Penile Intraepithelial Neoplasia Research Articles

Squamous Cell Carcinoma In Situ-The Importance of Early Diagnosis in Bowen Disease, Vulvar Intraepithelial Neoplasia, Penile Intraepithelial Neoplasia, and Erythroplasia of Queyrat.

Cutaneous squamous cell carcinoma (cSCC) is the second-most-prevalent malignancy in humans. A delayed diagnosis of cSCC leads to heightened invasiveness and positive surgical margins. Bowen's disease (BD) represents an early form of cSCC and presents as a small erythematous, photo-distributed, psoriasiform plaque. Although certain dermoscopy features in BD are quite characteristic, histopathology remains the gold standard for diagnosis and provides a severity-scoring system that assists in guiding appropriate treatment strategies. The classification of precancerous lesions of the vulva and penis has undergone multifarious transformations due to variations in clinical and histopathological characteristics. Presently, erythroplasia of Queyrat is categorized as a clinical variant of penile intraepithelial neoplasia (PeIN). The diagnoses of vulvar intraepithelial neoplasia (VIN) and PeIN present significant challenges and typically necessitate one or more biopsies, potentially guided by dermoscopy. Aceto-white testing demonstrates a notably high negative predictive value for genital precancerous lesions. Histopathological examination represents the gold-standard diagnosis in VIN and PeIN, while p16 and p53 immunostainings alongside HPV testing provide crucial diagnostic clues. The histopathologic features, degree of differentiation, and associations with lichen planus, lichen sclerosus, and HPV guide the selection of conservative treatments or surgical excision.

Penile intraepithelial neoplasia incidence, clinical classification, microenvironment and implications for imiquimod treatment.

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. 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. 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. 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.

Characteristics, trends, and management of Penile cancer in the United States: A population-based study

BackgroundPenile cancer (PeCa) is a rare disease. HPV infection, smoking, phimosis, and lichen sclerosus represent well-known associated risk factors. ObjectivesPrimary aim of our study is to evaluate the incidence and risk factors of PeCa and to outline the adopted diagnostic and therapeutic approaches. Secondary aim is to investigate risk factors associated with aggressive disease and to identify the complications arising from its surgical treatment. Materials and MethodsWe conducted a retrospective analysis using the PearlDiver™ Mariner database, from January 1, 2011, to December 31, 2021, identifying all patients diagnosed with PeCa and PeIN, evaluating comorbidities, risk factors, and social and economic conditions. We evaluated the imaging modalities employed for staging as well as the treatment strategies. Finally, we evaluated the most frequent complications associated with inguinal lymphadenectomy (ILND). ResultsDuring the study period, 17,494 patients were diagnosed with PeCa and 5,965 with penile intraepithelial neoplasia (PeIN). US was the most frequently utilized imaging modality, followed by PET and PET/CT. Use of CT and MRI was around 5%. Surgical treatment was the predominant strategy, utilized in 31.3% of PeCa and 22.9% of PeIN. Wide Local Excision/Glansectomy emerged as the most common surgical procedures. MLR analysis identified smoking as a risk factor for metastatic PeCa (OR; 95% CI = 1.49; 1.379–1.609), HPV infections were associated with a 35% decrease in risk (OR; 95% CI = 0.65; 0.562–0.744) (all P < 0.001). Lichen sclerosus and phimosis were associated with a doubled risk of demolitive surgery. Approximately 40% of patients experienced complications associated with ILND. ConclusionDespite advances in PeCa management, there's no significant move toward more conservative treatments. Surgical treatments are still marked by high rates of complications, potentially affect the sexual and psychosocial health of patients. These issues may foster a tendency toward avoidance behaviors, contributing to a delayed clinical presentation and treatment.

