Special Issue "HPV in the Head and Neck Region 2.0".

Members of the human papillomavirus (HPV) family have been known for causing cancers and condylomas in the anogenital tract for some time, as reflected by the Nobel Prize in Medicine given to Professor Harald zur Hausen 2008 [...].

Sexually Transmitted Human Papillomavirus: Update in Epidemiology, Prevention, and Management.

This review presents the epidemiology, pathophysiology, prevention, and management of sexually transmitted human papillomavirus (HPV) and its associated diseases. HPV is the most common sexually transmitted infection worldwide. Prevalence varies regionally. Low-risk strains cause anogenital warts, which can be managed with patient- or provider-applied therapies. High-risk strains cause lower anogenital cancers. Primary and secondary prevention strategies include vaccination and screening for precancerous lesions, respectively. Management of abnormal screening results vary by test result, anatomic site, and individual cancer risk. Approaches include close rescreening, high-resolution visualization with biopsy, and-when biopsy-proven precancer is identified-removal or destruction of the lesion.

Bladder squamous cell carcinoma in situ in the background of condyloma acuminatum in a kidney transplant recipient.

Condyloma acuminatum with synchronous squamous cell carcinoma in situ (CIS) rarely occurs in the bladder. In developed countries, bladder squamous cell carcinoma (SCC) is uncommon. Among the various noninvasive squamous bladder lesions, there is significant morphological overlap, which further complicates accurate diagnosis. Immunosuppression and human papilloma virus increase the risk of bladder condyloma acuminatum, which has a strong association with bladder SCC. Herein, we describe a case of a 79-year-old man with a history of end-stage renal disease with kidney transplantation and anal SCC who presented with bladder squamous cell CIS arising in the background of condyloma acuminatum.

Condyloma acuminata: An evaluation of the immune response at cellular and molecular levels.

Condyloma acuminata (CA) is a benign proliferative disease mainly affecting in non-keratinized epithelia. Most cases of CA are caused by low-risk human papillomavirus (HPV), mainly HPV 6 and 11. The aim of the current study was to highlight the candidate genes and pathways associated with immune alterations in individuals who did not spontaneously eliminate the virus and, thus, develop genital warts. Paraffin-embedded condyloma samples (n = 56) were analyzed by immunohistochemistry using antibodies against CD1a, FOXP3, CD3, CD4, CD8, and IFN-γ. The immunomarkers were chosen based on the evaluation of the innate and adaptive immune pathways using qPCR analysis of 92 immune-related genes, applying a TaqMan Array Immune Response assay in HPV 6 or HPV 11 positive samples (n = 27). Gene expression analysis revealed 31 differentially expressed genes in CA lesions. Gene expression validation revealed upregulation of GZMB, IFNG, IL12B, and IL8 and downregulation of NFATC4 and IL7 in CA samples. Immunohistochemical analysis showed increased FOXP3, IFN-γ, CD1a, and CD4 expression in CA than in the control tissue samples. In contrast, CD3 and CD8 expression was decreased in CA lesion samples. Increased levels of pro-inflammatory cytokines in HPV-positive patients compared with HPV-negative patients seem to reflect the elevated immunogenicity of HPV-positive CA lesions. Host defense against HPV begins during the early stages of the innate immune response and is followed by activation of T lymphocytes, which are mainly represented by CD4+ and regulatory T cells. The low CD8+ T cell count in CA may contribute to this recurrent behavior. Additional studies are needed to elucidate the mechanism of host defense against HPV infection in CA.

Updated estimate of the annual direct medical cost of screening and treatment for human papillomavirus associated disease in the United States.

