Detection of human papillomavirus in verrucous carcinoma from HIV-seropositive patients

Anogenital squamous cell carcinoma has been noted with increased frequency in HIV-seropositive patients. Verrucous carcinoma is a variant of squamous cell carcinoma that tends to be locally invasive and non-metastasizing. Although human papilloma-virus (HPV) has been strongly implicated in other squamous neoplasms, it has been variably associated with verrucous carcinoma and has not been examined in these lesions in the HIV-positive population. The aim of this study was to examine the association of HPV with anal verrucous carcinoma in patients with the human immunodeficiency virus (HIV). HPV DNA in situ hybridization for HPV Types 6/11, 16/18, and 31/33/35 was performed on formalin-fixed, paraffin-embedded tissue from six cases of verrucous carcinoma and four cases of condyloma acuminatum in perianal specimens from HIV-seropositive patients. HPV DNA sequences were identified in five of six cases of verrucous carcinoma and in all cases of condyloma acuminatum. Of the five verrucous carcinomas that harbored detectable HPV DNA, four contained HPV 6/11 and two contained HPV 16/18. One contained both HPV 6/11 and HPV 16/18. All four cases of condyloma acuminatum were positive for HPV 6/11. One patient included in this series had three chronologically separate verrucous carcinomas. The initial lesion was negative for HPV DNA. Subsequent verrucous carcinomas were positive for HPV type 6/11 and type 16/18, respectively. The data presented support the concept that verrucous carcinoma in the HIV-seropositive population is associated with HPV, which may indeed play an important role in its pathogenesis.     

Anal cytological abnormalities and anal HPV infection in men with Centers for Disease Control group IV HIV disease.

OBJECTIVE: To characterise risk factors for abnormal and cytology and anal human papilloma virus (HPV) infection in homosexual/bisexual men with advanced HIV related immunosuppression. DESIGN: Cross sectional study of men with Centers for Disease Control group IV HIV disease. SETTING: The University of California San Francisco, AIDS Clinic. PATIENTS: 129 homosexual or bisexual men with group IV HIV disease. METHODS: A questionnaire was administered detailing tobacco, alcohol and recreational drug use, medical history, and sexual practices. Anal swabs for cytology and HPV studies were obtained, as was blood for CD4 levels. MAIN OUTCOME MEASURES: Abnormal anal cytology and anal HPV infection. RESULTS: Abnormal anal cytology was detected in 39% of subjects and anal HPV infection in 93% as measured by polymerase chain reaction (PCR). Risk factors for abnormal cytology in multivariate analysis included HPV 16/18 infection (measured by PCR, RR = 2.1, 95% CI = 1.2-3.5) and intravenous drug use (RR = 1.8, 95% CI = 1.2-2.7). Infection with HPV 6/11 also had significantly elevated RRs in a separate model. Cigarette smoking, alcohol use, recreational drug use, and low CD4 level were associated with abnormal anal cytology in univariate analysis, as was infection with multiple HPV types and high levels of hybrid capture group B viral DNA. CONCLUSIONS: Anal cytological abnormalities and HPV infection are common among homosexual/bisexual men with group IV HIV disease. In this study population, the main risk factors for abnormal cytology were HPV infection and intravenous drug use.     

High prevalence of anal squamous intraepithelial lesions in HIV-positive men despite the use of highly active antiretroviral therapy

BACKGROUND: The impact of highly active antiretroviral therapy (HAART) on the natural history of HPV infection and anal squamous intraepithelial lesions (SIL) in HIV-infected men who have sex with men (MSM) is poorly documented.GOAL The goal of this study was to evaluate the prevalence of anal HPV infection and SIL inpatients under HAART. STUDY DESIGN: Forty-five HIV-infected protease inhibitor-experienced MSM were enrolled in a cross-sectional study. Each patient provided anal samples for anal cytology, histology, and human papillomavirus (HPV) DNA testing. RESULTS: The patients had previously received HAART for a median of 32 months. Anal cytology was abnormal in 32 of 45 (71%) patients, including high-grade SIL in 10 patients (22%), low-grade SIL in 19 patients (42%), and atypical squamous cells of undetermined significance in 3 patients (7%). HPV DNA was detected 36/45 men (80%). The prevalence of anal SIL and HPV infection were similar in patients exhibiting a significant increase in CD4+ cell count after HAART initiation compared with those who did not. CONCLUSION: Our results demonstrate a high prevalence of anal SIL, including high-grade SIL, and anal HPV infection in HIV-infected MSM despite immune restoration under HAART.     

