Human papillomavirus DNA detection in primary anogenital warts and cervical low-grade intraepithelial neoplasias in adults by in situ hybridization.

In this study, 58 consecutive patients with primary anogenital warts were selected from patients attending a genitourinary clinic. Patients were grouped on the basis of clinical lesion site, i.e. patients with genital warts only, patients with perianal or anal canal warts only, and patients with concurrent perianal and genital warts. Of these patients, 38% of the men (12/31) and 33.3% of the women (9/27) had other anogenital infections, such as nonspecific urethritis (NSU) or nonspecific genital infection, which were the most common. Of the patients who had perianal warts, 37% of the men (7/19) and 25% of the women (4/16) also had warts in the anal canal. Of the women who had anogenital warts, 63% (17/27) had concurrent subclinical low-grade cervical intraepithelial neoplasia (CIN) lesions. Human papilloma virus (HPV) DNA (either 6 or 11, 16 or 18, or 31 or 33 or 35) was detected in 53.3% (40/75) of the anogenital wart biopsy samples, and in 35.2% (6/17) of the low-grade CIN lesions. HPV types 6 or 11 were the most common types in anogenital warts (45.3%); and in CIN lesions HPV types 6 or 11 and 16 or 18 were found with equal frequency (17.6% each). There were no significant differences in HPV types between patients with genital warts and patients with perianal and anal canal warts. Anogenital infection with HPV is multicentric; external anogenital warts and subclinical CIN lesions often exist concurrently. The low prevalence of HPV DNA detected in anogenital warts and CIN biopsy samples may be due to insensitivity of the in situ hybridization technique used in this study.     

Human papillomavirus (HPV) viral load and HPV type in the clinical outcome of HIV-positive patients treated with imiquimod for anogenital warts and anal intraepithelial neoplasia

OBJECTIVE: To evaluate the efficacy of 5% imiquimod in HIV-positive male patients with anogenital warts or anal intraepithelial neoplasia (AIN), and to elucidate whether human papillomavirus (HPV) type and viral load were important for clinical outcome and recurrences. METHODS: Thirty-seven patients with histologically proven anogenital warts or AIN were enrolled. Topical 5% imiquimod was applied three times per week for more than 8 h overnight for 16 weeks, although patients were allowed to continue therapy for 4 more weeks if they did not have complete clearance of lesions. RESULTS: Mean age was 34 years. The perianal area was the main lesion location. Thirty-three patients had CD4 counts of < 500 cells/mm(3). Eighteen patients had a histopathological diagnosis of AIN-1. Main HPV types detected corresponded to low-risk HPV types. At 20 weeks of therapy, 46% patients achieved total clearance whereas 14 patients had > 50% clearance. Recurrence was observed in 5 of 17 patients who cleared. Clearance was not influenced by patients' CD4 counts, wart location, HIV viral load or HPV viral load. CONCLUSIONS: The assumption that visible perianal warts are benign lesions in HIV-positive patients has to be reevaluated since an important number of such lesions could correspond to low-grade anal disease, which in turn could progress to high-grade anal disease or cancer. In addition, our results in this preliminary study indicate that imiquimod appears to be effective in treating AIN in HIV-positive patients. Further studies are needed to document its utility to prevent high-grade dysplasia and/or anal cancer.     

Effects of imiquimod on latent human papillomavirus anal infection in HIV-infected patients

