Immunology of papillomavirus infection

Studies of the immunology of papillomavirus infection have come of age. Synthetic virus-like particles have been validated as vaccines for several animal papillomaviruses, and have been used to map the sero-epidemiology of human papillomavirus infection and to define papillomavirus neutralizing antibodies. Induction of cell-mediated immunity to papillomavirus early proteins is poised to become a therapeutic approach to papillomavirus infection. Studies on the immune response to papillomavirus proteins in keratinocytes are shedding light on the immunological consequences of antigen presentation by epithelial cells.     

Anogenital papillomavirus infection and neoplasia in immunodeficient women

This article reviews the impact of infection with human immunodeficiency virus (HIV) on HPV infections and HPV-associated lesions of the female anogenital tract. Studies investigating HPV infections in HIV-seropositive women are presented as well as the possibility that HIV can influence HPV expression directly through molecular interactions between viral genes and indirectly through immunosuppression. Studies linking HIV infection to invasive cervical cancer and cervical intraepithelial neoplasia are reviewed; recommended protocols for cervical cancer screening in HIV-seropositive women for cervical disease also are presented.     

Psychological aspects of genital human papillomavirus infection: a preliminary report

Genital human papillomavirus (HPV) infection can lead to self-inflicted blame and hypochondriac fears as well as to problems with sexuality. The aim of this study was to assess the psychological and psychodynamic aspects of patients with widespread genital HPV infection entering into a clinical trial in which they were randomly assigned to three treatment groups: CO2 laser ablation, intramuscular interferon-alpha, CO2 laser ablation plus intramuscular interferon-alpha. Fifty-one patients were studied. Patients were asked to take a series of questionnaires which included a self-rating questionnaire for gathering information on sexuality, emotional relationship with the partner and social life. A visual analog scale was used to rate intensity of pain during sexual intercourse. Each patient went also through an in-depth interview with a clinical psychologist and filled out two personality tests to measure depression (CDQ = IPAT depression test) and anxiety (ASQ = IPAT anxiety test). Results indicated a high percentage of sexual impairments after therapy (28 cases), presence of fear of cancer (14 cases) and worsenings in the emotional relationship with the partner. No difference was found among groups of treatment.     

Humoral immune response to human papillomavirus infection

Nematodes are known to be a useful system for studies of comparative development. Here we perform a molecular phylogenetic analysis to allow for the independent interpretation of the developmental and morphological changes observed among a selected set of nematode species. Our molecular phylogenetic analysis is based on coding regions of the genes for RNA polymerase II, the small subunit rRNA and an expansion segment of the large subunit rRNA. Sequences were compared from five species in the family (Rhabditidae) that includes the developmental model organism Caenorhabditis elegans and from an outgroup taxon Aduncospiculum halicti (Diplogasterina). The phylogenetic analysis does not support the monophyly of the subfamily Mesorhabditinae and identifies the unnamed strain PS1010 as a sister taxon of C. elegans despite its morphologically divergent buccal capsule. On the basis of the inferred framework, we can begin to interpret the evolution of vulval development and of morphological differences among these nematode species.     

Detection of human papillomavirus DNA and clinicopathological study of vulvar human papillomavirus infection

We studied 217 vulvar HPV infection patients by clinically, pathologically, and virologically. From 90.6% of the cauliflower-like vulvar lesions and 29.7% of the papillomatous and finger-like lesions, we detected HPV 6/11 DNA by dot blotting hybridization. The patients in 90.0% of the cauliflower-like group and 9.8% of the papillomatous and finger-like group had a high risk factor to intercourse with different sex partners (P < 0.0001). The pathological characteristics, nature history, and response to treatment were different. According to clinical, pathological, and virological findings divided three types: vulvar HPV infection type 1 (or condylomata acuminata), vulvar HPV infection type 2, and vulvar HPV infection type 3.     

Human papillomavirus infection and esophageal cancer: a nationwide seroepidemiologic case-control study in Sweden

BACKGROUND: Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. AIM: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. SPECIMENS: Thirty paraffin wax embedded human gastric adenocarcinomas. METHODS: FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. CONCLUSIONS: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.     