Retrospective Cross-Sectional Epidemiological Study of Human Papillomavirus-Associated Precancers and Anogenital Warts in Patients Attending Specialized Clinics in Russian Federation

Background. In Russia, there are no country level registries on HPV-associated pre-cancers (cervical intraepithelial neoplasia, CIN; vulvar intraepithelial neoplasia, VIN; vaginal intraepithelial neoplasia, VaIN; anal intraepithelial neoplasia, AIN; penile intraepithelial neoplasia PIN) and anogenital warts (AWs) and no national-level cervical cancer screening program. Aims — the aim of this study was to assess the proportion of patients with CIN, VIN, VaIN, AIN, PIN and AWs diagnosis in the clinical settings in Russia. Methods. This study was a non-interventional retrospective multi-center chart-review study in 28 investigational sites representing 21 Federal subjects of 6 Federal Districts of Russia. Medical charts of adult men and women visited gynecology, sexual health, dermatovenerology or urology services between 1 Jan 2000 — 31 Dec 2019 were reviewed. Data were abstracted, using a standardized approach, on patient demographic characteristics, presence or absence of pre-cancers and AWs diagnoses, method of diagnosing pre-cancer and HPV infection, and grade of neoplasia. Results. A total of 11 520 patients (1732 male and 9788 female) were included in the analysis. The overall proportion of patients with HPV-associated precancers and AWs was 10.8%. By service type, cases of HPV-associated conditions were revealed most often in dermatological departments (14.5%) and gynecological hospitals (13.8%). CIN detection rate in Russian clinical settings increased over the 20-years from 3.2 to 11.1% and was higher in gynecological in-patient departments compared to out-patient departments (12.5 and 5.2% respectively). The number of non-cervical precancers (VIN, VaIN, AIN, PIN) cases were very low (the detection rate was less than 1%). The frequency of HPV type 16 and 18 detection increased from 0.6 to 4.8%, and from 0.2 to 1.9%, respectively, for the 20-years period. Conclusions. Our study suggested high level of HPV-related pre-cancer and AW disease burden as well as presence of high-risk HPV types. Preventive strategy through effective national HPV immunization program would be beneficial to reduce HPV-related disease burden in Russia.

UrethroNAV: the aetiology and extent of idiopathic urethral stricture in an Australian population.

Lichen sclerosus (LS) is considered a causative factor in 10% of cases of idiopathic urethral stricture disease (IUSD), which is important for determining management strategies due to the underlying pathophysiology. Traditional excision urethroplasty may not be effective as inflammation often extends beyond the macroscopic stricture. This pilot study aims to answer two research questions: is LS an underlying cause of some idiopathic cause of strictures, and, if there is histological evidence suggesting predisposition of the surrounding tissue to strictures. Biopsies were taken from the stricture site as well as 1 and 2 cm proximal and distal in patients with IUSD. Histological features, including macroscopic and microscopic findings, were reported, including the presence of LS, hyperkeratosis, epidermal changes, lichenoid infiltrates, ulceration, scarring, and inflammation. Methylene blue was used to aid in locating damaged urothelium. Patients were prospectively followed up after urethroplasty. From 109 urethroplasties performed between 2019 to 2022, 15 male patients were enrolled after meeting specific inclusion criteria. These criteria included a diagnosis of IUSD and the absence of any evidence of trauma, macroscopic inflammatory disease, or previous endoscopic instrumentation of the urethra. Patients had to be at least 16 years old and medically suitable for undergoing urethroplasty. The study was approved by the hospitals ethics committees. None had macroscopic evidence of LS. One patient had microscopic evidence of LS at the 2 cm proximal biopsy only. A total of 93% of patients had scarring proximal and distal to the stricture, while 20-40% had inflammatory change. The patient with microscopic LS and two inflammatory change patients had stricture recurrence after urethroplasty. Additionally, one patient with inflammatory changes was diagnosed with penile intraepithelial neoplasia (PeIN) and underwent partial penectomy. Findings suggest that an underlying cause of IUSD could be LS. Additionally, the pathophysiology may involve scarring and inflammation beyond the limits of the stricture with extension distal from the stricture site. Careful evaluation for concomitant urethral pathology should be considered in cases of inflammatory changes. These findings should be considered in the surgical management of IUSD and warrant further research into the role of routine biopsy and drug targets in USD.