The annual direct medical cost attributable to human papillomavirus (HPV) in the United States over the period 2004-2007 was estimated at $9.36 billion in 2012 (updated to 2020 dollars). The purpose of this report was to update that estimate to account for the impact of HPV vaccination on HPV-attributable disease, reductions in the frequency of cervical cancer screening, and new data on the cost per case of treating HPV-attributable cancers. Based primarily on data from the literature, we estimated the annual direct medical cost burden as the sum of the costs of cervical cancer screening and follow-up and the cost of treating HPV-attributable cancers, anogenital warts, and recurrent respiratory papillomatosis (RRP). We estimated the total direct medical cost of HPV to be $9.01 billion annually over the period 2014-2018 (2020 U.S. dollars). Of this total cost, 55.0% was for routine cervical cancer screening and follow-up, 43.8% was for treatment of HPV-attributable cancer, and less than 2% was for treating anogenital warts and RRP. Although our updated estimate of the direct medical cost of HPV is slightly lower than the previous estimate, it would have been substantially lower had we not incorporated more recent, higher cancer treatment costs.

Successful treatment of anogenital warts with single dose Bacillus Calmette Guerin vaccine without prior sensitization in tuberculosis endemic country: Two case report.

Anogenital Warts (AGWs) are benign proliferations caused by Human Papillomavirus (HPV) infection on the genital or anal areas. Various therapeutic options are available for the treatment of AGWs but there is no best or ideal therapy, and the recurrence of AGWs is significantly high. A promising new therapy that is currently being evaluated is immunotherapy with the intralesional Bacillus Calmette-Guérin (BCG) vaccine. Two cases of a 23-year-old woman and a 41-year-old man were presented with manifestations of condyloma acuminata type AGWs. The patients were immunocompetent and received single dose intralesional BCG vaccine on the largest lesion. Clinical improvements of AGWs lesions were noted starting on the 14th day after receiving therapy by the disappearance of some lesions with no recurrence and side effects. Intralesional BCG vaccine activates the immune system, treats other AGWs lesions that do not receive an intralesional injection, and also prevents recurrence. Although the intralesional BCG vaccine is effective for treating AGWs, further evaluation is still needed for its recurrence.

Epidemiology of human papillomavirus on condyloma acuminatum in Shandong Province，China.

Condyloma acuminatum (CA) is a sexually transmitted disease (STD) caused by human papillomavirus (HPV) infection. It is important to study the prevalence and distribution of HPV genotypes before implementing the HPV vaccination program. Therefore, the aim of this study was to evaluate the epidemiological characteristics of CA cases and the distribution of HPV genotypes in Shandong Province, China. One-to-one questionnaire surveys were conducted on all patients diagnosed with CA in sentinel hospitals from Shandong Province, China. HPV genotypes were determined using the polymerase chain reaction (PCR)-reverse dot blot hybridization method. The study enrolled 1185 patients (870 males and 315 females) and found that CA patients are mainly males and sexually active people between the ages of 20 and 40. Recurrence occurred in 34.7% patients. Among the 880 CA patients who underwent HPV typing, the HPV test positivity rate was 91.4%. In these cases, low-risk (LR) HPV infection was predominant, with an infection rate of 91.3%, while high-risk (HR) HPV genotypes were found in 53.5% patients. The most frequent HPV genotypes encountered were HPV6 (57.8%), HPV11 (37.2%), HPV16 (13.7%), and HPV42 (10.3%). HPV6 and/or HPV11 are the main infections in all patients, and more than half of the patients are coinfected with HR-HPV. However, unlike other regions, HPV42 has a higher prevalence rate among CA patients in Shandong Province and is a nonvaccine HPV genotype. Therefore, regular HPV typing helps to understand the characteristics of specific genotypes and the choice of the best type for vaccine coverage.

The Efficacy of Cryotherapy and Zinc Gluconate in Management of Anogenital Warts: A Randomized Double-Blind, Split-Side, Placebo-Controlled Trial.