Characteristic but unfamiliar--the cowpox infection, transmitted by a domestic cat

STUDY OBJECTIVE: The aim of this study was to determine the prevalence of stroke survivors in a health district population aged 55 years and over. DESIGN: This was a point prevalence study using two-stage postal questionnaires sent to an age stratified random sample of the population. SETTING: A district health authority in northern England with a resident population of 723,000. SUBJECTS: Altogether 18,827 residents aged 55 years or over. MAIN RESULTS: Prevalence was found to increase with age and, apart from the very elderly, males had a higher prevalence than females. Overall prevalence was found to be 46.8/1,000 (95% CI 42.5, 51.6). 23% of respondents reported full recovery from stroke. Cognitive impairments (33%), problems with lower limbs (33% for right leg; 27% for left leg) and speech difficulties (27%) were the most common residual impairments. CONCLUSIONS: Current guidelines to purchasers on the provision of services to those who have had a stroke may under-estimate prevalence rates by as much as 50%. This could lead to a shortfall in provision of services designed to support people in the months and years following their stroke.     

Effect of HIV infection on the natural history of anal human papillomavirus infection

OBJECTIVE: To identify risk factors for the detection of prevalent and incident anal human papillomavirus (HPV) infection, and HPV persistence among HIV-seropositive and seronegative homosexual men. DESIGN: Longitudinal study of 287 HIV-seronegative and 322 HIV-seropositive men attending a community-based clinic. METHODS: Subjects underwent an interview and examination; specimens were collected for HIV serology and assessment of anal HPV and HIV DNA. RESULTS: Anal HPV DNA was detected at study entry in 91.6% of HIV-infected men, and 65.9% of men not infected with HIV. HPV detection was associated with lifetime number of sexual partners and recent receptive anal intercourse (HIV-seronegative men), decreased CD4+ lymphocyte count (HIV-seropositive men), and anal warts (all men). Among men negative for HPV at study entry, subsequent detection of HPV was associated with HIV, unprotected receptive anal intercourse, and any sexual contact since the last visit. Among men positive for HPV at study entry, subsequent detection of additional HPV types was more common among HIV-seropositive men. Becoming HPV negative during follow-up was less common among men with HIV or high HPV levels at study entry. Among those with HIV, HPV persistence was associated with presence of anal HIV DNA, but not with CD4+ lymphocyte count. CONCLUSIONS: Risk of anal HPV infection appears to increase with sexual exposure, epithelial trauma, HIV infection and immune deficiency. Incident infection may result from recent sexual exposure or reactivation of latent infection. Further studies are needed to elucidate the mechanism by which HIV DNA in the anal canal increases the risk of HPV persistence.     

Molecular methods for the detection of human papillomavirus infection

HPVs are small DNA tumor viruses with an icosahedral virion structure. All members of the genus cause diverse benign lesions, and some members promote the development of carcinoma. The viruses do not replicate in culture without extraordinary measures, and virtually all studies to date have used molecular methods to elucidate their biology and natural history. Tests of choice for detecting HPV from clinical specimens are based on nucleic acid probe technology. Until recently, most epidemiologic and molecular studies employed Southern blot (SB), dot blot (DB), and in situ hybridization (ISH). With the exception of ISH, which continues to have many uses and a strong following in the pathology community, SB and DB have been essentially replaced by polymerase chain reaction (PCR) and the Hybrid Capture System (HCS). These newer in vitro probe tests have proven to be accurate and robust workhorses for epidemiologic and clinical use. Automation promises to revolutionize HPV testing in the near future and will allow cost-effective mass screening worldwide.     

Immunohistochemical study on human papillomavirus infection of the vulva

Two hundred and sixteen cases of human papillomavirus infection of the vulva from 1984 to 1991 in the Affiliated Hospital of Qingdao Medical College were reviewed, and were immunohistochemically studied by ABC method to detect HPV-Ag. The results showed that the demonstration of diagnostic koilocytes is very important in diagnosis of HPV infection in routine tissue slides examination. But in cases of atypical morphological changes; when diagnostic koilocytes were not formed in early stage, the demonstration of brown color granules in the nuclei of prickle cells is very diagnostic for positive HPV infection. In occasional cases, the diagnostic koilocytes do not demonstrate brown color granules in their nuclei. The explanation is that HPV-Ag was exhausted during metabolism. Besides, the cell membrane of basal cells are stained with brown color granules, while the morphological changes of upper layers of squamous epithelium have not appeared yet, therefore, there were no HPV-Ag positive reactive cells. It is probably showed that the HPV-Ag is primarily formed and appeared in the cell membrane of basal cells.     