INTRODUCTION: High risk human papillomaviruses (HPV) have emerged as risk factors for anal carcinoma particularly in HIV-infected patients who demonstrate a high rate of anal HPV infection. Considering the relationship between the presence of anal infection and the development of neoplastic lesions, we wished to assess the capacity of imiquimod to eradicate latent HPV infection in HIV-infected patients. PATIENTS AND METHODS: We conducted a prospective, randomized, double-blind and vehicle controlled study. Two consecutive anal swabs were taken at 2 month intervals and only patients with two consecutive tests positive for the detection of HPV-DNA (Hybrid Capture II) were included. Patients with persistent latent HPV infection were divided into 2 groups who applied imiquimod versus vehicle during 6 weeks. HPV-DNA presence was then investigated 2 and 4 months following the onset of treatment. RESULTS: Among the 80 HIV-infected patients, 26 (32.5 p. 100) had 2 positive consecutive assays, and 19 patients were included in the study. After randomization, 9 patients received imiquimod and 10 vehicle. There was no significant difference between treatment groups according to the following criteria: gender, route of HIV transmission, CDC stage, prior medical history of sexually transmitted diseases or anogenital warts. 33.3 p. 100 (3/9) of patients treated with imiquimod were negative at M2, whereas 100 p. 100 (10/10) vehicle treated-patients remained positive (p=0.08). Similar results were observed at the M4 visit. DISCUSSION: Our study confirmed the increased prevalence of latent HPV-DNA infection in HIV-infected patients. In spite of the low number of treated patients, we did not observe a statistically significant decrease in HPV-DNA in anal swabs from imiquimod-treated patients as compared to placebo-treated patients.     

Anal human papillomavirus infection: a comparative study of cytology, colposcopy and DNA hybridisation as methods of detection.

OBJECTIVE--To compare anal cytology, colposcopy and DNA hybridisation as methods of detecting anal HPV infection. SUBJECTS AND DESIGN--Patients attending: (1) a genitourinary medicine (GUM) clinic with ano-genital warts; (2) a surgical out-patient department with anal fissure or haemorrhoids were examined for evidence of anal HPV infection. RESULTS--Considering GUM clinic attenders, 17% (38/225) and 40% (90/225) had perianal or anal canal warts respectively. Colposcopic examination revealed anal acetowhite lesions without warts in 28% (63/225). Cytological evidence of HPV infection was found in 98%, 83%, and 90% of patients with anal canal warts, perianal warts and acetowhite lesions respectively. Anal intraepithelial neoplasia (AIN) was documented in 22% of patients with anal canal warts compared with 6% with perianal warts (p less than 0.01). HPV DNA was detected from the anal brushings of 71%, 50%, 32%, and 29% of patients with anal canal warts, perianal warts, acetowhite lesions and a normal anal examination respectively. HPV type 6/11 was detected in the majority of HPV positive samples. Considering surgical out-patient attenders with no history or signs of anal warts, 25% showed cytological evidence of anal HPV infection and HPV DNA was detected from anal brushings in 3% (2/71). CONCLUSION--Anal examination with the colposcope is a useful method for detecting subclinical HPV infection. Anal cytology may prove helpful for detecting AIN, however, since koilocytosis was rarely seen, the specificity of the cytological criteria for anal HPV infection in the absence of AIN is uncertain. DNA analysis of anal brushings proved only moderately sensitive.     

浙江丽水地区男性肛门生殖器疣患者人乳头瘤病毒基因型研究

【摘要】 目的 了解浙江丽水地区男性肛门生殖器疣患者感染人乳头瘤病毒（HPV）基因型的分布状况。方法 PCR-反向斑点杂交技术对150例男性肛门生殖器疣患者标本进行HPV基因分型,包括3种低危型HPV-6、11、43和16种中高危型HPV-16、18、31、33、35、39、45、51、52、53、56、58、59、66、68、CP8304。 结果 150例男性肛门生殖器疣患者中91例（60.67%）检出HPV,其中有74例（81.32%）为低危型HPV-6、11、43的单一或多重感染,另有17例（18.68%）为中高危型的单一或多重感染。31例（34.07%）为多重感染（包括2 ～ 5种基因型混合感染）,其中低危型合并中高危型的多重感染20例占64.52%,低危型之间的二重感染6例占19.35%;HPV-6、11合并中高危型感染分别为13例（41.94%）和6例（19.35%）。各HPV基因型感染136例,感染率从高到低依次为：HPV-6（39例,28.68%）、11（36例,26.47%）、16（11例,8.09%）、52（7例,5.15%）、53（7例,5.15%）、51（6例,4.41%）、58（6例,4.41%）和43（6例,4.41%）。 结论 男性生殖器疣患者HPV基因型感染中,低危型HPV感染占绝对优势,多重感染及各基因型的分布状况差异较大。     