A comprehensive review of current knowledge on penile squamous cell carcinoma.

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.

Penile Intra-epithelial Neoplasia (PeIN) positive margin in men treated with surgery for invasive Squamous Cell Carcinoma (SCC) or PeIN: Do we need to worry?

Penile Intra-epithelial Neoplasia (PeIN) positive margin in men treated with surgery for invasive Squamous Cell Carcinoma (SCC) or PeIN: Do we need to worry?

The Spectrum of HPV-independent Penile Intraepithelial Neoplasia: A Proposal for Subclassification.

Compared with vulva, precursor lesions of human papillomavirus (HPV)-independent invasive squamous cell carcinoma (SCC) of the penis are insufficiently characterized. We analyzed the histologic and immunohistochemical characteristics of 70 peritumoral precursor lesions and correlated them with the histology and mutational profile of the adjacent HPV-negative invasive penile SCC. Atypical basal keratinocyte proliferation with variously elongated epithelial rete with premature squamatiziation, but regular superficial cornification, termed differentiated penile intraepithelial neoplasia (d-PeIN), were identified adjacent to 42/70 (60%) SCC (36/42 keratinizing (P<0.001); 3 papillary, and 1 each verrucous, clear cell, sarcomatoid SCC). d-PeIN were associated with chronic inflammatory dermatoses (32/42; P<0.001), p53 overexpression (26/42; P<0.001), and hotspot mutations in TP53 (32/42; P<0.001), CDKN2A (26/42; P<0.001) or both (21/42; P=0.003) in the adjacent SCC. Cytoplasmic p16ink4a overexpression in 5/42 d-PeIN correlated with CDKN2A missense mutations in the adjacent SCC. In all, 21/70 (30%) cornified verrucous or glycogenated verruciform precursors with minimal atypia and wild-type p53 (18/21; P<0.001) occurred adjacent to verrucous or papillary SCC (17/21; P<0.001) and keratinizing (4/21) SCC, which harbored mutations in HRAS and/or PIK3CA (12/21; P<0.004). Undifferentiated p16ink4a-negative full-thickness precursors were identified in 7/70 (10%) SCC. Four histologically different HPV-independent penile precursor lesions can be assigned to 2 major genetic/biological pathways with characteristic highly differentiated precursors requiring different clinical management decisions. These include d-PeIN in chronic inflammatory dermatoses, with p53 overexpression and TP53/CDKN2A mutations, and the p53 wild-type verrucous and verruciform precursors unassociated with dermatoses, but with mutations in oncogenes PIK3CA and HRAS.

Risk of Local Recurrence in Men With Penile Intraepithelial Neoplasia in the Surgical Margin After Penile-sparing Surgery.

Up to 90% of men with a positive surgical margin show remaining cancer in subsequent reresections. The risk of local recurrence in men with no penile cancer but the precancerous lesion penile intraepithelial neoplasia at the surgical margin is less well studied and was the aim of this analysis. This was a retrospective analysis of men with distal penile cancer undergoing penile-sparing surgery. A competing risks survival analysis adjusted for grade, lymphovascular invasion, and stage was performed to assess local recurrence-free survival in patients with penile intraepithelial neoplasia-positive margins and completely negative surgical margins. A negative surgical margin was described in 319 men (85%), whereas penile intraepithelial neoplasia in the surgical margin was found in 59 men (15%). Local recurrence was observed in 30/319 men with a negative surgical margin compared to 11/59 men with penile intraepithelial neoplasia in the surgical margin. Adjusted for T stage and grade, patients with penile intraepithelial neoplasia at the surgical margin had a higher risk to develop a local recurrence than those with a negative surgical margin without penile intraepithelial neoplasia (HR 1.51, 95% CI 1.07-2.12, P = .019). Men with a penile intraepithelial neoplasia-positive surgical margin have an increased risk to experience local recurrence compared to men with a negative surgical margin and should undergo closer surveillance and/or adjuvant treatment.

