Patients With LR-HPV Infection Have a Distinct Vaginal Microbiota in Comparison With Healthy Controls.

Condyloma acuminatum (CA) is a benign epithelium hyperplasia mainly caused by human papillomavirus (HPV), which is now the second most common viral sexually transmitted infection (STI) in China. In total, 90% of CA patients are caused by the low-risk HPV 6 and 11. Aside from low-risk HPV infection there are likely other factors within the local microenvironment that contribute to CA and there has been related research before. In this study, 62 vaginal specimens were analyzed using 16S rRNA gene sequencing. The diversity of the vaginal microbiota was higher and the composition was different with LR-HPV infection. While the relative abundance of dominant Firmicutes was lower, Actinobacteria, Proteobacteria, and Fusobacteria phyla were significantly higher; at the genus level Gardnerella, Bifidobacterium, Sneathia, Hydrogenophilus, Burkholderia, and Atopobium were higher. This study firstly confirmed a more accurate and comprehensive understanding of the relationship between low-risk HPV infection and vaginal microbiota, in order to provide a theoretical basis for further research on the occurrence and development of CA.

Highlighting a Potential Pitfall: Positive Treponema pallidum Immunohistochemical Stain in a Patient Without Syphilis.

The Treponema pallidum antibody immunohistochemical (IHC) stain has improved our ability to detect the organism histologically. We present a case of a man with genital condyloma acuminatum with a positive T. pallidum IHC stain but negative T. pallidum serologies and no syphilitic symptoms. It has been shown that the T. pallidum antibody IHC can cross-react, staining other spirochetes, including Borrelia burgdorferi and the Brachyspira family of intestinal spirochetes. Because of the proximity of our patient's lesions to the anus, and the persistently negative T. pallidum serologies, we believe nontreponemal spirochetes colonized the condyloma, giving a false-positive T. pallidum IHC. This cross-reactivity is a potential diagnostic pitfall and is important for the dermatopathologist to recognize, thereby avoiding false diagnosis of syphilis.

Consideraciones prácticas de la anoscopia de alta resolución en pacientes infectados por el virus de la inmunodeficiencia humana / Practical considerations for high resolution anoscopy in patients infected with human immunodeficiency virus

El cáncer de ano, una enfermedad infrecuente en la población general, presenta una incidencia elevada y progresiva en ciertos grupos de riesgo, fundamentalmente en hombres que tienen sexo con hombres, y particularmente en aquellos con infección por el virus de la inmunodeficiencia humana. La anoscopia de alta resolución se considera actualmente la técnica estándar en el diagnóstico de la neoplasia intraepitelial anal, pero su uso protocolizado aún está por consensuar en los sistemas sanitarios. Aunque no está exenta de dificultades, es una técnica asequible que puede llegar a ser fundamental en el cribado del cáncer de ano y sus lesiones precursoras. Actualmente estamos estudiando la estrategia más efectiva para el manejo de las lesiones premalignas anales, y con esta publicación intentamos animar a otros grupos interesados en la reducción de una neoplasia epidemiológicamente en progresión

Anal cancer is uncommon in the general population, however its incidence is increasing significantly in certain risk groups, mainly in men who have sex with men, and particularly those infected with human immunodeficiency virus. High resolution anoscopy technique is currently considered the standard in the diagnosis of anal intraepithelial neoplasia, but at present there is no agreed standard method between health areas. High resolution anoscopy is an affordable technique that can be critical in the screening of anal carcinoma and its precursor lesions, but is not without difficulties. We are currently studying the most effective strategy for managing premalignant anal lesions, and with this article we attempt to encourage other groups interested in reducing the incidence of an increasing neoplasia

Chlamydia trachomatis infection in children: do not forget perinatal acquisition: a case report of a 7-year old girl, C. trachomatis infected, presumed sexually assaulted.

A 7-year old girl suspected of having been sexually abused owing to the presence of anal condyloma was found to be infected by Chlamydia trachomatis. Microbiological analysis and anamnesis were consistent with the infection having been acquired at birth. This case confirms that untreated infection acquired at birth can persist for months or years and highlights the value of examining those involved in the suspicion of sexual abuse of the child.

Transmission of Chlamydia and genital warts during sleepwalking.

A boy aged 15 years infected a girl of 13 years with Chlamydia and genital warts. The boy has been engaged in sexual activities for the last four years. There was no dispute that the boy had had sex with the girl. He was prosecuted but acquitted by the Court on the ground of 'defence of sleepwalking'. This is the first case where sexually transmitted infections like Chlamydia and genital warts have been transmitted sexually through sleepwalking. This case also raises the issues of underage sex and issues of confidentiality.

