this study do not support the hypothesis that the treatment failure rate of women with condylomata acuminata decreases if their male sexual partners are also treated.

Human immunodeficiency virus—induced immunosuppression: A risk factor for human papillomavirus infection

In a group of 92 women with genital condylomata, 15 (16.3%) human immunodeficiency virus-positive patients were found, whereas no case was detected in a control group of 100 women. The relative risk was greater than 19.28. Human immunodeficiency-positive status was associated with other parameters: lower age and parity, major frequency of induced abortions, and sexually transmitted diseases. Thus although human immunodeficiency-positive status seems to be a true risk factor in relation to the altered immunologic state, an indirect association cannot be discarded. Such patients should be screened closely for human papillomavirus infection and cervical cancer. Among human immunodeficiency-positive women, a more resistant behavior of human papillomavirus-associated lesions was detected (recurrence-persistence of 41.7% versus 12%), a fact that might also be in relation to the immunodepressed status.

Human papillomavirus--a study of male sexual partners.

Male sexual partners of a cohort of women with genital-tract abnormalities which were associated with human papillomavirus infection were examined for evidence of infection with human papillomavirus. Of the 214 male partners who were examined, 93.5% had visible genital lesions. Of the 196 lesions that were biopsied, 72.5% showed histological evidence of infection with human papillomavirus, and only 20.4% of subjects with histological evidence of human papillomavirus were aware of a lesion. An unexpectedly high proportion (6.1%) of lesions on which a biopsy was performed, particularly those with flat, red, indurated morphology, also showed histological evidence of penile intraepithelial neoplasia. This was not significantly more common among the partners of the women with cervical intraepithelial neoplasia than it was among the partners of the women with other evidence of genital human papillomavirus infection. Penile intraepithelial neoplasia was significantly (P less than 0.001) more common among subjects with no history of non-genital warts. We conclude that the male partners of women with human papillomavirus-associated lesions are very likely to be infected with human papillomavirus, and thus may act as a significant reservoir for the reinfection of their female partners. As the awareness of human papillomavirus-associated lesions was low among the male partners, colposcopic examination and treatment of their male partners, and/or barrier contraception, may be a necessary part of the management of women who are undergoing treatment for human papillomavirus-associated genital disease.

Prophylactic Topical 5-Fluorouracil following Treatment of Human Papillomavirus-Associated Lesions of the Vulva and Vagina

Prophylactic Topical 5-Fluorouracil following Treatment of Human Papillomavirus-Associated Lesions of the Vulva and Vagina

Genital Condylomas in Immunosuppressed Women: A Therapeutic Challenge

Of 30 immunosuppressed women with genital condylomas, 20 (67%) had associated neoplasia of the lower genital tract. We retrospectively studied 11 patients with flat condylomas confined to the cervix; all lesions were eradicated by conventional therapy. Three patients studied retrospectively and 16 studied prospectively had condylomatous lesions involving several sites within the lower genital tract. These lesions were unusually resistant to various treatment methods. Maintenance therapy with 5-fluorouracil (5-FU) cream resulted in a significantly higher control rate (6/7 patients, 86%) than could be achieved otherwise (2/9 patients, 22%; P less than .025). We conclude that ablative therapy by surgery or topical chemical agents followed by maintenance therapy with 5-FU cream may be the treatment of choice for condylomas and other human papillomavirus-associated lesions of the lower genital tract in immunosuppressed women.

Statement of Caution in the Interpretation of Papillomavirus-Associated Lesions of the Epithelium of Uterine Cervix

The recent discovery that papillomaviruses are associated with many of the morphologic abnormalities of the squamous epithelium of the uterine cervix previously classified as various forms of cervical intraepithelial neoplasia (dysplasia, carcinoma in situ, CIN) has created a great deal of confusion among pathologists. The facts are as follows: 1. The human papillomavirus-associated lesions (koilocytic atypia, warty atypia, “flat” or “inverted” condylomas, subclinical papillomavirus infection) are the most common abnormalities of cervical epithelium in young women, but may occur at any age. 2. In a significant proportion of women these lesions have been shown to be associated with other forms of cervical intraepithelial neoplasia and, in some, with invasive carcinoma. 3. At this time, the behavior of papillomavirus-associated lesions cannot be predicted on morphologic grounds, as is also true of other forms of intraepithelial neoplasia. For these reasons, it is the opinion of the undersigned that these lesions should be reported according to the degree of morphologic abnormality, within the framework of the customary reporting system used for precancerous epithelial lesions of the uterine cervix, such as dysplasia, carcinoma in situ, or CIN. The presence of the virus-associated component may be mentioned as a part of the microscopic diagnosis but should not modify the clinical approach to these lesions. Women bearing the virus-associated lesions should receive the same clinical and colposcopic evaluation, treatment, and follow-up as usually administered to women with conventional forms of cervical intraepithelial neoplasia, until more data on the natural history of these lesions are obtained.