Anogenital warts are the most common sexually transmitted infection causing economic and psychosocial issues. Efficacy of zinc has been proved in treating nongenital warts, but its role in treating anogenital warts is not clear. This study was conducted to assess whether oral zinc gluconate in combination with cryotherapy effectively treated anogenital warts. A randomized double-blind, split-side, placebo-controlled trial was conducted on 50 patients suffering from genital warts. The patients were treated for 2 months with a combination of four sessions of cryotherapy and oral zinc gluconate versus placebos. Follow-up was performed at every 2 weeks based on the number of warts. The number of genital warts reduced significantly in both groups during treatment with cryotherapy, but no significant differences were observed between treatment with zinc and placebo. Patients in the zinc gluconate group reported significantly higher gastrointestinal adverse effects than those in the placebo group. This indicates that using oral zinc gluconate appeared to have no significant advantage over placebo in treating and reducing the number of genital warts; however, a longer duration of follow-up and pre-intervention serum level of zinc were necessary to evaluate the role of oral zinc therapy. (SKINmed. 2023;21:21-26).

Verrucous Carcinoma Arising in an Extended Giant Condyloma Acuminatum.

A 43-year-old heterosexual Tunisian man presented to the dermatology department with complaints of a genital friable mass. He had a past medical history of chronic hepatitis B. He was married and had a history of multiple sexual partners. The lesion had been present for over 10 years and gradually increased in size, disfiguring his genitalia. It had a major impact on his quality of life, preventing sexual intercourse and resulting in poor personal hygiene. On physical examination, the vegetative lesion presented as a giant cauliflower-like tumor (Figure 1) with a foul smell. The tumor involved the left inguinal region, the suprapubic genitalia, and was encircling the entire penile shaft. He also had inguinal lymphadenopathies. Under local anesthesia, a skin biopsy of the vegetative tumor was performed and sent for histopathologic examination. It revealed an exophytic epithelial tumor with papillomatosis, marked acanthosis, and many koilocytes, especially in the superficial layers of the epidermis. These signs along with the preservation of regular cytology were consistent with the diagnosis of condyloma acuminatum (Figure 2a). The histologic examination also showed clusters of atypical keratinocytes with high mitotic activity and keratinization, suggesting nests of squamous cell carcinoma (SCC) (Figure 2b and 2c). DNA-polymerase chain reaction (PCR) marker for Human papilloma virus (HPV) stains 11 was positive. Serology for hepatitis C, HIV, and syphilis non-reactive. Computed tomography scan of the abdomen and pelvis showed inguinal lymphadenopathies. The patient was referred to the oncologist for radiotherapy to reduce the size of the tumor followed by surgery. (SKINmed. 2023;21:53-54).

Evaluation of the optimal sampling approach for HPV genotyping in circumcised heterosexual men with genital warts.

BACKGROUND: Human papillomavirus (HPV) causes a serious socioeconomic burden globally. However, there is currently no consensus on the optimal sampling method for HPVDNA genotyping in circumcised heterosexual men. This study aimed to determine the diagnostic efficacy of 6 different anatomic sampling sites in HPV DNA polymerase chain reaction (PCR) testing of circumcised heterosexual men with genital warts. METHODS: The study included circumcised heterosexual men who presented to our clinic with complaints of genital warts. Swab samples were obtained from the penile shaft (PS), scrotum, coronal sulcus (CS), and external urethral meatus (EUM). First-void urine (FVU) and genital wart biopsy (GWB) were also tested for HPV DNA by PCR. RESULTS: A total of 32 patients (mean age: 36.9 ± 6.9 years) were included. None of the six samples studied was sufficient on its own to reveal all HPV types detected in a patient. When the samples were analyzed individually, GWB detected an average of 49.5% of total HPV types in a patient. This rate was 50.5% for PS, 40.4% for CS, 31.6% for scrotum, 26.3% for EUM, and 15.8% for FVU samples. The detection rate increased to 75.8% with combined testing of GWB and PS samples, 83.2% with GWB/PS/CS, 90.5% with GWB/PS/CS/scrotum, and 98.9% with GWB/PS/CS/scrotum/EUM samples. CONCLUSION: No single anatomic region or sample type can detect all HPV types present in circumcised heterosexual men by PCR assay. The detection rate approaches 99% when wart biopsy is combined with swab sampling of the penile shaft, coronal sulcus, scrotum, and external urethral meatus.