Imiquimod 5% cream for external genital or perianal warts in human immunodeficiency virus-positive patients treated with highly active antiretroviral therapy: an open-label, noncomparative study

Background  Human immunodeficiency virus (HIV)+ patients have an increased risk of anogenital warts. High-risk (HR) human papillomaviruses (HPVs), especially types 16 and 18, are major risk factors for precancerous and cancerous lesions of the anogenital tract, while low-risk (LR) HPVs are associated with benign lesions. Cure of genital warts with ablative techniques, surgical excision, podophyllotoxin or trichloroacetic acid is frequently difficult. Treatment with imiquimod cream showed a total clearance of external genital or perianal warts in about 50% of immunocompetent subjects. However, total clearance was reduced in HIV+ subjects not treated with highly active antiretroviral therapy (HAART).
Objectives  To assess clinically and by monitoring HPV content the efficacy of 5% topical imiquimod to treat anogenital warts in HIV+ subjects with at least partially restored immune functions.
Methods  Fifty HIV+ patients successfully treated with HAART (total CD4+ cells ≥ 200 cells mm⁻³ and plasma HIV RNA load < 10⁴ copies mL⁻¹) with anogenital warts were included. Imiquimod 5% cream was applied on external genital or perianal warts three times weekly for up to 16 weeks. Warts were tested at entry and after treatment for human LR- and HR-HPV DNA.
Results  Total wart clearance was observed in 16 of 50 (32%) patients at week 16. At enrolment, HPV DNA was present in more than 90% of lesions with a majority of lesions co-infected by HR- and LR-HPV. At study end, the HPV load decreased or became undetectable in 40% of cases studied.
Conclusions  Imiquimod 5% cream did not show safety concerns and is suitable for use in HIV+ subjects with anogenital warts and successful HAART treatment.     

Genotype distribution of human papillomavirus in anogenital warts of male patients in Taiwan

BackgroundReports on the prevalence of different human papillomavirus (HPV) genotypes in male patients with anogenital HPV infection are limited.MethodsWe retrospectively analyzed the HPV genotypes of 100 consecutive patients seen in our department with anogenital HPV infection during 2003–2006. History was gathered from the medical records.ResultsThe most common HPV genotypes among Taiwanese male patients for check of anogenital warts (in descending order) were HPV 6 (46%), HPV 11 (28%), HPV 16 (6%), HPV 33 (5%), HPV 66 (5%), HPV 18 (4%), HPV 53 (4%), and HPV 72 (4%). Coinfections with two, three, and four genotypes of HPV were present in 16%, 7%, and 1% of the patients, respectively. HPV 16 or 18 was found in 10% of cases, with 60% (6/10) coexisting with HPV 6/11. The presence of either HPV 6, 11, 16, or 18 was 77%. HPV 16 was more common in anal compared to genital warts, with an odds ratio of 3.65.ConclusionThe most common genotype of anogenital HPV infection in Taiwanese males was HPV 6, followed by HPV 11. Coinfection with more than one genotype of HPV as well as concurrent low- and high-risk HPV infection was not uncommon.     

Comparison of clinical, histological, and virological symptoms of HPV in HIV-1 infected men and immunocompetent subjects