Human papillomavirus-associated increase in p16INK4A expression in penile lichen sclerosus and squamous cell carcinoma.

BACKGROUND: Human papillomaviruses (HPVs) are sexually transmitted human carcinogens that may play a role in the oncogenesis of penile cancer. OBJECTIVES: To investigate the role of HPV infection and expression of the tumour suppressor protein p16INK4A in the pathogenesis of penile cancer. METHODS: By means of polymerase chain reaction amplification and reverse hybridization line probe assay to detect HPV infection, and immunohistochemical staining for p16INK4A and Ki67, we analysed 26 penile squamous cell carcinomas (SCCs) and 20 independent penile lichen sclerosus (LS) lesions from 46 patients. RESULTS: HPV DNA was found in 54% of penile SCCs and 33% of penile LS cases in single and multiple infections. High-risk HPV 16 was the predominant HPV type detected. No relationship between Ki67 expression and HPV infection was observed. Strong immunostaining for p16INK4A correlated with HPV 16/18 infection in both penile LS and penile SCC. In our penile SCC series the cancer margins were also associated with penile LS in 13 of 26 lesions, and HPV was detected in seven of the 13 SCC cases associated with LS and in six of the 11 SCC lesions not involving LS. CONCLUSIONS: Our study shows a high prevalence of HPV 16 and p16INK4A expression in penile lesions, consistent with an active role for HPV in interfering with the retinoblastoma pathway. High-risk HPV infection could be involved in the tumorigenic process in 50% of penile cancers, and the use of prophylactic HPV vaccines has the potential to prevent these cancers.     

Anal carcinoma in human immunodeficiency virus‐positive men: results of a prospective study from Germany

Background Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)‐associated potential precursor lesion of anal cancer, is frequent among human immunodeficiency virus (HIV)‐positive men who have sex with men (MSM). There is a paucity of data published on the progression of high‐grade AIN to invasive cancer as well as on clinical and virological characteristics comparing anal margin and anal canal carcinoma. Objectives To search for anal carcinoma and AIN in a large series of HIV‐positive MSM, to assess treatment response of anal carcinoma, and to analyse lesional HPV spectrum of anal cancers. Methods Detection of anal carcinoma and AIN was performed using cytology, high‐resolution anoscopy, and histology in case of abnormal findings. Additionally, HPV analyses for 36 high‐ and low‐risk α‐HPV types were performed in patients with anal carcinoma. Results In total, 446 German HIV‐positive MSM were examined within an observation period of 5 years and 10 months. Of these, 116 (26·0%) patients had normal findings, 163 (36·5%) had low‐grade AIN, 156 (35·0%) had high‐grade AIN, and 11 (2·5%) had anal carcinoma as evidenced by the highest grade of cytology/histology. Five patients with anal cancer, who had refused treatment of their precancerous lesions, had progressed from high‐grade AIN to invasive cancer within a median time of 8·6 months. All anal cancers carried high‐risk α‐HPV types. All five squamous cell carcinomas (SCCs) of the anal canal were HPV16 positive. In contrast, only one of the four anal margin SCCs were HPV16 positive (HPV31, HPV33 and HPV33 + HPV68 were found in the other three anal margin SCCs). HPV59 was found in two adenocarcinomas, one of which additionally carried HPV33. In contrast to the cancer biopsies, a broad spectrum of surface high‐ and low‐risk HPV types was found in anal swabs of the patients. Surgical excision resulted in long‐term disease control of all anal margin carcinomas, whereas combined chemoradiotherapy in carcinomas of the anal canal was associated with high recurrence rates, high toxicity, and high mortality. Conclusions Anal carcinoma and AIN are frequent in HIV‐positive men, even in patients participating in anal cancer prevention programmes. High‐grade dysplasia in these patients can progress to invasive cancer within a short period of time. Anal margin carcinoma and anal canal carcinoma differ substantially in their lesional HPV spectrum, prognosis and treatment response.     

