RESUMEN

OBJECTIVES: To provide an outline of the existing data on penile intraepithelial neoplasia (PeIN), as well as a narrative review on imiquimod (IQ; a toll-like receptor 7 agonist) treatment and immune microenvironment markers that may predict response to treatment. METHODS: A narrative review of the literature from 2000 to the present was conducted on PubMed, and we describe the most relevant data and cross references. RESULTS: The incidence of PeIN is increasing. Local therapy with IQ may offer an easy applicable treatment with complete response rates of up to 63% but can be associated with considerable side-effects. There is no conclusive data on the optimal treatment schedule for PeIN, but evaluation of treatment results for other human papillomavirus-related pre-malignancies suggest three times a week for a duration up to 16 weeks. There are no published studies concerning the PeIN immune microenvironment. However, findings from the few studies on penile cancer and pre-cancerous vulvar and cervical lesions imply that specific immune cell subpopulations can serve as future predictors for successful immunomodulation treatments such as IQ. CONCLUSIONS: Overall, limited data are available on IQ treatment for PeIN and no published data exists on the PeIN immune microenvironment. Further translational studies are warranted to gain more understanding on the pathophysiology of PeIN and potential predictors of progression and of response to topical treatments.

RESUMEN

Neoplasm of the penis is relatively rare in most regions representing 0-2% of cancers worldwide. While the penis can be affected by sarcomas, basal cell carcinomas or even melanoma, Penile Squamous Cell Carcinoma (PSCC) represents approximately 95% of all penile neoplasms. Despite its rarity and most common presentation at later decades of life most individuals diagnosed with PSCC are faced with significant decrease in quality of life. The prevalence and incidence vary among different regions and populations, but a common trend is for diagnosis to occur late (stage 4). Underdeveloped countries are traditionally reported to have higher incidence rates; however, rates may vary significantly between urban and rural areas even in developed countries. Age adjusted rates are on the rise in some countries that used to have incidence rates of 1:100 000 or less. The list of associated risk factors is long and includes among others, lack of neonatal circumcision, poor genital hygiene, socioeconomic status, history of human papillomavirus (HPV) infection and penile intraepithelial neoplasia (PeIN). Many risk factors are widely debated among experts however HPV and PeIN are indisputable risk factors, and both also form part of the classification system for PSCC. Both conditions may have occurred in the past or be present at the time of diagnosis and identifying them plays a major role in management strategies. For such a rare condition PSCC can present in many different forms clinically making diagnosis no easy feat. Diagnosis of PSCC is done through clinical examination, including lymph node palpation, followed by a biopsy, which is essential for the classification. Lymph node involvement is a common finding at first presentation and investigation of spread to deep nodes is important and can be done with the aid of PET-CT. Treatment options for PSCC include surgery, chemotherapy, and radiation therapy. Surgical removal of the tumor is considered the most effective however can lead to severe decrease of quality of life. Chemotherapy is used in the case of fixed or bulky lymph nodes, where surgery is not indicated, and for distant metastasis. Radiation therapy is particularly effective in the case of HPV-positive PSCC.

RESUMEN

OBJECTIVES: Human papillomavirus (HPV) is the most common sexually transmitted infection globally, which causes nearly all cervix carcinomas and contributes to oropharyngeal, penile, vulva, vagina, and anal cancers. Despite the role of HPV in several preneoplastic and cancerous lesions in men, male vaccine coverage is low. This article aims to provide insights into the pathophysiology of HPV-related penile cancer and penile intraepithelial neoplasia (PeIN). Moreover, this review endeavors to outline the advantages of implementing HPV vaccination in male vaccination programs and the role of health care providers in this mission. DATA SOURCES: This is a narrative review of relevant literature. A search on PubMed and Cochrane database was conducted. The following search terms were used: HPV vaccination, gender-neutral vaccination, male, genital warts, penile cancer, vaccine recommendations. CONCLUSION: HPV is responsible for 50.8% of penile cancers globally, 79.8% of PeIN, and 90% of genital warts. In 2009 the Food and Drug Administration licensed the quadrivalent HPV vaccine for use in males, with a potential efficacy of 90% and 77.5% to reduce genital warts and anal intraepithelial neoplasia, respectively. However, the uptake of HPV vaccination in men is low, and gender-neutral vaccination is estimated to be implemented only in 42 countries worldwide. Because data in penile cancer are lacking, further research is needed to study the efficacy of incorporation of HPV vaccines in male vaccination programs on preventing penile cancer and PeIN. IMPLICATIONS FOR NURSING PRACTICE: Nurses and other members of the multidisciplinary team should take every opportunity to recommend HPV vaccination in adolescent men. Moreover, they play an important role in raising community awareness about the incidence of HPV and the related range of diseases. A practical approach is needed to incorporate HPV vaccines in vaccination programs and to optimize vaccination coverage.