OBJECTIVE: We assessed the clinical, histological, and virological features of anogenital human papillomavirus (HPV) infection, according to their immune status in HIV-1 infected men, referred for an anogenital examination or treatment, in comparison with immunocompetent patients. METHODS: The study population comprised 33 HIV-1 infected heterosexual or homosexual men and 38 HIV negative men seen in a screening and treatment centre for anogenital HPV infections. All patients were examined with a colposcope. Biopsies were carried out on all subjects with anogenital lesions for histological studies and HPV detection by Southern blot. RESULTS: The HIV infected patients had a balanopreputial HPV infection in 70%, anal in 30%, and urethral in 37%, while HIV negative patients had balanopreputial lesion in 72%, anal in 26%, and urethral in 16%. Diffuse anogenital lesions were present in 33% of the HIV infected cases and in 10.5% of HIV negative cases (p < 0.02). Among the HIV infected patients, the genital HPV lesions were condylomatous in 67.5% of the cases and dysplastic in 57%. HIV negative patients had condylomatous lesions in 86% of the cases and dysplasic in 14%. The condylomatous lesions of HIV infected patients had a low grade malignant histological aspect in 36% of the cases and high grade histological criteria were found in 22% of the dysplasias. Oncogenic HPVs were detected more frequently in HIV infected patients (35% v 12%) and more than one HPV type was found in 21.5% of cases. Neither the anogenital diffusion of the HPV lesions nor their morphological, histological, and virological features differed significantly in patient with CD4 cell counts > or < 200 x 10(6)/l. In contrast, patients with CD4 cell counts < 50 x 10(6)/l had a higher risk of several types of HPVs and of developing a diffuse anogenital infection. CONCLUSION: HIV-1 infected patients had an increased frequency of high grade anogenital dysplastic lesions and a higher frequency of HPV infection with multiple and diffuse sites of involvement. These characteristics of HPV infection were independent of the patients' immune status up to CD4 cell counts > 50 x 10(6)/l but showed an increased risk when the CD4 cell count was < 50 x 10(6)/l. The higher frequency of diffuse anogenital infections among HIV infected men calls for rapid treatment, laser or surgery, given the association of histological features of intraepithelial neoplasia and the presence of multiple HPV infection sites which may be the consequence of immune disturbances, most of which are transmissible potentially oncogenic HPVs.


     

An overview of human papillomavirus infection for the dermatologist: disease,diagnosis, management,and prevention

Genital human papillomavirus (HPV) is a common, usually transient, dermatologic infection transmitted by genital contact that can cause a variety of anogenital diseases, including warts (condyloma), dysplasia (cervical, vaginal, vulvar, anal), and squamous cell carcinoma. A number of treatment modalities are available to treat anogenital warts, both patient‐ and provider‐applied. Treatment is efficacious, but lesions can recur. Bivalent and quadrivalent vaccines are approved to prevent HPV infection. Both are indicated to prevent cervical cancer, while the quadrivalent vaccine is also approved to prevent vaginal/vulvar cancers as well as genital warts in males and females. Providers should clearly explain the natural history and potential sequelae of HPV disease, counsel patients on prevention strategies, and recommend vaccination as an effective method of prevention to their patients.     

Detection of high-risk human papillomavirus type 16/18 in cutaneous warts in immunocompetent patients, using polymerase chain reaction

Cutaneous warts are caused by human papillomavirus (HPV). Prevalence studies of the types of HPV present in cutaneous warts have been carried out more frequently in immunosuppressed patients. The present study was designed to study the association of high-risk HPV in cutaneous warts of immunocompetent patients. A total of 45 cases of cutaneous warts from various sites in immunocompetent subjects were analyzed for HPV. Samples included both archival material i.e., paraffin embedded and fresh tissue. Highly sensitive and comprehensive polymerase chain reaction (PCR) methodology for detection of HPV of high oncogenic potential, HPV 16/18, was employed. Human papillomavirus 16 was detected in 3 (6.6%) patients. None of the lesions demonstrated HPV 18. None of the cutaneous warts demonstrated histopathological features associated with dysplasia or neoplasia. The identification of HPV 16 in cutaneous warts, which are benign proliferations of the skin, further expands the spectrum of HPV-linked lesions. It remains of critical interest to determine whether these types are specifically associated with the development of malignant lesions analogous to those seen in anogenital cancer.     

Subcutaneous interferon alpha 2a combined with cryotherapy vs cryotherapy alone in the treatment of primary anogenital warts: a randomised observer blind placebo controlled study.