Trends of genital wart in Korea according to treatment method classification: Big data analysis of health care in 2010-2019.

PURPOSE: The purpose of this study is to investigate disease trend of genital wart through changes in each treatment method over the past 10 years in Korea. MATERIALS AND METHODS: From 2010 to 2019, surgical treatment including cauterization, excision, cryotherapy, and laser therapy, non-surgical treatment such as podophyllin, and surgical treatment for anorectal lesion were extracted and analyzed from 2010 to 2019. For each treatment method, characteristics such as sex, age, region, medical cost and average number of procedures were analyzed. RESULTS: The number of patients following all treatment modalities increased every year. Surgical treatment of genital wart and anorectal wart showed a significant increase in male patients. Number of non-surgical treatment decreased in males but increased in females. Surgical removal of the anorectal wart increased more than 250% in over 10 years, and males underwent surgery 4 times more than females. In both surgery and non-surgery, the mean session was higher in males. Most of them were carried out in primary medical institutions. In Seoul and Gyeonggi-do, the largest number of patients received treatment regardless of treatment method. CONCLUSIONS: Treatment for genital warts has increased rapidly over the past 10 years, and the increase in males is remarkable. The main treatment was surgery, and males mainly received surgical treatment, and females mainly received drug treatment. The primary medical institution was in charge of the most treatment. As the number of patients and related medical expenses are increasing rapidly, more attention and response to diseases are needed.

Downregulation of Sonic hedgehog signaling induces G2-arrest in genital warts.

BACKGROUND: Human papillomavirus (HPV) infected keratinocyte dysfunction results in the formation of genital warts, and the specific role of Sonic hedgehog (SHh) signaling in genital warts remains elusive. Thus, this study aimed to identify the correlation between wart formation and SHh signaling. MATERIALS AND METHODS: In this study, nine male patients with genital warts were recruited, and the expression of SHh and its downstream signal molecules Patched-1 and GLI family zinc finger 1 (Ptch1 and Gli1) was detected. Moreover, G2-phase cells in the collected genital warts samples were assessed with normal foreskin samples as a comparison. HPV6/11 were detected via in situ hybridization (ISH), and SHh expression of the corresponding paraffin sections was determined via immunohistochemical staining (IHC). In addition, an in vitro down-regulated SHh model was constructed by siRNA transfection of the HaCaT cell line, and the cell cycle was detected at 36 h by flow cytometry with propidium iodide staining. RESULTS: SHh, Ptch1, and Gli1 in warts were significantly downregulated in the condyloma acuminatum (CA) group compared to the normal foreskin group. G2-phase cells in the middle section of the spinous layer of CA wart tissues were significantly increased. Moreover, the expression of HPV-DNA was amplified and negatively correlated with SHh activity in CA wart tissues. Lastly, the downregulation of SHh-induced G2 arrest in vitro. CONCLUSIONS: The downregulation of the SHh signaling promotes HPV replication and the formation of warts by inducing G2/M arrest in the keratinocytes of CA.

5-aminolevulinic acid photodynamic therapy combined with wart curettage treatment for intractable urethral condylomata acuminata. A case report.

Condylomata acuminata (CA) is caused by human papillomavirus (HPV). It is one of the most common sexually transmitted diseases (STD). The lesions mainly occur in the external genitalia and perianal areas, rarely involves in urethral and usually localized at the distal 3 cm of the urethral orifice. Because of the special anatomical site, treating urethral CA is challenging and it has high recurrence rate after treatment. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) can successfully treat urethral CA, however, the experience of using ALA-PDT combined with wart curettage to treat intractable urethral CA is still very limited. In here, we reported an intractable urethral CA case with effective remission after receiving combination therapy. Wart curettage combine with ALA-PDT is an expeditious, economical, and well-tolerated treatment method.