Asunto(s)

Condiloma Acuminado , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Pene , Adolescente , Femenino , Humanos , Masculino , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/uso terapéutico , Neoplasias del Pene/epidemiología , Neoplasias del Pene/prevención & control , Vacunación

RESUMEN

Penile intraepithelial neoplasia (PeIN) is a rare skin condition with potential to progress to invasive penile cancer. We performed a systematic review of treatment options and outcomes for PeIN. Topical agents showed response and recurrence rates of 40-100% and 20% for imiquimod, and 48-74% and 11% for 5-fluorouracil, respectively. Discontinuation of topical agents because of side effects was observed in 12% of cases. Response rates for laser therapies were 52-100%, with recurrence in 7-48% of cases and a change in penile sensitivity in 50%. Circumcision cleared preputial PeIN. Rates of recurrence after surgical treatment of glans PeIN were 25% for wide local excision, 4% for Mohs surgery, 5% for total glans resurfacing, and 10% for glansectomy. There are limited data on factors predictive of treatment response and on sequencing of treatment options. PATIENT SUMMARY: Several treatment options are available for men with precancerous lesions of the foreskin or glans. Close follow-up is necessary as lesions can recur or progress to invasive penile cancer.

Asunto(s)

Carcinoma in Situ , Carcinoma de Células Escamosas , Neoplasias del Pene , Lesiones Precancerosas , Carcinoma in Situ/patología , Carcinoma in Situ/cirugía , Carcinoma de Células Escamosas/patología , Humanos , Masculino , Neoplasias del Pene/patología , Neoplasias del Pene/cirugía , Pene/patología , Pene/cirugía , Lesiones Precancerosas/patología , Lesiones Precancerosas/cirugía

RESUMEN

PURPOSE: Squamous cell carcinoma (SCC) of the penis is rare. Some studies have suggested that the incidence is increasing but the available literature is equivocal. We examined the incidence of high-grade penile intraepithelial neoplasia (PeIN), the incidence and 5-year relative survival as well as mortality of penile SCC in Denmark over the latest 20 years. METHODS: New cases of high-grade PeIN and penile cancer were identified from high-quality nationwide registries. Age-standardized (World) incidence rates per 100,000 person-years and average annual percentage change (AAPC) were estimated. For penile SCC, 5-year relative survival was calculated, and Cox regression was used to examine the effect of selected characteristics on mortality. RESULTS: Altogether, 1,070 new cases of high-grade PeIN were diagnosed (1997-2018) and the incidence increased from 0.87 to 1.84 per 100,000 person-years from 1997-1998 to 2017-2018 (AAPC = 4.73; 95% CI: 3.54-5.94). We identified 1,216 penile cancer cases (1997-2018) (95.7% SCC). The incidence of penile SCC increased slightly from 0.85 per 100,000 person-years in 1997-1998 to 1.13 per 100,000 person-years in 2017-2018 (AAPC = 1.01; 95% CI: 0.24-1.79). The 5-year relative survival of penile SCC did not change substantially, whereas the mortality tended to decrease. CONCLUSION: Penile SCC is increasing slightly in Denmark, while a pronounced increase in the incidence of high-grade PeIN is seen. The 5-year relative survival from penile cancer was relatively stable over time. Increasing exposure to HPV infection at the population level may have contributed to the observed increase in PeIN and penile SCC. Awareness of HPV may also have contributed to the increased detection of PeIN.