Papillomavirus-induced anogenital lesions in 121 HIV seropositive men. Clinical, histological, viral study, and evolution]

OBJECTIVE: To determine the prevalence of the Human Papillomavirus (HPV) in Human Immunodeficiency Virus (HIV) infected men, using clinical examination and molecular hybridization in situ. PATIENTS AND METHODS: From May 1995 to May 1997 we studied the prevalence, clinical and histological characteristics, the types and the evolution of the HPV lesions among 121 HIV-infected men. The HPV DNA was determined by molecular hybridization in situ, using biotinylated probes which recognized HPV types 6/11, 16/18 and 31/33/35 in 79 p. 100 (5/19) of the patients (17 biopsies). RESULTS: Sixteen per cent (19/121) of the patients are HPV infected: genital warts in 37 p. 100 (7/19), anal warts in 37 p. 100 (7/19), and ano-genital warts in 26 p. 100 (5/19) of the patients. In every case of anal codyloma, intracanalar lesions were found. In 47 p. 100 (9/19) of the cases, histological exam showed an intra-epithelial neoplasia. The HPV types 6/11, 16/18 and 31/33/51 were positive in 53 p. 100 (9/17), 35 p. 100 (6/17) and 35 p. 100 (6/17) biopsies respectively. High-risk types of HPV have been noted in 71 p. 100 (12/17) of the biopsies. The evolution of the clinical lesions was: recovering in 47 p. 100 (9/19) of the patients (after 3 months of treatment), recurrence in 16 p. 100 (3/19) of the anal warts (after 1 to 3 months of treatment), stabilization in 16 p. 100 (3/19) of the genital warts (after 6 months of treatment) and extension in 11 p. 100 (2/19) of the anogenital warts (after 3 months of treatment). CONCLUSION: The high prevalence of condyloma and dysplasia emphasizes the importance of the anogenital exam in HIV-positive patients. In case of anal lesions, anuscopy and biopsy are required. We insist on the need to closely follow these patients with HPV lesions in order to adapt treatment. Anal cytology and HPV-DNA detection by Hybrid Capture Assay, should be developed for screening and prevention of the malignant transformation of HPV lesions in this population.     

Anale intraepitheliale Neoplasie und Analkarzinom

Anal dysplasia is common in HIV patients, especially in HIV-positive men having sex with men (MSM). High-grade anal dysplasia can progress to invasive anal cancer. As in cervical carcinoma, there is a cause and effect relationship between anal cancer and human papillomavirus (HPV) infection, especially with high-risk types such as HPV16. Several experts have recommended screening programs for anal cancer, including anal cytology along the lines of the Pap smear in women. Such screenings should only be performed if pathological findings result in further diagnostic steps and, if necessary, appropriate treatment. Clinical inspection, lesion biopsy, and treatment of anal dysplasia are performed under high-resolution anoscopy. Anal cancer is divided into cancer of the anal margin and cancer of the anal canal. This classification is important because of the difference in treatment regimens. Early cancer of the anal margin is excised akin to squamous cell cancer of the exposed skin, whereas cancer of the anal canal is treated by radiochemotherapy. HIV-positive and HIV-negative patients have similar response rates to combined radiochemotherapy. However, side effects, especially acute post-irradiation skin toxicity, early local recurrences, and abdominoperineal rectal excision are more common in HIV-positive patients. Physicians working in the field of HIV/AIDS should regularly screen their patients for the presence of anal dysplasia and anal cancer. Basic diagnostic workup includes clinical inspection of the perianal area, digital rectal examination, and anal cytology.     