Impact of Human Papillomavirus Vaccination on Male Disease: A Systematic Review.

Human papillomavirus (HPV)-related diseases are highly prevalent in men worldwide, comprising external anogenital condyloma, anal intraepithelial neoplasia (AIN), penile intraepithelial neoplasia (PIN), and anogenital and oropharyngeal cancers. There is exceptionally low vaccine coverage in the male population. Only 4% of men were fully vaccinated, worldwide, as of 2019. The aim of this review is to assess the impact of HPV vaccination on male disease. Three databases (MEDLINE, Web of Science, Scopus) and Clinical Trials.gov were searched. We included thirteen studies, eight randomized controlled trials (RCTs), and five cohorts, comprising a total of 14,239 participants. Regarding anal disease, seven studies reported HPV vaccine efficacy ranging from 91.1% to 93.1% against AIN1, and ranging from 89.6% to 91.7% against AIN2|3 and anal cancer. Five studies showed an efficacy against genital condyloma of 89.9% in HPV-naïve males, varying between 66.7% and 67.2% in intention-to-treat populations. Studies reporting no efficacy have included older participants. These results support vaccination of young men previously infected, beyond HPV-naïve males. The evidence quality was moderate to low for most outcomes, namely genital diseases. RCTs are needed to assess the efficacy of HPV vaccination on male oropharyngeal cancer.

Real-world treatment outcomes of patients with penile cancer in the Kyushu-Okinawa area of Japan in the pre-guideline era.

To understand the real-world outcomes for patients with penile cancer in the Kyushu-Okinawa area before the introduction of practice guidelines in Japan. We retrospectively collected medical information on patients with penile squamous cell carcinoma and penile intraepithelial neoplasia at 12 university hospitals and their affiliated hospitals in the Kyushu-Okinawa area from January 2009 to December 2020. Patients with unknown clinical stage were excluded. Patient background characteristics and survival, as well as pretreatment factors involved in survival, were investigated. A total of 196 patients were included. Patients with clinical stage 0, I, IIA, IIB, IIIA, IIIB and IV comprised 9.7, 26.0, 22.4, 2.6, 10.7, 14.3 and 14.3%, respectively. The median follow-up was 26months, and the mean 5-year overall survival and cancer-specific survival rates were 74.3 and 79.8%, respectively. On univariate analysis, tumor diameter≥30mm, penile shaft tumor, Eastern Cooperative Oncology Group performance status≥1, cT≥3, cN≥2 and cM1 were associated with significantly poorer cancer-specific survival. On multivariate analysis, pretreatment factors of cN≥2 (hazard ratio, 32.5; 95% confidence interval, 5.08-208; P=0.0002), Eastern Cooperative Oncology Group performance status≥1 (4.42; 1.79-10.9; P=0.0012) and cT≥3 (3.34; 1.11-10.1; P=0.0319) were identified as independent prognostic factors. The study revealed basic data for future penile cancer treatment and research, including survival rates according to clinical stages, and identified cN≥2, Eastern Cooperative Oncology Group performance status≥1 and cT≥3 at initial diagnosis as independent prognostic factors. Evidence for penile cancer in Japan is particularly scarce, and future large-scale prospective studies are warranted.

Human Papillomavirus 16 Lineage A Variants Associated With Persistent Genital Infections in Men: The HPV Infection in Men (HIM) Study.

Human papillomavirus (HPV) 16 non-A lineage variants have higher carcinogenic potential for cervical cancer. HPV-16 variants natural history among males is not established. We evaluated HPV-16 variants prevalence and persistence in the external genitalia of men enrolled in the prospective HPV Infection in Men (HIM) Study. The HIM Study included men from the United States, Brazil, and Mexico. HPV-16 variants were distinguished using polymerase chain reaction sequencing. The prevalence of HPV-16 variants was assessed, and associations with infection persistence were estimated. We characterized the HPV-16 variants for 1700 genital swab samples from 753 men and 22 external genital lesions in 17 men. The prevalence of HPV-16 lineages differed by country and marital status (P < .001). Overall, 90.9% of participants harbored lineage A variants. The prevalence of non-A lineages was heterogenous among countries. HPV-16 lineage A variants were associated with a 2.69-fold increased risk of long-term persistent infections compared with non-A lineages. All high-grade penile intraepithelial neoplasia harbored lineage A variants and occurred in the context of long-term persistent infections with the same variants. The prevalence and persistence of HPV-16 variants observed at the male external genitalia suggest differences in the natural history of these variants between men and women, which may be associated with intrinsic differences in the infected genital epithelia.

Proteomic and Clinicopathologic Assessment of Penile Amyloidosis: A Single Institutional Review of 12 Cases.

There is a paucity of data on penile amyloidosis. We aimed to assess the frequency of different amyloid types in surgical specimens from the penis involved by amyloidosis and correlate relevant clinicopathologic parameters with proteomic findings. Since 2008, our reference laboratory has performed liquid chromatography/tandem mass spectrometry (LC-MS/MS) for amyloid typing. The institutional pathology archive and reference laboratory database were queried to retrospectively identify all penile surgical pathology specimens with LC-MS/MS results between January 1, 2008, and November 23, 2022. Archived H&E-stained and Congo red-stained sections were re-reviewed. Twelve cases of penile amyloidosis were identified, which represented 0.35% (n = 3,456) of penile surgical specimens. AL-type amyloid was most frequent (n = 7), followed by keratin-type amyloid (n = 3) and ATTR (transthyretin)-type amyloid (n = 2). AL-type amyloid cases often showed diffuse dermal/lamina propria deposition, whereas all keratin-type amyloid cases were localized to the superficial dermis. Two cases with keratin-type amyloid had concomitant cutaneous findings (penile intraepithelial neoplasia and condyloma). This series, the largest to date, demonstrates that penile amyloidosis has a heterogeneous proteomic landscape. To the best of our knowledge, this is the first study describing ATTR (transthyretin)-type penile amyloid.

1044 Transcriptionally active human papillomavirus (HPV) in male genital lichen sclerosus (MGLSc), penile intraepithelial neoplasia (PeIN), and penile squamous cell carcinoma (PeSCC)

1044 Transcriptionally active human papillomavirus (HPV) in male genital lichen sclerosus (MGLSc), penile intraepithelial neoplasia (PeIN), and penile squamous cell carcinoma (PeSCC)

MP50-02 RISK OF LOCAL RECURRENCE IN MEN WITH PENILE INTRAEPITHELIAL NEOPLASIA (PEIN) IN THE SURGICAL MARGIN AFTER PENILE SPARING SURGERY

You have accessJournal of UrologyCME1 Apr 2023MP50-02 RISK OF LOCAL RECURRENCE IN MEN WITH PENILE INTRAEPITHELIAL NEOPLASIA (PEIN) IN THE SURGICAL MARGIN AFTER PENILE SPARING SURGERY Luca Antonelli, Esther W. C. Lee, Allaudin Issa, James Churchill, Pedro Oliveira, Maurice Lau, Vijay Sangar, Arie Parnham, and Christian D. Fankhauser Luca AntonelliLuca Antonelli More articles by this author , Esther W. C. LeeEsther W. C. Lee More articles by this author , Allaudin IssaAllaudin Issa More articles by this author , James ChurchillJames Churchill More articles by this author , Pedro OliveiraPedro Oliveira More articles by this author , Maurice LauMaurice Lau More articles by this author , Vijay SangarVijay Sangar More articles by this author , Arie ParnhamArie Parnham More articles by this author , and Christian D. FankhauserChristian D. Fankhauser More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003298.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Early detection and treatment of local recurrence after penile sparing surgery is crucial as 10% of men with local recurrence develops metastatic disease. An important risk factor for local recurrence represents a positive surgical margin as 90% of men with a positive surgical margin show remaining cancer in subsequent reresections. The risk of local recurrence in men with no penile cancer but the precancerous lesion penile intraepithelial neoplasia (PeIN) in the surgical margin is less well studied and was the aim of this analysis. METHODS: Retrospective analysis of men with distal penile cancer undergoing penile-sparing surgery. Kaplan Meier curves and Log rank test and a multivariable Cox regression adjusted for grade and stage were performed to assess the difference of local recurrence free survival in patients with PeIN positive margins and completely negative margins. RESULTS: A negative surgical margin was described in 319 men (85%), whereas PeIN in the surgical margin was found in 59 men (15%). Local recurrence was observed 30/319 (9%) of men with a negative surgical margin compared to 11/59 (19%) men with PeIN in the surgical margin. After a median follow up of 2.8 years, patients with PeIN at the margin were more likely to have local recurrence than those with negative margins (log rank p=0.03). Adjusted for T stage and grade, patients with PeIN at the surgical margin had a higher risk to develop a local recurrence than those with negative surgical margins for PeIN (HR 2.17, p=0.03). CONCLUSIONS: Men with a PeIN in the surgical margin have twice as high a chance to experience a local recurrence compared to men with a negative surgical margin without PeIN. Men with PeIN in the surgical margin should undergo closer monitoring and adjuvant treatment options should be studied. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e685 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luca Antonelli More articles by this author Esther W. C. Lee More articles by this author Allaudin Issa More articles by this author James Churchill More articles by this author Pedro Oliveira More articles by this author Maurice Lau More articles by this author Vijay Sangar More articles by this author Arie Parnham More articles by this author Christian D. Fankhauser More articles by this author Expand All Advertisement PDF downloadLoading ...

Penile Intraepithelial Neoplasia: a Disease That Should Be Recognized.

Penile Intraepithelial Neoplasia: a Disease That Should Be Recognized.

Penile Intraepithelial Neoplasia (PeIN) in a young man with the clinical appearance of Buschke Lowenstein Tumor

Background: The incidence of penile cancer in the general population is rare. Epidemiologically, penile cancer occurs less than 1% compared to other types of cancer. Penile Intraepithelial Neoplasia (PeIN) is a precancerous lesion of invasive squamous cell carcinoma characterized by dysplastic changes of squamous epithelium with the intact basement membrane. This case report aims to increase understanding of Penile Intraepithelial Neoplasia (PeIN), especially with the clinical appearance of the Buschke Lowenstein Tumor, diagnosis, examination, and appropriate management. Case Presentation: A 21-year-old Balinese man presented with a lump on his genitalia without itching, pain, and a lesion that bleeds easily, which has appeared since January 2022. He complained that the lump was getting bigger and bigger. Physical examination showed multiple hyperpigmented papules and plaques with well-defined oval and corn shapes that vary in size with a dense consistency and a verrucous surface. Laboratory tests showed negative on Hep-B and HIV tests. The patient also had a biopsy of the lump where the results showed Penile Intraepithelial Neoplasia. The patient was treated with 6 cycles of TCA 80% once a week, but it did not improve, so circumcision and surgical excision were carried out on June 2022. Fourteen days after surgery, multiple lumps appeared, recurred, and increased in number and size. On 1-month observation after the second surgery, the patient denied complaints of the genitals. Venerological status was within normal limits. Conclusion: HPV-related Penile Intraepithelial Neoplasia (Warty subtype) with the clinical appearance of Buschke Lowenstein Tumor was reported in a 21-year-old Balinese man treated with Glans Resurfacing surgical excision with satisfactory results characterized by no functional abnormalities both during urination or erection.

Multi-center evaluation of morbidity and predictors of response to imiquimod treatment for penile intraepithelial neoplasia (PeIN)

Multi-center evaluation of morbidity and predictors of response to imiquimod treatment for penile intraepithelial neoplasia (PeIN)

Global research trends in penile cancer: Bibliometric and visualized analysis.

Penile cancer is a malignant tumor of the genitourinary system that mostly occurs in middle-aged and elderly men aged 50-70 years, which can seriously affect physical, psychological, and sexual health. Hundreds of original articles and reviews on penile cancer are published each year. However, a bibliometric analysis of these publications has not been performed. This study aimed to systematically analyze and visualize penile cancer-related publications through bibliometrics and reveal identified topics, hotspots, and knowledge gaps in related fields. Based on the Web of Science core collection database, we first analyzed the quantity and quality of publications in the field of penile cancer. Second, we profiled the publishing groups in terms of country, institution, author's publication, and cooperation network. Then, we systematized and summarized the hot topics of research. This bibliometric analysis was conducted from 2001 to 2022. The analysis identified 1,687 articles and reviews, which were published in 432 journals. The number of publications and citations on penile cancer-related research has steadily increased over the last two decades. Furthermore, academic institutions in Europe and the United States play a leading role in penile cancer research. The country, institution, journal, and author with the most publications were the United States (507), H Lee Moffitt Cancer Research Center (96), Journal of Urology (83), and Spiess P (87), respectively. The most frequently used keywords were penile cancer (743), squamous-cell carcinoma (717), cancer (380), carcinoma (232), lymphadenectomy (229). 16 keyword clustering information was obtained, including #0 male circumcision, #1 lichen sclerosus, #2 chemotherapy, #3 penile neoplasms, #4 targeted therapy, #5 resection margin, #6 cervical cancer, #7 lymph node dissection, #8 prognostic factor, #9 prostate cancer, #10 inguinal lymph node dissection, #11 human papillomavirus DNA, #12 gene, #13 penile intraepithelial neoplasia, #14 male sexual function, and #15 penile cancer. More and more scholars are devoted to the research on penile cancer. This bibliometric analysis revealed that the main research topics and hotspots in penile cancer included risk factors and surgical treatment plans.

Penile intraepithelial neoplasia: Distribution of subtypes, HPV genotypes and p16INK4a in 84 international cases

There are few pathologic or molecular studies of penile precancerous lesions, and the majority refers to lesions associated with invasive carcinomas. Penile Intraepithelial Neoplasia (PeIN) is classified in two morphologically and distinctive molecular groups, non-HPV and HPV-related with special subtypes. The primary purpose of this international series was to classify PeIN morphologically, detect HPV genotypes and determine their distribution according to PeIN subtypes. A secondary aim was to evaluate the p16INK4a immunostaining as a possible HPV surrogate for high-risk HPV infection in penile precancerous lesions. Samples consisted of 84 PeIN cases, part of a retrospective cross-sectional analysis of 1095 penile carcinomas designed to estimate the HPV DNA prevalence in penile cancers using PCR and p16INK4a immunostaining. Penile Intraepithelial Neoplasia (PeIN) was classified in HPV-related (basaloid, warty-basaloid, warty, hybrid, and mixed subtypes) and non-HPV-related (differentiated), the former being the most frequent. PeIN subtypes were differentiated (non-HPV-related) and basaloid, warty-basaloid, warty, hybrid and mixed (HPV-related). Basaloid PeIN was the most commonly diagnosed subtype, and HPV16 was the most frequent HPV genotype detected. Warty-basaloid and warty PeIN showed a more heterogeneous genotypic composition. Most HPV genotypes were high-risk but low-risk HPV genotypes were also present in a few cases (4%). A single HPV genotype was detected in in 82% of HPV positive cases. In contrast, multiple genotypes were detected in the remaining 18% of cases. The findings in this study support the paradigm that penile in situ neoplasia, like its invasive counterparts, is HPV dependent or independent and has distinctive morphological subtypes readily identified in routine practice. Considering that HPV16 is clearly the predominant type, and that the three available vaccines have HPV16, all of them will be suitable for vaccination programs; the price of the vaccines will be probably the main determinant to choose the vaccine.