Asunto(s)

Carcinoma in Situ , Infecciones por Papillomavirus , Neoplasias del Pene , Carcinoma in Situ/epidemiología , Dinamarca/epidemiología , Humanos , Incidencia , Masculino , Neoplasias del Pene/epidemiología , Pene

RESUMEN

Penile cancer is an under-studied disease that occurs more commonly in developing countries and 30-50% of cases show high-risk human papillomavirus (HPV) infection. Therapeutic advances are slow, largely due to the absence of animal models for translational research. Here, we report the first mouse model for HPV-related penile cancer. Ten-week-old mice expressing all the HPV16 early genes under control of the cytokeratin 14 (Krt14) gene promoter and matched wild-type controls were exposed topically to dimethylbenz(a)anthracene (DMBA) or vehicle for 16 weeks. At 30 weeks of age, mice were sacrificed for histological analysis. Expression of Ki67, cytokeratin 14, and of the HPV16 oncogenes E6 and E7 was confirmed using immunohistochemistry and quantitative PCR, respectively. HPV16-transgenic mice developed intraepithelial lesions including condylomas and penile intraepithelial neoplasia (PeIN). Lesions expressed cytokeratin 14 and the HPV16 oncogenes E6 and E7 and showed deregulated cell proliferation, demonstrated by Ki67-positive supra-basal cells. HPV16-transgenic mice exposed to DMBA showed increased PeIN incidence and squamous cell carcinoma. Malignant lesions showed varied histological features closely resembling those of HPV-associated human penile cancers. Wild-type mice showed no malignant or pre-malignant lesions even when exposed to DMBA. These observations provide the first experimental evidence to support the etiological role of HPV16 in penile carcinogenesis. Importantly, this is the first mouse model to recapitulate key steps of HPV-related penile carcinogenesis and to reproduce morphological and molecular features of human penile cancer, providing a unique in vivo tool for studying its biology and advancing basic and translational research. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Asunto(s)

Carcinoma in Situ/virología , Carcinoma de Células Escamosas/virología , Papillomavirus Humano 16/fisiología , Infecciones por Papillomavirus/virología , Neoplasias del Pene/virología , Animales , Carcinogénesis , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/patología , Proliferación Celular , Modelos Animales de Enfermedad , Papillomavirus Humano 16/genética , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Transgénicos , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecciones por Papillomavirus/patología , Neoplasias del Pene/patología , Pene/patología , Pene/virología , Distribución Aleatoria , Proteínas Represoras/genética , Proteínas Represoras/metabolismo

RESUMEN

Penile cancer is a rare condition and can be very complex to manage. Advances in surgical techniques, imaging, pathological classification and patient pathways have led to improved patient care. The diagnosis of pre-malignant change, penile cancer and metastatic disease along with advances in their treatment are detailed in this review which aims to update clinicians from multiple specialties and countries on penile cancer.

Asunto(s)

Neoplasias del Pene/diagnóstico , Neoplasias del Pene/terapia , Humanos , Masculino , Metástasis de la Neoplasia , Lesiones Precancerosas/diagnóstico

RESUMEN

Studies on risk factors for penile intraepithelial neo-plasia have been small in size, have not distinguished penile intraepithelial neoplasia from invasive cancer, and have relied on self-reported information. This study investigated risk factors for penile intraepithelial neoplasia in a cohort of 580 penile intraepithelial neoplasia cases and 3,436 controls using information from 7 Swedish registers. Cases with penile intraepithelial neoplasia had increased odds ratios (ORs) for inflammatory skin diseases (14.7, 95% CI 6.5-33.4) including lichen planus (12.0, 95% CI 3.0-48.0), indicating lichen planus to be an important risk factor. Increased ORs were also observed for diseases of the prepuce (4.0, 95% CI 2.2-7.4), immunosuppressive drugs (5.0, 95% CI 2.5-9.8), penile surgical procedures (4.8, 95% CI 2.2-10.8), balanitis (9.2, 95% CI 5.0-16.8), genital warts (9.9, 95% CI 4.3-22.7) and organ transplantation (7.0, 95% CI 2.4-20.8). This study demonstrates important risk factors for penile intraepithelial neoplasia, providing knowledge that can help prevent the development of penile cancer.