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.     

Anal intraepithelial neoplasia in HIV infection

Human papillomavirus (HPV) infections belong to the most common sexually transmitted infections worldwide. While the immune system eliminates most HPV infections over time in immunocompetent individuals, HPV infections tend to persist in immunodeficient individuals. In HIV‐infected men who have sex with men (MSM), anal HPV prevalence is more than 90% and infections with multiple HPV types are common. Consequently, HPV‐associated anogenital malignancies occur with high frequency in patients with HIV infection. Anal intraepithelial neoplasia (AIN) is a potential precursor lesion of squamous cell carcinoma of the anus. Like its cervical counterpart, cervical intraepithelial neoplasia (CIN), AIN is causally linked to persistent infections with high‐risk HPV types such as HPV16 or HPV18. As AIN and CIN share distinct biological similar‐ities, AIN screenings analogous to Pap smear programs for CIN have been recommended in high‐risk populations to reduce the incidence of anal carcinoma. These screenings include cytological analysis followed by high resolution anoscopy in case of anal dysplasia. Treatment guidelines for AIN are not yet available. Therapeutic strategies can be divided into topical (e.g. trichloroacetic acid, podophyllotoxin, imiquimod, photodynamic therapy) and ablative (e. g. surgical excision, laser ablation, infrared coagulation, electrocautery) measures. However, controlled studies on AIN treatment have not been performed. The impact of HPV vaccination on AIN development will also need to be assessed. Long‐term follow‐up of these patients is essential to gain more insight into the natural history of anogenital HPV infection in HIV‐positive MSM.     

Factors associated with clinical and sub-clinical anal human papillomavirus infection in homosexual men.

OBJECTIVES--(I) to determine the relative sensitivities of clinical examination, cytology and HPV DNA hybridisation for the detection of anal human papillomavirus infection; and (ii) to examine various factors which may influence presentation of anal human papillomavirus infection in homosexual men. METHODS AND RESULTS--112 unselected homosexual men attending a Sydney STD clinic for routine screening underwent a complete anogenital and physical examination, during which blood samples (for haematological, serological and immunological investigations), rectal swabs (for culture of anal pathogens) and anal scrapes of the dentate line (for cytology and HPV DNA hybridisation) were collected. Papanicolaou-stained anal smears were examined for cytological abnormalities, including those indicative of HPV infection or anal intraepithelial neoplasia (AIN). HPV DNA was detected by high stringency dot hybridisations using radiolabelled HPV 6, 11, 16 and 18 DNA probes. Visible anal condylomata, situated either externally or in the anal canal, were present in 26% of these men; 46% had cytological evidence of HPV infection, and 19% of the smears showed evidence of mild to moderate dysplastic changes (AIN I-II). Detectable HPV DNA was present in 40% of the anal scrapes. By combining these results, a total of 73 men (65%) were found to have at least one of the indicators of HPV infection. These data, together with that relating to HIV antibody, immune status and past or present infection with other STDs, was correlated with information obtained from a questionnaire administered to the patients at the time of their clinical examination. CONCLUSIONS--In this study cytology was found to be slightly more sensitive than HPV DNA dot hybridisation for the detection of HPV infection in the anal canal, providing the full range of HPV-associated cytological changes were accepted as a basis for diagnosis. Clinical anal lesions were more likely to be detected in young men, men who had symptomatic HIV infection and those with a history of past anal wart infection. The latter group also had a higher incidence of cytologically apparent HPV infection in their anal smears. There was a significant association between the detection of HPV 16/18 and the presence of anal dysplasia, but there were no significant correlations between HPV infection or anal dysplasia and HIV antibody, immune function status, sexual practices or history of other STDs.     