Expression of MDM2 protein and mRNA in condyloma acuminata.

In order to investigate the role of murine double minute 2 (MDM2) in cell proliferation and carcinogenesis in condyloma acuminatum (CA), immunohistochemistry and in situ hybridization were used to detect the expression of MDM2 protein and mRNA in normal skin and skin lesions of CA of vulva. PCR was also used to detect HPV types. The results showed that in 32 observed CA specimens, the expression of MDM2 protein and mRNA was detected in 18 (56.25%) and 22 (68.75%) respectively, while the co-expression of MDM2 protein and mRNA was found in 14. PCR results revealed that HPV6/11 and HPV16/18 subtypes were shown in 28(87.5%) and 4 (12.5%) respectively out of 32 CA specimens. Out of the 18 positive specimens expressing MDM2 protein, HPV6/11 subtypes were shown in 15 and HPV16/18 subtypes in 3. In 22 positive specimens expressing MDM2 mRNA, HPV6/11 subtypes were shown in 18 and HPV16/18 subtypes in 4. No expression of MDM2 protein and MDM2 mRNA was observed in normal skin. Our study indicated that the overexpression of MDM2 might be involved in malignant proliferation and carcinogenesis of CA.

Sexually transmitted infections in men.

The diagnosis and treatment of STDs is a common problem in primary care practice; however, newer diagnostic and therapeutic alternatives require physicians to be aware of evidence-based guidelines that are continuing to evolve. The treatment of STDs in men, in particular, is an area of evolving evidence because much of what is known is based on the treatment of STDs in women. Men represent unique challenges in diagnosis, evaluation, and follow-up that need to be considered in the treatment of urethritis, epididymitis, herpes genitalis, condyloma, prostatitis, and other syndromes. Screening for asymptomatic STDs is currently not recommended in the general population, but selected criteria can be used to identify a target population for screening in high-risk areas.

Drug treatment of common STDs: Part II. Vaginal infections, pelvic inflammatory disease and genital warts.

The Centers for Disease Control and Prevention (CDC) released new guidelines for the treatment of sexually transmitted diseases (STDs) in 1998. Several treatment advances have been made since the previous guidelines were published. Part II of this two-part series on STDs describes recommendations for the treatment of diseases characterized by vaginal discharge, pelvic inflammatory disease, epididymitis, human papillomavirus infection, proctitis, proctocolitis, enteritis and ectoparasitic diseases. Single-dose therapies are recommended for the treatment of several of these diseases. A single 1-g dose of oral azithromycin is as effective as a seven-day course of oral doxycycline, 100 mg twice a day, for the treatment of chlamydial infection. Erythromycin and ofloxacin are alternative agents. Four single-dose therapies are now recommended for the management of uncomplicated gonococcal infections, including 400 mg of cefixime, 500 mg of ciprofloxacin, 125 mg of ceftriaxone or 400 mg of ofloxacin. Advances in the treatment of bacterial vaginosis also have been made. A seven-day course of oral metronidazole is still recommended for the treatment of bacterial vaginosis in pregnant women, but intravaginal clindamycin cream and metronidazole gel are now recommended in nonpregnant women. Single-dose therapy with 150 mg of oral fluconazole is a recommended treatment for vulvovaginal candidiasis. Two new topical treatments, podofilox and imiquimod, are available for patient self-administration to treat human papillomavirus infection. Permethrin cream is now the preferred agent for the treatment of pediculosis pubis and scabies.

Assessment of archived paraffin-embedded cervical condyloma tissues for mycoplasma-conserved DNA using sensitive PCR-ELISA.

Clinically, it is important to detect mycoplasmas because these organisms have been implicated in gastric and ovarian cancer, pneumonia, postabortal fever, pelvic inflammatory disease, pyelonephritis, endometritis, urethritis, perinatal mortality, arthritis, spontaneous abortion, infertility and interference with sperm development and they act as cofactors catalyzing the HIV disease state. Recently, the combined polymerase chain reaction and enzyme-linked immunosorbent assay method targeting the consensus DNA of over 15 species of mycoplasmas was shown to be superior for the detection of mycoplasmas. The objective was to determine if there was an association between mycoplasmas and cervical neoplasia. Cervical tissues, histopathologically categorized by cervical intraepithelial neoplasia (CIN) grade, flat or exophytic, and acanthosis or koilocytotic, were used. The results showed that mycoplasmas DNA were present in 21.4% of the condyloma tissues and in 33.3% of condyloma tissues with CIN. In contrast, mycoplasmas DNA were not detected when there were no CIN. The presence or absence of human papillomavirus (HPV) did not make a difference. Mycoplasmas DNA were present in 40.0 and 12.5% of the exophytic and flat condylomas, respectively. A higher percentage of cervical tissues graded with slight koilocytosis had (P = 0.05) mycoplasmas DNA compared with tissues graded with moderate koilocytosis. The detection of mycoplasmas DNA in archived cervical condyloma tissues with CIN corroborated previous reports of an association between mycoplasmas and CIN. However, the association between mycoplasmas and the presence of HPV could not be made in this study.