Asunto(s)

Carcinoma in Situ/epidemiología , Neoplasias del Pene/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma in Situ/patología , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana Edad , Neoplasias del Pene/patología , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Suecia/epidemiología , Adulto Joven

RESUMEN

Penile cancer is a rare malignancy estimated to affect 26,000 men globally each year. The association with penile cancer, in particular non-invasive disease, and human papilloma virus (HPV) is well known. Ninety-five percent of cases of penile cancer are squamous cell carcinoma (SCC), which are staged using the TNM staging system. Terminology describing the histological appearance of non-invasive penile cancer has changed with all cases grouped under the umbrella term of penile intraepithelial neoplasia (PeIN); either undifferentiated or differentiated. This replaces previous terms such as carcinoma in situ (CIS) and eponymous names such as Bowen's disease. This change is recognised by the World Health Organisation (WHO). The topical treatments most commonly used for PeIN are 5-fluorouracil (5-FU) and imiquimod (IQ). Other treatments such as photodynamic therapy (PDT) are used but to a lesser degree. The evidence for all of these treatments is heterogenous with no randomised data available. Overall up to 57% complete response has been reported with a low number of serious adverse events. In this article, we aim to review the available evidence for the topical treatment of non-invasive penile cancer specifically regarding its efficacy and toxicity.

RESUMEN

Abstract The aims of this study were to determine the incidence of external genital lesions (EGLs), specifically histologically confirmed condyloma (genital warts) and Penile Intraepithelial Neoplasia (PeIN), and genital HPV infection progression to EGLs among healthy men aged 18-73 residing in Brazil. Subjects included 1118 men enrolled in the HPV Infection in Men (HIM) study between July 2005 and June 2009. At each visit, EGLs were biopsied and subjected to pathological evaluation. HPV status in genital swabs and biopsies was determined by Linear Array and INNO-LiPA, respectively. Age-specific EGLs incidence and the proportion and median time to EGL development were estimated. Kaplan-Meier cumulative incidence rates at 6, 12, and 24 months were determined. During follow-up, 73 men developed an incident EGL. Men could develop multiple EGLs and there were 36 men with condyloma, 27 men with lesions suggestive of condyloma, six men with PeIN, and 20 men with non-HPV lesions. HPV-positive men who developed EGLs were younger (p = 0.002) than men that did not develop lesions. Among the 815 men with HPV infection, 4% progressed to EGL with the same HPV detected in the swab. During follow up, 15.7% of genital HPV-6 and HPV-11 infections progressed to condyloma (median progression time of nine months for HPV-6 versus 6.8 months for HPV-11). Approximately 1% of HPV-16 infections progressed to PeIN with a median progression time of 25 months. HPV types covered by the 4-valent HPV vaccine were detected in 82.3% and 83.3% of condyloma and PeIN, respectively. The high burden of HPV and high frequency of progression to disease underscores the need to offer HPV prophylactic vaccination to men to reduce the overall burden of infection and diseases caused by HPV.