Lichen sclerosus is frequently present in penile squamous cell carcinomas but is not always associated with oncogenic human papillomavirus

BACKGROUND: Penile squamous cell carcinoma (SCC) may occur on pre-existing lesions of lichen sclerosus (LS). However, the prevalence of histological changes of LS in penile SCC is not well established. Moreover, mucosal oncogenic human papillomaviruses (HPVs) are sometimes detected in penile SCC, but have not been systematically sought in LS-associated penile SCC. OBJECTIVES: To establish the prevalence of LS histological changes and of mucosal oncogenic HPV in a series of patients with penile SCC. METHODS: Consecutive cases of histologically proven penile SCC from a single university hospital over a 14-year period were retrospectively selected and reviewed. Histological signs of LS were systematically sought. HPV was detected by polymerase chain reaction (PCR) amplification of DNA from paraffin-embedded skin samples using general primers GP5+/GP6+ (allowing detection of mucosal HPV) and oncogenic type 16-, 18-, 31- and 33-specific primers. RESULTS: Eighteen cases of penile SCC were found. The mean +/- SD age of patients at diagnosis was 67.3 (14.5 years). In eight of 18 (44%) cases, SCC was associated with histological features of LS. Seventeen skin biopsy specimens of SCC (nine without and eight with LS histology) were subjected to PCR amplification for HPV. Mucosal HPV was detected in six of them (35%). Five of nine SCCs without histological features of LS were positive for mucosal HPV: three with HPV type 16 and two with only general primers. In contrast, all eight SCCs associated with LS were negative for oncogenic HPV types, although one was positive with general primers. CONCLUSIONS: Penile SCC seems to be frequently associated with LS histological changes. As with vulval SCC, we found that non-LS-associated penile SCC tended to be frequently associated with oncogenic HPV infection, whereas LS-associated penile SCC was not. Larger series are needed to confirm this association.     

Human papillomavirus-associated squamous cell carcinoma of the nail bed in African-American patients

Background  Human papillomavirus (HPV) has been implicated in the development of digital squamous cell carcinoma (SCC). Case reports in the literature mostly identify HPV type 16 present in tumors, but HPV types 2, 31, 34, 35, and 73 have also been isolated.
Methods  Two cases of digital SCC associated with HPV 16 in young African-American men are presented.
Results and conclusions  Digital SCC associated with HPV may be difficult to evaluate and treat, particularly in African-Americans and patients with human immunodeficiency virus (HIV). We discuss the need for careful evaluation, treatment, and follow-up of these individuals.     

Skin as an indicator for sexually transmitted infections

Cutaneous signs and skin conditions associated with sexually transmitted infections (STIs) are discussed. Syphilis, condyloma acuminata, and scabies are well-known STIs with cutaneous manifestations. Chlamydia and gonorrhea can also cause specific muco-cutaneous signs and symptoms. HIV often manifests itself through skin conditions. Dermatologists are pivotal in the timely diagnosis of HIV infection and play an important role in the disease prognosis and ongoing transmission. Anal intra-epithelial neoplasia (AIN), an HPV related precursor of anal carcinoma affecting HIV positive men, is a relatively new condition that many dermatologists will face in the future. STIs should be involved in the differential diagnosis when dermatologists are confronted with anogenital dermatoses, especially in patients with an increased risk for STIs.     

Human papillomavirus type 16 in a homosexual man. Association with perianal carcinoma in situ and condyloma acuminatum.

BACKGROUND--The association of anal carcinoma with human papillomavirus (HPV) type 16 infection is well documented. Anal carcinoma is also frequently associated with a history of anogenital condylomata. More than 90% of anogenital condylomata contain HPV type 6 or 11. It is rare for a condylomatous lesion to contain HPV 16. We report the unusual case of a homosexual man, testing positively for human immunodeficiency virus, with carcinoma in situ evolving within perianal condylomata infected with HPV 16. OBSERVATIONS--Microscopic examination of tissue specimens from ulcerated verrucous lesions on the perianal mucosa revealed changes of classic condylomata acuminata with contiguous focal squamous cell carcinoma in situ. Testing for HPV DNA by in situ hybridization identified HPV 16 in both the condylomatous and carcinoma in situ areas. CONCLUSIONS--The association of HPV 16-infected condylomata and adjacent carcinoma in situ implies that cutaneous genital condylomata may progress to high-grade lesions. Given that homosexual men are at high risk for perianal carcinomas, HPV typing of perianal condylomata specimens may help identify immunocompromised patients who are at risk for the development of carcinomas.     

尖锐湿疣凹空细胞的观察

本文对９７例尖锐湿疣（ＣＡ）进行聚合酶链反应检测人乳头瘤病毒（ＨＰＶ）ＤＮＡ及光镜下观察凹空细胞的特征。结果显示，９５例有凹空细胞，占９７．９４％。凹空细胞多分布在棘层的中、上层。根据核的改变将凹空细胞分为九型，以镰刀形核、毛虫样核和核大浓染型出现例数最多，分别为７５／９５、７４／９５和６１／９５，此三型对ＣＡ最有诊断价值。ＨＰＶ６、１１阳性９３例（９５．８８％），ＨＰＶ１６、１８、３１、３３、５２ｂ、５８阳性２例（２．０６％），ＨＰＶ６、１１、１６、１８、３１、３３、５２ｂ、５８阴性２例（２．０６％），但有典型的凹空细胞。２例ＣＡ无凹空细胞而ＨＰＶ６、１１为阳性。     

Detection of mucosal human papilloma virus DNA in bowenoid papulosis, Bowen's disease and squamous cell carcinoma of the skin

Human papilloma virus (HPV) is known to be an etiologic agent for benign warts of the skin. Recently, HPV have been detected in malignant skin and mucosal diseases suggesting that HPV infection can induce malignant skin tumors. In the present study, we examined the presence of mucosal HPV DNA in normal tissue, Bowen's disease (BD), Bowenoid papulosis (BP) and squamous cell carcinoma (SCC) of the skin. We detected the HPV DNA with polymerase chain reactions, and identified the type by DNA sequencing. In the results, we detected HPV DNA in none of the 17 normal controls, two of the three BP (66.7%), one of the 21 BD (4.8%), and six of the 26 SCC of the skin samples (23.0%). The occurrence rates of HPV in BP and SCC were significantly elevated compared to that of normal controls (P < 0.01 and P < 0.01, respectively). In addition, the occurrence rate of HPV in BP was significantly elevated compared to that of BD (P < 0.05). The reproducibility was confirmed with a polymerase chain reaction (PCR) with another primer pair. Of the two cases of BP with positive HPV DNA, one case showed HPV 31 and the other case HPV 16. The case of BD with positive HPV DNA showed HPV 31. Of the six cases of SCC with positive HPV DNA, one case showed HPV 16, another case HPV 34, and the other four cases HPV 31. These results showed that mucosal HPV, including HPV 31 and 16, could be detected in SSC of the skin. Mucosal HPV, not only the epidermodysplasia verruciformis type, appear to induce malignant skin tumors.     

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 intercourse: a risk factor for anal papillomavirus infection in women?

OBJECTIVE--To determine whether anal intercourse is a risk factor for anal HPV infection in women. DESIGN--Results derived from clinical examination, anal cytology and HPV DNA hybridisation were correlated with data obtained from a questionnaire administered to the patients at the time of their clinical examination. SETTING--A sexually transmitted diseases (STD) clinic in Sydney, Australia. SUBJECTS--31 women attending the clinic for HPV related problems. METHODS AND RESULTS--A thorough history was elicited from each woman followed by physical examination of the anogenital region. Cervical and anal scrapes were collected for cytology and HPV DNA hybridisation. Of the 15 women who practised anal intercourse, a total of 12 (80%) had either clinical or subclinical HPV infection. Seven had overt anal warts, situated either internally or externally in the anal canal; and further 5 women had evidence of subclinical HPV infection as determined by positive cytological and/or HPV DNA hybridisation results on their anal scrapes. The women who did not have a history of anal intercourse had a lower (7/16, 43%), but not statistically significant, rate of anal HPV infection: five had anal warts and two had subclinical evidence of infection. No correlations were found between anal HPV infection and genital (cervical, vulval or vaginal) HPV infection; nor between the HPV typing patterns of women in either group. CONCLUSION--The results obtained from these women do not indicate a close relationship between anal intercourse and the presence of detectable anal HPV infection.     

Human papillomavirus types 16 and 39 in a vulval carcinoma occurring in a woman with Hailey-Hailey disease

A woman with Hailey-Hailey disease, suffering from carcinoma of the vulva, was examined by histology and for the presence of human papillomavirus (HPV) DNA by polymerase chain reaction (PCR) and in situ hybridization. Our diagnosis by histological examination revealed the vulval carcinoma to be a squamous cell carcinoma (SCC), adjacent to lesions of Hailey-Hailey disease and severe dysplasia/carcinoma in situ [vulval intraepithelial neoplasia (VIN) III]. The PCR with consensus primers for the L1 region (L1-PCR) successfully amplified HPV DNA using total DNA extracted from formalin-fixed and paraffin-embedded tissue specimens. Restriction fragment length polymorphism analysis and sequencing of L1-PCR products revealed HPV types 16 and 39. HPV 16-specific primers for the E6 region identified HPV 16 DNA. In situ hybridization analysis with biotinylated HPV 16 and 39 DNA probes revealed the presence of the HPV 39 genome in the nuclei of the tumour cells in the SCC. These results indicate that HPV 16 and 39 are associated with lesions in vulval carcinoma. Regarding the patient's susceptibility to infection in the case of Hailey-Hailey disease, there is a possibility that HPV was inoculated into the lesions of Hailey-Hailey disease and induced those of VIN III and SCC.     

Human papillomavirus infection in men who have sex with men participating in a Dutch gay-cohort study

BACKGROUND: To develop strategies for prevention and early treatment of human papillomavirus (HPV) anal and penile cancer, a better understanding of related sexual behavior risk factors is needed. GOAL: The goal of this study was to establish the prevalence of anal and coronal sulcus HPV in a group of men who have sex with men participating in a Dutch gay-cohort study, to identify risk factors associated with HPV infection in this group, and to investigate the presence of identical HPV types in couples with stable relationships. STUDY DESIGN: A cross-sectional study of 241 HIV-negative and 17 HIV-positive men who have sex with men visiting the sexually transmitted disease clinic of the Erasmus MC for a regular and scheduled examination. Participants underwent a routine venereological examination including HIV serologic analysis, and swabs were taken from the coronal sulcus and anus for HPV DNA testing. All subjects were asked to complete a questionnaire on sexual risk behavior. RESULTS: HPV DNA was detected at the coronal sulcus in 23.5% of the HIV-positive men and in 15.8% of the HIV-negative men (P=0.492). In anal specimens, HPV DNA was detected in 64.7% of the HIV-positive men and 32.8% of the HIV-negative men (P=0.015). High-risk HPV types (P=0.007) and 2 or more different HPV genotypes (P=0.006) were seen more often in anal specimens of HIV-positive persons than in specimens of HIV-negative persons. A factor possibly associated with the presence of anal HPV infection was a concomitant anal infection with Chlamydia trachomatis, gonococci, or herpes simplex virus (P=0.059). In only 16.7% of HPV-positive steady couples, both companions showed the presence of one or more identical HPV genotypes. CONCLUSION: In this study, anal HPV DNA was detected more often than HPV DNA at the coronal sulcus. HIV positivity was associated with a higher prevalence of high-risk, but not with low-risk HPV types, at the anus. No association was found between HIV positivity and presence of high-risk HPV at the coronal sulcus. No sexual behavioral determinants for the presence of HPV could be identified. Concomitant anal infection with C trachomatis, gonococci, or herpes simplex virus may be associated with HPV infection. In the majority of steady couples, partners were infected with different HPV types.