[Precancerous and cancerous involvement of the uterine cervix. Results of a survey conducted by the "Genital Cancers" group of Ile-de-France, May 1990-May 1992, based on 8,805 biopsies]. / Pathologie précancéreuse et cancéreuse du col de l'utérus. Résultats d'une enquête conduite par le groupe "cancers génitaux" de PETRI, dans la région Ile-de-France, de mai 1990 à mai 1992, et portant sur 8,805 biopsies.

Results of a study conducted by the "cervix cancer group" of PETRI, in Ile-de-France, from May 1990 to May 1992, and based on 8,805 biopsy specimens. In the absence of Cancer Registry in the Ile de France, no reliable data on invasive and preinvasive neoplasia of the cervix are available concerning this area. The aim of this survey, performed between May 15th, 1990 and May 15th, 1992 in 62 laboratories of pathology under the aegis of the Petri Association (Prévention et épidémiologie des tumeurs en Ile-de-France), was to obtain a better knowledge of this pathology, in which one of the major risk factors is the infection of the cervical epithelium by specific types of human papillomavirus. Over the course of these two years, 8,805 biopsy specimens, taken from neoplastic lesions of the cervix, were analyzed. Intra epithelial neoplasia represented more than 90% of the registered lesions. The average age at the time of the diagnosis was 32.4 years for the cases of condyloma, 32.7 years for CIN I, 33.8 years for CIN II, 36.3 years for CIN III, 45.7 years for micro-infiltrative carcinoma and 50.8 years for infiltrative squamous cell carcinoma. The breakdown of the different histological types of lesions is presented for three characteristic age groups (20-25, 30-35, and 60-70 years old). Differences observed in the eight departments belonging to the Ile-de-France are discussed.

[The correction of the vaginal microflora in patients with a papillomavirus infection associated with cervical intraepithelial neoplasia by using the new bacterial preparation Zhlemik]. / Korrektsiia vaginal'noi mikroflory u bol'nykh s papillomavirusnoi infektsiei v assotsiatsii s tservikal'noi intraépitelial'noi neoplaziei s pomoshch'iu novogo bakteriinogo preparata "Zhlemik".

The microbiological study of vaginal microflora in 40 patients of the reproductive age (20-30 years) with papilloma virus infection in association with cervical intraepithelial neoplasia of the uterine neck revealed dysbiotic disturbances in vaginal microflora, manifested by a decrease in the isolation rate and amount of lacto- and bifidobacteria and by excessive growth of opportunistic microorganisms. The 10-day course of corrective therapy with the new bacterial preparation "Zhlemik" was carried out. Group 1 (81 women) received the preparation intravaginally on a tampon, group 2 (19 patients) received the preparation in the form of vaginal suppositories. The results of this treatment were indicative of a high sanative effect of the preparation irrespective of the method of its application. This was demonstrated by the results of the bacteriological study made after bacterial correction: the amount of the Lactobacillus was restored, and they could be isolated from all patients; the level of contamination of the cervicovaginal niche with opportunistic microbial strains considerably decreased. The positive clinical effect after bacterial therapy with "Zhlemik" was observed in 93-95% of cases, depending on the form of its application.

Comparison of women with cervical human papillomavirus infection and genital warts. I. Some behavioural factors and clinical findings.

OBJECTIVE: To determine if behavioural factors, other than sexual, differ between women with cervical human papillomavirus infection (CHPI) and those with genital warts (GW). DESIGN: A structured, personal in-depth interview which included details on sexual behaviour, hygiene, gynaecological complaints, and demographical characteristics and a gynaecological examination which included vaginal culture and human papillomavirus (HPV) typing with Southern blot. SUBJECTS: Women (n = 972) who had attended two family planning clinics and one youth clinic for contraceptive advice. RESULTS: Out of this female population 66 (6.8%) were found to have CHPI, 39 (4.0%) had genital warts (GW), and 30 (3.1%) women reported genital warts within the last two years. The women with CHPI had had significantly less education, were more often immigrants, had a vaginal flora change more frequently and were more often smokers than the women with GW. The women with GW reported lower abdominal pain significantly more often, had a leucocyte dominance in the vaginal secretion more often and favoured bathing in a bathtub more than the women with CHPI. After adjustment for sexual behavioural factors the significant difference between the two groups for bathing in a bathtub and lower abdominal pain remained. CONCLUSION: Although both conditions are caused by HPV, there are behavioural differences between women with CHPI and women with CA.

[The effect of SolcoTrichovac on the vaginal microflora of patients with a papillomavirus infection associated with a cervical intraepithelial neoplasm]. / Izuchenie vliianiia "Solkotrikhovaka" na vaginal'nuiu mikrofloru u bol'nykh s papillomavirusnoi infektsiei v assotsiatsii s tservikal'noi intraépitelial'noi neoplaziei.

The microbiological study of vaginal secretions of 39 female patients of reproductive age (20-30 years) with papilloma virus infection associated with cervical intraepithelial neoplasia (CIN) was carried out. Of these patients, 28 with papilloma virus infection associated with CINI-II made up group I and II having this infection associated with CINII made up group 2. Dysbiotic disturbances in vaginal bacterial flora, found in these patients, were manifested by a decrease in the isolation rate and number of the lacto- and bifidobacteria simultaneously with the excessive growth of opportunistic bacteria. The results of the oral administration of Solco-Trichovac are indicative of the effectiveness of this preparation, which was confirmed by the data of clinical and bacteriological studies. Together with an increase in the isolation rate of lacto- and bifidobacteria, the level of the contamination of the cervicovaginal niche with opportunistic and pathogenic bacterial strains decreased. The results thus obtained make it possible to recommend Solco-Trichovac for the complex treatment of with papilloma virus infection associated with CIN.

Correlación entre variables ginecoobstétricas con lesiones morfológicas por virus del papiloma humano, premalignas y malignas del cérvix uterino / Gyneco-obstetric variables and their correlation with morphological lesions on human papilloma virus, premalignant and malignant lesions of the uterine cervix

Las infecciones en el cérvix uterino y neoplasias intraepiteliales son frecuentes en nuestra población femenina. El objtivo del presente trabajo fue identificar la asociación de neoplasias intraepiteliales del cérvix con alteraciones morfológicas ocasionadas por virus del papiloma humano y definir su correlación con algunas variables ginecoobstétricas. Se seleccionaron 147 casos de 215 con diagnóstico de neoplasias intraepiteliales cerviales efectuando mediante citología cervicovaginal durante el año de 1991. También se revisaron las laminillas de las biopsias correspondientes de cada caso. De los 147 casos, 138 presentaron alteraciones citológicas e histopatológicas de infección por el virus del papiloma humano. El 63 por ciento correspondió a condiloma, el 21 por ciento a displasia más condiloma y el 16 por ciento a carcinoma in situ más condiloma. El tipo de condiloma fue: plano en el 98 por ciento, acuminado en el 1 por ciento y atípico en el 1 por ciento. El promedio de edad de las pacientes fue 36 años y más del 70 por ciento fueron menores de 40 años. El inicio de vida sexual activa antes de los 19 años se asoció con un alto índice de displasia (50 por ciento). En las mujeres que tuvieron el primer parto antes de los 19 años se identificó: condiloma (52 por ciento), displasia (66 por ciento) y carcinoma in situ (50 por ciento); mientras que, en las enfermas con dispositivo intrauterino los porcentajes respectivos para estas lesiones fueron 38, 41 y 35. Se concluye que el mejor control del cáncer cervicouterino en nuestro medio es la prevención a través de examen cervicovaginal, prueba sencilla, útil y de bajo costo. Las campañas de detección oportuna de cáncer cervicouterino deben ocupar un lugar prioritario en las instituciones de salud

Interferon treatment enhances the expression of underphosphorylated (biologically-active) retinoblastoma protein in human papilloma virus-infected cells through the inhibitory TGF beta 1/IFN beta cytokine pathway.