Asunto(s)

Humanos , Masculino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Papillomaviridae/genética , Enfermedades del Pene/epidemiología , Condiloma Acuminado/epidemiología , Papillomaviridae/clasificación , Enfermedades del Pene/diagnóstico , Enfermedades del Pene/virología , Brasil/epidemiología , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/virología , Incidencia , Progresión de la Enfermedad , Genotipo

RESUMEN

The aims of this study were to determine the incidence of external genital lesions (EGLs), specifically histologically confirmed condyloma (genital warts) and Penile Intraepithelial Neoplasia (PeIN), and genital HPV infection progression to EGLs among healthy men aged 18-73 residing in Brazil. Subjects included 1118 men enrolled in the HPV Infection in Men (HIM) study between July 2005 and June 2009. At each visit, EGLs were biopsied and subjected to pathological evaluation. HPV status in genital swabs and biopsies was determined by Linear Array and INNO-LiPA, respectively. Age-specific EGLs incidence and the proportion and median time to EGL development were estimated. Kaplan-Meier cumulative incidence rates at 6, 12, and 24 months were determined. During follow-up, 73 men developed an incident EGL. Men could develop multiple EGLs and there were 36 men with condyloma, 27 men with lesions suggestive of condyloma, six men with PeIN, and 20 men with non-HPV lesions. HPV-positive men who developed EGLs were younger (p=0.002) than men that did not develop lesions. Among the 815 men with HPV infection, 4% progressed to EGL with the same HPV detected in the swab. During follow up, 15.7% of genital HPV-6 and HPV-11 infections progressed to condyloma (median progression time of nine months for HPV-6 versus 6.8 months for HPV-11). Approximately 1% of HPV-16 infections progressed to PeIN with a median progression time of 25 months. HPV types covered by the 4-valent HPV vaccine were detected in 82.3% and 83.3% of condyloma and PeIN, respectively. The high burden of HPV and high frequency of progression to disease underscores the need to offer HPV prophylactic vaccination to men to reduce the overall burden of infection and diseases caused by HPV.

Asunto(s)

Condiloma Acuminado/epidemiología , Papillomaviridae/genética , Enfermedades del Pene/epidemiología , Adolescente , Adulto , Anciano , Brasil/epidemiología , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/virología , Progresión de la Enfermedad , Genotipo , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Papillomaviridae/clasificación , Enfermedades del Pene/diagnóstico , Enfermedades del Pene/virología , Adulto Joven

RESUMEN

The purpose of this study was to assess whether the incidence of histopathologically confirmed condyloma and penile intraepithelial neoplasia (PeIN) and rates of genital HPV infection progression to these lesions differs by country (Brazil, Mexico and the U.S.). At each visit, lesions were biopsied and were categorized by pathologic diagnoses. The Linear Array genotyping method was used to identify HPV genotypes from genital swabs, while the INNO-LiPA HPV Genotyping Extra method was used for tissue specimens. Age-specific analyses were conducted for lesion incidence by country, with Kaplan-Meier estimation of cumulative incidence. The proportion of HPV infections that progressed to condyloma and PeIN, the median time to lesion development and the incidence rates were estimated by country. When comparing demographic and sexual characteristics across the three countries, sexual orientation (p = 0.008) and lifetime number of female sexual partners (p < 0.0001) were differentially associated with lesion incidence in the three countries. Condyloma incidence in Brazil and the U.S. decreased with age, while incidence remained constant across the lifespan in Mexico. There were no differences by country and age for PeIN incidence. HPV types 6 and 11 were the most common types to progress to condyloma and HPV types 16, 6 and 11 were the most common types to progress to PeIN in all three countries. The continuous risk of condyloma and PeIN across all age groups and countries in this study emphasizes the need to ensure that strong HPV immunity, such as that obtained through vaccination, is maintained across the lifespan of men.

Asunto(s)

Enfermedades de los Genitales Masculinos/epidemiología , Enfermedades de los Genitales Masculinos/virología , Infecciones por Papillomavirus/epidemiología , Adolescente , Adulto , Anciano , Brasil/epidemiología , Enfermedades de los Genitales Masculinos/etiología , Genotipo , Humanos , Incidencia , Masculino , México/epidemiología , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/etiología , Infecciones por Papillomavirus/virología , Factores de Riesgo , Conducta Sexual/psicología , Parejas Sexuales/psicología , Estados Unidos/epidemiología , Adulto Joven

RESUMEN

Penile cancer is a rare and devastating disease, especially at advanced stages. The etiology of penile cancer is multifactorial with multiple established risk factors including infection with the human papillomavirus (HPV). Approximately 40% of penile cancers are attributable to HPV, although the literature describing HPV as a prognostic factor is mixed. The pathogenesis of HPV infection as well as vaccination practices may provide valuable therapeutic agents to treat this rare and difficult disease.