Perinatal transmission and maternal risks of human papillomavirus infection

We conducted a prospective study to investigate whether human papillomavirus (HPV) could be vertically transmitted to neonates. Pregnant women (N = 203) were tested for HPV DNA infection during the third trimester and again during labor prior to delivery. Their newborns (N = 203) were tested 1 to 3 days after delivery. Among the mothers, 12.3% (N = 25/203) typed HPV positive at either or both maternal specimen collection periods, whereas only 1.0% of the neonates (N = 2/203) typed positive. This low transmission rate may be due in part to the fact that 65% of mothers who were HPV positive during the third trimester tested HPV negative by labor/delivery. The higher frequency of risks associated with maternal HPV infection were similar to those found in studies of cervical dysplasia and cancer: younger age at first intercourse and first pregnancy, number of sexual partners, and longer duration in use of oral contraceptives. In addition, those who were past smokers and had a shorter recency and latency period in smoking were more likely to be detected with HPV.     

Persistent infection promotes cross-species transmissibility of mouse hepatitis virus

Persistent infection with mouse hepatitis virus (MHV) strain A59 in murine DBT (delayed brain tumor) cells resulted in the emergence of host range variants, designated V51A and V51B, at 210 days postinfection. These host range mutants replicated efficiently in normally nonpermissive Chinese hamster ovary (CHO), in human hepatocarcinoma (HepG2), and to a lesser extent in human breast carcinoma (MCF7) cell lines. Little if any replication was noted in baby hamster kidney (BHK), green African monkey kidney (COS-7), feline kidney (CRFK), and swine testicular (ST) cell lines. By fluorescent antibody (FA) staining, persistent viruses V10B and V30B, isolated at days 38 and 119 days postinfection, also demonstrated very low levels of replication in human HepG2 cells. These data suggest that persistence may rapidly select for host range expansion of animal viruses. Pretreatment of HepG2 cells with a polyclonal antibody directed against human carcinoembryonic antigens (CEA) or with some monoclonal antibodies (Col-1, Col-4, Col-12, and Col-14) that bind human CEA significantly inhibited V51B infection. Under identical conditions, little or no blockade was evident with other monoclonal antibodies (kat4c or Col-6) which also bind the human CEA glycoproteins. In addition, an antibody (EDDA) directed against irrelevant antigens did not block V51B replication. Pretreatment with the Col-4 and Col-14 antibodies did not block Sindbis virus replication in HepG2 cells or MHV infection in DBT cells, suggesting that one or more CEA glycoproteins likely functioned as receptors for V51B entry into human cell lines. To test this hypothesis, the human biliary glycoprotein (Bgp) and CEA genes were cloned and expressed in normally nonpermissive BHK cell lines by using noncytopathic Sindbis virus replicons (pSinRep19). By growth curves and FA staining, human CEA and to a much lesser extent human Bgp functioned as receptors for V51B entry. Furthermore, V51B replication was blocked with polyclonal antiserum directed against human CEA and Bgp. Under identical conditions, the parental MHV strain A59 failed to replicate in BHK cells expressing human Bgp or CEA. These data suggest that MHV persistence may promote virus cross-species transmissibility by selecting for virus variants that recognize phylogenetic homologues of the normal receptor.     

Bartonella henselae infection in immunocompetent patients: cat scratch disease

BACKGROUND: Cat scratch disease, whose etiologic agent is Bartonella henselae, is a benign disease in immunocompetent subjects, characterized by lymphadenopathy of prolonged course and occasional involvement of other organs such as liver, spleen, central nervous system, eye and lung. In immunocompromised patients, the infection is bacteremic and disseminated. AIM: To report Chilean cases of cat scratch disease. PATIENTS AND METHODS: Ten children (seven male, aged between 6 and 13 years old) with histologically or serologically confirmed cat scratch disease are reported. RESULTS: Lymphadenopathy location was pre auricular in four cases, axillary in two, inguinal in two and epitrochlear in two. Three children had fever over 39 degrees C and two had a parinaud syndrome. Nine children had a history of cat scratch and one of a cat byte. Six had an erythrocyte sedimentation rate over 40. Lymph node ultrasound examination was a useful diagnostic tool. Two patients had splenic granulomas. Lymph node biopsies were obtained in four cases, showing a suppurative granulomatous lymphadenitis in all and a positive Warthin-Starry stain in two. Serology, done in patients without histological confirmation was positive with titles ranging from 1:64 to 1:8192. All patients had a satisfactory outcome with regression of lymphadenopathy. CONCLUSIONS: Infections by Bartonella hemselae occur in the Chilean population and must be considered in the differential diagnosis of regional lymph node enlargement.     

Cholecystadenocarcinoma in a cat

A malignant neoplastic process originating from gall bladder epithelium was diagnosed in a 14-year-old, spayed female, domestic shorthair cat. The tumor produced widespread pulmonary and lymphatic metastases. The clinical and pathological manifestations are described. Neoplasia arising from the gall bladder epithelium is rarely reported in animals.     

Spontaneous peritonitis in a cirrhotic patient with a cat: Pasteurella multocida infection of the ascitic fluid

Spontaneous peritonitis due to Pasteurella multocida is exceptional. As far as we know only 11 other cases have been reported. We describe a 45 year old patient who presented with a spontaneous Pasteurella multocida peritonitis as the first complication of a previously undiagnosed cirrhosis. The patient used to play with his pet cat, not recalling having ever sustained any injury. Cultures of the cat's mouth grew the same strain of Pasteurella multocida than was found in the patient's ascitic fluid. The clinical findings of the previous cases, most of which were also related to non traumatic exposure to domestic animals, are here described. Pasteurella multocida in one potential agent in the cirrhotic patient presenting with spontaneous peritonitis, especially if in close contact with animals, cats being the most often carriers.     

Bentonite toxicosis in a cat from cat litter?

Peripheral i.v. cannulation is one of the most common procedures performed in hospitals. Expanding the nursing role to include i.v. cannulation has the potential to improve care. The individual practitioner is responsible for maintaining and updating such skills.     

Morphologic manifestations of human papillomavirus infection in the vulvar and anogenital region

Out of 235 patients discharged from the Department of Thoracic Surgery, Silesian Medical Academy, after treatment of primary spontaneous pneumothorax between 1981 and 1993, 232 (98.7%) answered our questionnaire and so were included in the study. Mean follow-up time was 10.4 years. No recurrence of the disease was reported by any of 79 patients who had been treated by surgical procedure/thoracotomy plus pleurectomy/, but 21 (14.3%) out of 147 treated by paracentesis reported a recurrence of pneumothorax. In 17 patients the recurrence was the first-time case, in 3 the second-time, in 1 the third-time. Out of 232 patients, 10 (4.3%) had a recurrence of pneumothorax on the opposite side. Achieving expansion of the lung, 80% of the patients reported no problems at all. Only 6 (2.6%) of the whole group stated they could no longer work in their profession because of the pneumothorax they had suffered in the past.     

Usefulness of hybrid capture HPV DNA assay as a diagnostic tool for human papillomavirus infection

The purpose of this study was to determine the usefulness of the hybrid capture HPV DNA assay, a new nonradioactive solution hybridization assay, as a diagnostic tool for human papillomavirus infection. In a total of 234 women, samples for the hybrid capture assay and polymerase chain reaction (PCR) assay were obtained by wiping a swab across the cervix and external os (either a Dacron swab or a cotton swab was used). The papanicolaou smear test (Pap smear) was carried out on all 234 women. Tissue samples for biopsy were obtained by colposcopy from 118 of the women. Fisher exact test was used for statistical analyses. Using the hybrid capture assay, HPV DNA of high- and intermediate-oncogenic-risk type was detected in 23 (13.9%) of 166 samples from women with Pap smear Class I or II, and 48 (70.6%) of 68 with Pap smear Class III, IV or V (p < 0.0001). The HPV DNA type was detected in 18 (29.0%) of 62 samples from those with no evidence of cervical intraepithelial neoplasia and 44 (78.6%) of 56 with cervical intraepithelial neoplasia or squamous cell carcinoma (p < 0.0001). Correlation of the test results between the hybrid capture test and PCR was determined by using the 217 samples in which both test results were available (PCR test results were not obtainable in 17 samples. When PCR is set as a gold standard, the hybrid capture test has high sensitivity (74.6%) and specificity (92.7%). These findings suggest that the hybrid capture HPV DNA assay is a useful method for diagnosing HPV infection in the clinic.