OBJECTIVE--To compare patient tolerance and treatment efficacy of subcutaneous interferon (IFN) alpha 2a plus cryotherapy versus cryotherapy alone in treatment of primary anogenital (AG) warts. DESIGN--Randomised placebo controlled observer blind study. Statistical analysis was by chi square and Mann Whitney U tests. PATIENTS--60 patients with newly diagnosed AG warts. INTERVENTION--29 and 31 patients were treated with subcutaneous IFN alpha 2a plus cryotherapy or placebo injections plus cryotherapy, respectively. MAIN OUTCOME MEASURES--Clinical presence or absence of AG warts. Patients wart-free at 8 weeks were asked to re-attend at 12 weeks; those with persistent warts at 8 weeks were withdrawn from the study. RESULTS--At 8 weeks 60.7% (17/28 patients) of the IFN group and 67.9% (19/28 patients) of the placebo group were clinically wart-free (not significant); corresponding figures at 12 week review were 29.6% (8/27 patients) and 40% (10/25 patients) respectively (not significant). There was no difference in treatment response between males and females. Recurrence of warts at three month review, in patients cleared of warts at 8 weeks, was seen in 50% (8/16) and 37.5% (6/16) of patients in the IFN and placebo groups respectively (not significant). Multiple warts and the presence of perianal/anal canal warts, either alone or concurrent with warts on the genitalia, at first clinic attendance, were adverse prognostic indicators (p less than 0.001, and p = 0.05 respectively). Cervical human papilloma virus (HPV) infection, exophytic or subclinical, was present in 58.3% and 77.2% of females in the IFN and placebo groups respectively, at trial entry. Although these lesions were not directly treated, colposcopic resolution was seen in 12.5% of affected women, in both treatment groups, by the end of the 7 week treatment period. Systemic side effects were significantly more common in the IFN than in the placebo group, 50% versus 10.7% of patients (p less than 0.01). Severe influenza like symptoms occurred, after the first three injections only, in one patient treated with IFN; all other reported side effects were mild. CONCLUSIONS--Subcutaneous IFN alpha 2a combined with cryotherapy is no more effective than cryotherapy alone in the treatment of primary AG warts. The presence of multiple warts and perianal/anal canal warts are adverse prognostic indicators.     

Changes in HPV infection in patients with anogenital warts and their partners.

OBJECTIVES--To investigate the relationship between clinical findings and the detection of human papillomavirus (HPV) DNA in a range of anatomical sites in patients with and without anogenital warts. SUBJECTS--Men and women with a clinical diagnosis of anogenital warts, or a current partner with anogenital warts. SETTING--A department of genitourinary medicine in central London. METHODS--The anogenital areas of the patients were thoroughly examined using a colposcope before and after application of acetic acid. Different types of specimens were taken from a variety of anatomical sites. Superficial skin sampling was performed by the application of slides covered with "Superglue" (SG) to clinically normal and abnormal areas of anogenital skin. The presence of human cells in the SG samples was confirmed by detection of the beta-globin gene using the polymerase chain reaction (PCR). HPV DNA was extracted from the specimens and amplified by using consensus primers with the PCR. HPV types 6, 11, 16, 18, 31 and 33 were identified by Southern blotting followed by hybridisation. RESULTS--In women, HPV DNA was detected in 83% of wart biopsies, 29% of cervical biopsies, 36% of cervical scrapes, 25% of urethral loop specimens, 37% of vaginal washes and 33% of rectal swab specimens. In men, HPV DNA was detected in 67% of wart biopsies, 37% of urethral loop specimens and 12% of rectal swab specimens. Of the SG samples containing the beta-globin gene, 49% from women and 50% from men contained HPV DNA. HPV DNA was not detected in buccal scrapes and serum samples from women or men. Of all specimens with detectable HPV DNA, there was evidence of a single HPV type in 41%, multiple types in 48% and undetermined types in 11%. Samples taken from different sites of a patient tended to have HPV types in common. Sexual partners, however, did not consistently have HPV types in common. CONCLUSIONS--HPV DNA was distributed widely in the anogenital area, in warts, acetowhite areas and clinically normal skin. The SG technique was well tolerated by patients and produced results consistent with other findings. Sampling from a single site of the genitalia on one occasion may significantly underestimate the infection rate with HPV. Multifocal infection of the anogenital area with HPV should be taken into consideration when interpreting epidemiological studies and management strategies.     

Human papilloma virus vaccines: Current scenario

Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection with an estimated worldwide prevalence of 9-13% and approximately 6 million people being infected each year. Mostly acquired during adolescence or young adulthood, HPV presents clinically as anogenital warts and may progress to precancerous lesions and cancers of the cervix, vagina, vulva, penis and anus, and oropharynx. HPV infection is considered to contribute to almost 100% cervical cancers and at least 80% of anal and 40-60% of vulvar, vaginal, and penile cancers. At present, two prophylactic HPV vaccines are commercially available and both are prepared from purified L1 structural proteins. These proteins self-assemble to form virus-like particles that induce a protective immunity. Gardasil(?) is a quadrivalent vaccine against HPV types 6, 11, 16, and 18 and is recommended for use in females 9-26 years of age, for the prevention of cervical, vulvar, and vaginal cancers and intraepithelial neoplasia and condyloma acuminata and recently for vaccination in boys and men 9-26 years of age for the prevention of genital warts. Cervarix? is a bivalent vaccine approved for the prevention of cervical cancer and precancerous lesions caused by HPV 16 and 18, in females 10-25 years. HPV vaccines are safe and efficacious against type-specific HPV-induced anogenital warts, precancerous lesions, and cervical cancer. The vaccines are most effective when given before the onset of sexual activity and provide long-term protection. Effective vaccination coverage in young adolescent females will substantially reduce the incidence of these anogenital malignancy-related morbidity and mortality. There is need to generate India-specific data on HPV epidemiology and HPV vaccination efficacy as well as continue worldwide surveillance and development of newer vaccines.     

A morphologic, pathologic, and virologic study of anogenital warts in men.

BACKGROUND AND DESIGN--Infection with human papillomavirus (HPV) in the anogenital region is associated with benign papillomas (condyloma acuminatum), subtle verrucous changes, subclinical infection, and malignant lesions. Although both men and women are affected, much of the investigation has been directed toward women in the study of cervical and vulvar carcinoma. The current investigation focuses on HPV infection in men. This study was undertaken to correlate the clinical spectrum of disease in our population of male patients with histopathologic features, immunoperoxidase staining for viral capsid antigen, and viral typing. Genital lesions from 26 patients were examined and tested prospectively over a 1-year period. RESULTS--The 26 lesions examined demonstrated variable morphologic features with regard to location, size, surface characteristics, and color. Histopathologic features were consistent with the diagnosis of venereal warts, but not necessarily diagnostic. Three of five standard histopathologic criteria were present in only 71% of the specimens. Despite the morphologic variability and the indeterminant histopathologic findings, 20 of 23 lesions positive for the genital tract HPV types tested contained HPV types 6 and/or 11. CONCLUSIONS--We conclude that the morphologic appearance of anogenital warts does not necessarily correlate with HPV type. Histopathologic study is helpful in excluding other diagnoses but may be indeterminant in the diagnosis of venereal warts. All men with anogenital warts should be counseled, treated, and undergo follow-up regardless of HPV type.     

Successful treatment of anogenital Bowen's disease with the immunomodulator imiquimod,and monitoring of therapy by DNA image cytometry

Imiquimod (Aldara, 3M) is an immune response modifier used for the treatment of anogenital warts. We report a 55-year-old non-immunocompromised woman with extensive, human papillomavirus (HPV) 16-positive anogenital Bowen's disease. After 5 months of local treatment with imiquimod, the lesions completely regressed clinically and histologically, and HPV 16 DNA was no longer detectable. Moreover, DNA image cytometry revealed DNA aneuploidy (an indicator of prospective malignancy) in pretreatment samples but not in post-treatment samples. Therefore, imiquimod might be a treatment option for Bowen's disease, particularly in patients where other treatment modalities such as surgery are contraindicated.     

Anal human papillomavirus DNA screening by Hybrid Capture II in human immunodeficiency virus-positive patients with or without anal intercourse

High risk human papillomaviruses (HPVs) have emerged as risk factors for anal carcinoma, of which incidence is higher in HIV-positive patients than in the general population. The aim of our study was to investigate the prevalence and risk factors for anal HPV infections in HIV-positive patients with or without history of anal intercourse. Fifty HIV 1-infected patients (36 men and 14 women) were tested at entry and followed-up every 3 months for one year for the presence of anal HPV DNA by the Hybrid Capture II trade mark assay. A series of 50 HIV-negative subjects matched for age and sex served as controls. At enrollment, anal HPV DNA was present in 29/50 HIV-positive patients (58 %) and in 3/50 control subjects (6 %). High risk (HR) HPV genotypes were detected in 20/50 HIV-positive patients (40 %) with no difference in homosexual men and other HIV-positive patients. Risk factors for HPV infection were CD4 + cell counts less than 500/microL (RR: 2.13 [95 % CI: 1.0-4.7]) and history of anogenital warts (RR: 2.36 [95 % CI: 1.2-4.6]). The HPV load was higher in patients with CD4+ < or = 500/microL than in patients with CD4 + > 500/microL (p < 0.04). During the follow-up, anal HR HPV DNA was repeatedly identified at high levels in 5 HIV-positive patients. There is some convincing evidence that HIV-positive patients with low CD4+ cells, whatever the routes of HIV transmission, have a high rate of anal HPV infection and might be at increased risk of developing anal neoplastic lesions. Identifying HR HPV infection might be warranted in immunosuppressed patients.     

Anal condylomas in men. 1. Histopathological and virological assessment.

A series of 128 biopsy specimens from anal condylomas in 73 homosexual or bisexual and 38 heterosexual men (mean (SD) age 31.8 (9.6) years) were subjected to histological assessment and human papillomavirus (HPV) typing by in situ DNA hybridisation with 35S-labelled HPV 6, 11, 16, 18, 31, and 33 probes. Most patients were also tested serologically for antibodies to human immunodeficiency virus (HIV). As evaluated on light microscopy, most (74%, 95/128) of the lesions were exophytic (papillary) acuminate warts, 15% (19) were flat, and 11% (14) were pigmented papulous lesions. No signs of anal intraepithelial neoplasia (AIN) were seen in 70% (90) of the 128 biopsy specimens (NAIN), 27% (35) were classified as showing AIN I, and another 2% (three) as AIN II. AIN was significantly (p less than 0.05) more often associated with papulous lesions, only 43% (6/14) of which showed NAIN compared with 72% (68/98) of acuminate condylomas. The duration of disease was directly related to the presence and severity of AIN in the lesions; thus in 47 lesions that had been present for more than 12 months, NAIN was found in 31 (66%), AIN I in 14 (30%), and AIN II in two (4%). HPV DNA of at least one of the six types tested for was detected in 109/125 (87%) lesions. HPV 6 and HPV 11 were the two most common types, comprising 57% (62) and 37% (40), respectively, of the 109 HPV DNA positive cases. Only seven (6%) biopsy specimens were associated with any of HPV types 16, 18, 31, or 33, which carry a high risk of potential malignant transformation. No association was found between sexual preferences of patients and the incidence of any of the various HPV types. Neither did the distribution of the various HPV types differ between men with antibody to HIV and those without antibody. All the men with antibody to HIV were homosexual or bisexual. On microscopy, 93% (38) of 41 lesions containing HPV 11 and 75% (48/64) of HPV 6 lesions were of the acuminate wart type; in comparison, the remaining 16 HPV 6 lesions were equally either flat or papulous (eight, 13% each). Of the 64 HPV 6 and 41 HPV 11 associated lesions, 73% (47) and 63% (26), respectively, were classified as NAIN. Only two lesions were associated with HPV 16, and both showed mild dysplasia. On the other hand, two HPV 6 induced lesions were associated with AIN II. No differences were found between HPV 6 and HPV 11 in duration of disease; (39%, and 27% respectively, had been present for more than 12 months). The results showed that overt anal wart disease was associated with HPV types 6 and 11 in most cases. Although HPV types considered as being of higher oncogenic potential were detected relatively rarely, the associated AIN in a relatively high proportion (31% 32/105) of HPV 6 or 11 induced lesions indicated that a malignant potential, even for HPV 11 associated anal warts, cannot be excluded.     