Asunto(s)

Carcinogénesis , Papillomaviridae/inmunología , Infecciones por Papillomavirus/complicaciones , Vacunas contra Papillomavirus/uso terapéutico , Neoplasias del Pene/etiología , Pene/virología , Vacunación/métodos , Humanos , Masculino , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Neoplasias del Pene/prevención & control , Neoplasias del Pene/virología , Factores de Riesgo

RESUMEN

BACKGROUND: Human papillomavirus (HPV) causes two types of external genital lesions (EGLs) in men: genital warts (condyloma) and penile intraepithelial neoplasia (PeIN). OBJECTIVE: The purpose of this study was to describe genital HPV progression to a histopathologically confirmed HPV-related EGL. DESIGN, SETTING, AND PARTICIPANTS: A prospective analysis nested within the HPV Infection in Men (HIM) study was conducted among 3033 men. At each visit, visually distinct EGLs were biopsied; the biopsy specimens were subjected to pathologic evaluation and categorized by pathologic diagnoses. Genital swabs and biopsies were used to identify HPV types using the Linear Array genotyping method for swabs and INNO-LiPA for biopsy specimens. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: EGL incidence was determined among 1788 HPV-positive men, and cumulative incidence rates at 6, 12, and 24 mo were estimated. The proportion of HPV infections that progressed to EGL was also calculated, along with median time to EGL development. RESULTS AND LIMITATIONS: Among 1788 HPV-positive men, 92 developed an incident EGL during follow-up (9 PeIN and 86 condyloma). During the first 12 mo of follow-up, 16% of men with a genital HPV 6 infection developed an HPV 6-positive condyloma, and 22% of genital HPV 11 infections progressed to an HPV 11-positive condyloma. During the first 12 mo of follow-up, 0.5% of men with a genital HPV 16 infection developed an HPV 16-positive PeIN. Although we expected PeIN to be a rare event, the sample size for PeIN (n=10) limited the types of analyses that could be performed. CONCLUSIONS: Most EGLs develop following infection with HPV 6, 11, or 16, all of which could be prevented with the 4-valent HPV vaccine. PATIENT SUMMARY: In this study, we looked at genital human papillomavirus (HPV) infections that can cause lesions in men. The HPV that we detected within the lesions could be prevented by a vaccine.

Asunto(s)

Carcinoma in Situ/epidemiología , Condiloma Acuminado/epidemiología , Papillomavirus Humano 11/aislamiento & purificación , Papillomavirus Humano 16/aislamiento & purificación , Neoplasias del Pene/epidemiología , Adolescente , Adulto , Anciano , Brasil/epidemiología , Carcinoma in Situ/patología , Carcinoma in Situ/virología , Condiloma Acuminado/patología , Condiloma Acuminado/virología , Progresión de la Enfermedad , Estudios de Seguimiento , Genotipo , Papillomavirus Humano 11/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 6/genética , Papillomavirus Humano 6/aislamiento & purificación , Humanos , Incidencia , Masculino , México/epidemiología , Persona de Mediana Edad , Neoplasias del Pene/patología , Neoplasias del Pene/virología , Prevalencia , Estudios Prospectivos , Estados Unidos/epidemiología , Adulto Joven