Interferons (IFN) regulate transcription of certain genes playing a role in cell proliferation. Targets of IFN action may include tumor suppressor genes such as the retinoblastoma (RB) gene and cytokines such as transforming growth factor beta 1 (TGF beta 1) and IFN beta which are inhibitors of epithelial cell proliferation. Using reverse transcription followed by PCR amplification, an increase of those growth inhibitory gene mRNA levels (TGF beta 1, IFN beta and RB) were found after interferon treatment in condylomas harboring non-oncogenic human papilloma virus (HPV 6/11) types, in an oncogenic HPV 16-containing cell line, and in a HPV negative, epidermoid carcinoma cell line. In addition, immunodetection by Western blot demonstrated a higher proportion of underphosphorylated (active form) retinoblastoma gene protein (pRB) after IFN treatment due to the decrease in the phosphorylating cdc2 kinase levels. Changes in the phosphorylation pattern of pRB together with the increased expression of those inhibitory genes represent a growth inhibited state in those cells as demonstrated by diminished c-myc expression. Since the extent of c-myc inhibition was significantly lower in the case of oncogenic HPV infection, a role of viral oncoproteins in abrogation of the antiproliferative effect of IFN therapy could be considered. These results demonstrate a new mechanism via which IFNs exert their antiproliferative effect on HPV-infected cells by affecting the expression and phosphorylation of the RB tumor suppressor gene, through the inhibitory TGF beta 1/IFN beta cytokine pathway.

[Diagnosis between condyloma acuminatum and pseudocondyloma in lower female genital tract as determined by a PCR-based method].

From Jan. 1990-Aug. 1992, 616 patients with papillomatous growth of the lower female genital tract (the nodular type 307 cases, the papular type 309 cases) were investigated as determined by a PCR (polymerase chain reaction)-based method, associated with immunohistochemistry avidin biotin complex (ABC), electron microscopy, histopathology, colposcopy and clinical follow-up. The PCR is the most sensitive and specific method. Using PCR the HPV DNA 6.11.16.18.33 were positive in 97.90% of the nodular type. However HPV DNA were positive in 1.10% of the papular type. In the patients with both type, HPV DNA were also positive in nodular, but negative in papular. In the nodular type the HPV-Ag present in 53.55% by ABC method, the koilocytes were 70.49% by microscopy, HPV particles were seen in 5 out of 85 samples by electron microscopy. So that the nodular type (typical cauliflower like) is genital warts (condyloma acuminatum) by HPV infection. The papular type (typical papular or finger like) growth on the mucosal surface of the labia minora of lower vagina. They were negative for HPV DNA, HPV-Ag, HPV particles and koilocytes. On follow-up observation for 3 months to 2 years they had not developed to nodular type and no sexually transmitted feature was observed. The papular type is pseudocondyloma.

Efficient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles.

The L1 genes of two human papillomavirus type 16 (HPV16) isolates derived from condylomata acuminata were used to express the L1 major capsid protein in insect cells via recombinant baculoviruses. Both L1 major capsid proteins self-assembled into virus-like particles (VLP) with high efficiency and could be purified in preparative amounts on density gradients. The yield of VLP was 3 orders of magnitude higher than what has been obtained previously, using L1 derived from the prototype HPV16. DNA sequence comparison identified a single nonconserved amino acid change to be responsible for the inefficient self-assembly of the prototype L1. VLP were also obtained by expressing L1 of HPV6, HPV11, and cottontail rabbit papillomavirus, indicating that L1 from a variety of papillomaviruses has the intrinsic capacity to self-assemble into VLP. Coexpression of HPV16 L1 plus L2 by using a baculovirus double-expression vector also resulted in efficient self-assembly of VLP, and the average particle yield increased about fourfold in comparison to when L1 only was expressed. Coimmunoprecipitation of L1 and L2 and cosedimentation of the two proteins in a sucrose gradient demonstrated that L2 was incorporated into the particles. The ability to generate preparative amounts of HPV16 L1 and L1-L2 VLP may have implications for the development of a serological assay to detect anti-HPV16 virion immune responses to conformational epitopes and for immunoprophylaxis against HPV16 infection.

Human papillomavirus type 6 associated Buschke-Loewenstein tumor (giant condyloma acuminatum).

The term "Buschke-Loewenstein tumor" has been used for tumors with exophytic, wart-like excrescences in the anogenital region. This broadly includes giant condyloma acuminatum and verrucous carcinoma. We report a 44-year-old Japanese man with a giant condyloma acuminatum Buschke-Loewenstein tumor on the right femoinguinal area. The lesion was a huge grape-like nodule composed of multiple small nodules, reaching 135 x 65 x 40 mm in size. Histologically, it showed a regularly acanthotic papilloma with numerous koilocytes in the upper squamous and granular layers. Ultrastructural findings included gradual differentiation from basal cell layers to uppermost corneocytes without disorganized relationships in the epithelial-stromal junction or cellular atypia. Human papillomavirus type 6 DNA was detected in the tumor tissues by polymerase chain reaction and restriction enzyme analysis, although immunohistochemical staining for papillomavirus common antigen was negative.