Detection of human papillomavirus DNA in anogenital condylomata in men using in situ DNA hybridisation applied to paraffin sections.

An in situ DNA hybridisation method was used to detect human papillomavirus (HPV) DNA (HPV types 6, 11, 16, and 18), and an immunoperoxidase (IP-PAP) method to detect HPV structural protein expression in paraffin sections of biopsy specimens from 133 men treated for penile (in 114 cases) and anal (in 19 cases) warts. The anatomical distribution on the penis of classic condyloma acuminatum and of papular and flat condylomata was practically identical. The gross appearance of the warts did not correlate with their morphology on light microscopy. The detection rate of dysplasia was very different in the three types of lesions (25% in flat, 50% in acuminatum, and 75% in papular warts). Of 133 lesions, 59 (44.4%) contained HPV antigens, their expression being inversely related to the grade of dysplasia; only 17% of HPV 16 lesions had detectable HPV antigen compared with 50% to 67% in lesions of the other three HPV types. HPV 16 and HPV 18 DNA were most commonly (11%) detectable in Bowenoid lesions; however, most of the HPV 16 and 18 positive cases were found among the flat and acuminatum type of lesions. Though the overall detection rate of HPV DNA (76%) did not correlate with the grade of dysplasia, a clear cut association of HPV 16 and HPV 18 with dysplastic lesions was found, none of the HPV 16 and 25% of the HPV 18 positive cases being devoid of concomitant dysplasia. The corresponding figures for HPV 6 and HPV 11 were 59.2% and 68.8%, respectively. The implications of these findings are discussed in terms of epidemiologically established connections between penile and cervical cancer, with special emphasis of the high risk HPV types 16 and 18. The applicability of in situ DNA hybridisation as a powerful tool in the analysis of specific HPV DNA sequences in routinely processed biopsy specimens from these lesions is emphasised.     

Genital warts

Genital warts are an epidermal manifestation attributed to the epidermotropic human papillomavirus (HPV). Over 100 types of double-stranded HPV have been isolated and completely sequenced thus far. HPV are grouped into low-risk (non-oncogenic) types such as type 6 and type 11, which cause benign anogenital warts (condyloma accuminata), and high-risk (oncogenic) types, such as types 16, 18, 31, and 45, which occasionally lead to cancer.     

Perianal Bowen's disease associated with anorectal warts: a case report

The occurrence of anogenital warts has increased both in clinic and in private practice. Both sexes and all races are affected, with the highest prevalence in patients aged 15 to 40 years. The etiologic agent, the human papillomavirus (HPV), has been classified by DNA hybridization techniques into at least 42 types, of which types 16 and 18 are considered to carry a high risk for cancer. A patient who had been seen intermittently over a period of 26 years with perianal and anal warts that responded to treatment finally developed two granulomatous nodules morphologically different from the previous lesions. A biopsy confirmed that the nodules were typical of Bowen's disease, a precancerous lesion, and they were surgically excised. Thus, anogenital warts that fail to respond to conventional therapy or change in appearance warrant a biopsy and, where the technique is available, DNA typing to identify the viral pathogen.