RESUMEN

Early HPV infection in males is difficult to detect clinically and pathologically. This study assessed histopathology in diagnosing male genital HPV. External genital lesions (n = 352) were biopsied, diagnosed by a dermatopathologist, and HPV genotyped. A subset (n = 167) was diagnosed independently by a second dermatopathologist and also re-evaluated in detail, tabulating the presence of a set of histopathologic characteristics related to HPV infection. Cases that received discrepant diagnoses or HPV-related diagnoses were evaluated by a third dermatopathologist (n = 163). Across dermatopathologists, three-way concordance was fair (k = 0.30). Pairwise concordance for condyloma was fair to good (k = 0.30-0.67) and poor to moderate for penile intraepithelial neoplasia (k = -0.05 to 0.42). Diagnoses were 44-47% sensitive and 65-72% specific for HPV 6/11-containing lesions, and 20-37% sensitive and 98-99% specific for HPV 16/18. Presence of HPV 6/11 was 75-79% sensitive and 35% specific for predicting pathologic diagnosis of condyloma. For diagnosis of penile intraepithelial neoplasia, HPV 16/18 was 95-96% specific but only 40-64% sensitive. Rounded papillomatosis, hypergranulosis, and dilated vessels were significantly (P < 0.05) associated with HPV 6/11. Dysplasia was significantly (P = 0.001) associated with HPV 16/18. Dermatopathologists' diagnoses of early male genital HPV-related lesions appear discordant with low sensitivity, while genotyping may overestimate clinically significant HPV-related disease. Rounded papillomatosis, hypergranulosis, and dilated vessels may help establish diagnosis of early condyloma.

Asunto(s)

Enfermedades de los Genitales Masculinos/diagnóstico , Enfermedades de los Genitales Masculinos/patología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Neoplasias del Pene/diagnóstico , Neoplasias del Pene/virología , Adulto , Biopsia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patología , Carcinoma in Situ/virología , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/patología , Condiloma Acuminado/virología , Genotipo , Papillomavirus Humano 11/genética , Papillomavirus Humano 11/aislamiento & purificación , Papillomavirus Humano 11/patogenicidad , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 16/patogenicidad , Humanos , Masculino , Papillomaviridae/genética , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/virología , Pene/patología , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad

RESUMEN

BACKGROUND: Human papillomavirus (HPV) causes external genital lesions (EGLs) in men, including condyloma and penile intraepithelial neoplasia (PeIN). We sought to determine the incidence of pathologically confirmed EGLs, by lesion type, among men in different age groups and to evaluate the HPV types that were associated with EGL development. METHODS: HPV Infection in Men (HIM) study participants who contributed ≥2 visits from 2009-2013 were included in the biopsy cohort. Genotyping by an HPV line-probe assay was performed on all pathologically confirmed EGLs. Age-specific analyses were conducted for incident EGLs, with Kaplan-Meier estimation of cumulative incidence. RESULTS: This biopsy cohort included 2754 men (median follow-up duration, 12.4 months [interquartile range, 6.9-19.2 months]). EGLs (n = 377) were pathologically confirmed in 228 men, 198 of whom had incident EGLs. The cumulative incidence of any EGL was highest among men <45 years old and, for condyloma, decreased significantly over time with age. The genotype-specific incidence of EGL varied by pathological diagnoses, with high- and low-risk genotypes found in 15.6% and 73.2% of EGLs, respectively. Condyloma primarily contained HPV 6 or 11. While PeIN lesions primarily contained HPV 16, 1 PeIN III lesion was positive for HPV 6 only. CONCLUSION: Low- and high-risk HPV genotypes contribute to the EGL burden. Men remain susceptible to HPV-related EGLs throughout the life span, making it necessary to ensure the longevity of immune protection against the most common causative HPV genotypes.

Asunto(s)

Condiloma Acuminado/virología , Neoplasias de los Genitales Masculinos/virología , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Pene/patología , Adolescente , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Condiloma Acuminado/epidemiología , Condiloma Acuminado/patología , Estudios de Seguimiento , Neoplasias de los Genitales Masculinos/epidemiología , Neoplasias de los Genitales Masculinos/patología , Genotipo , Papillomavirus Humano 11/genética , Papillomavirus Humano 11/aislamiento & purificación , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 6/genética , Papillomavirus Humano 6/aislamiento & purificación , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/patología , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Adulto Joven

RESUMEN

BACKGROUND: Cutaneous human papillomaviruses (HPVs) may be associated with cutaneous epithelial lesions and non-melanoma skin cancers. No study has systematically evaluated the presence of genus beta [ß]-HPV in male genital skin or external genital lesions (EGLs) OBJECTIVES: To examine cutaneous ß-HPV types detected on the surface of EGLs in men and describe their presence prior to EGL development. STUDY DESIGN: A retrospective case series was conducted among 69 men with pathologically confirmed EGLs (n=72) who participated in the HPV Infection in Men Study. Archived exfoliated cells collected from the surface of each EGL and normal genital skin specimens 6-12 months preceding EGL development were tested for ß-HPV DNA using a type-specific multiplex genotyping assay. RESULTS: ß-HPV DNA was detected on 61.1% of all EGLs, with types 38 (16.7%), 5 (15.3%), and 12 (12.5%) most commonly identified. HPV prevalence differed across pathological diagnoses, with the largest number of ß-HPV types detected on condylomas. Most ß-HPV types were detected on normal genital skin prior to EGL development, though the prevalence was lower on EGLs compared to preceding normal genital skin. CONCLUSIONS: EGLs and the normal genital skin of men harbor a large number of ß-HPV types; however, it appears that ß-HPVs are unrelated to EGL development in men. Despite evidence to support a causal role in skin carcinogenesis at UVR-exposed sites, cutaneous HPV appears unlikely to cause disease at the UVR-unexposed genitals.

Asunto(s)

Condiloma Acuminado/virología , Genitales Masculinos/virología , Papillomaviridae/aislamiento & purificación , Adolescente , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Papillomaviridae/clasificación , Papillomaviridae/genética , Estudios Retrospectivos , Adulto Joven

RESUMEN

PURPOSE: Lichen sclerosus is an inflammatory skin disorder affecting anogenital areas in males and females that is associated with squamous cell carcinoma. However, there is a lack of data on the role of biomarkers for predicting lichen sclerosus progression to squamous cell carcinoma. We focused on early protein markers of squamous cell carcinoma and their expression in lichen sclerosus to improve the mechanistic and diagnostic understanding of lichen sclerosus. MATERIAL AND METHODS: We performed an extensive PubMed® and MEDLINE® search for protein markers found in early stages of vulvar and penile squamous cell carcinoma, and their prevalence in associated lichen sclerosus lesions. RESULTS: In recent years several markers have been implicated as precursor markers for malignant transformation of lichen sclerosus into squamous cell carcinoma, including p53, Ki-67, γ-H2AX, MCM3 and cyclin D1. These proteins are up-regulated in lichen sclerosus of the vulva/penis and squamous cell carcinoma. Various levels of evidence show an association between lichen sclerosus and squamous cell carcinoma. p16 is over expressed in penile and vulvar squamous cell carcinoma associated with human papillomavirus infection but conflicting reports exist about its expression in lichen sclerosus. The angiogenesis markers vascular endothelial growth factor and cyclooxygenase-2 are expressed at higher levels, and microvessel density is increased in vulvar lichen sclerosus and squamous cell carcinoma, indicating a possible similar association in penile lichen sclerosus. CONCLUSIONS: Only a minority of lichen sclerosus cases are associated with squamous cell carcinoma. However, the therapeutic implications of a squamous cell carcinoma diagnosis are severe. Clinically, we lack an understanding of how to separate indolent lichen sclerosus cases from those in danger of progression to squamous cell carcinoma. Several protein markers show promise for further delineating the pathobiology of lichen sclerosus and the potential malignant transformation into squamous cell carcinoma.

Asunto(s)

Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/patología , Transformación Celular Neoplásica , Liquen Escleroso y Atrófico/patología , Neoplasias del Pene/patología , Liquen Escleroso Vulvar/patología , Neoplasias de la Vulva/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino