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Journal of Clinical Medicine Feb 2022Human papillomavirus (HPV) infection drives tumorigenesis in almost all cervical cancers and a fraction of vulvar and penile cancers. Due to increasing incidence and low... (Review)
Review
Human papillomavirus (HPV) infection drives tumorigenesis in almost all cervical cancers and a fraction of vulvar and penile cancers. Due to increasing incidence and low vaccination rates, many will still have to face HPV-related morbidity and mortality in the upcoming years. Current treatment options (i.e., surgery and/or chemoradiation) for urogenital (pre-)malignancies can have profound psychosocial and psychosexual effects on patients. Moreover, in the setting of advanced disease, responses to current therapies remain poor and nondurable, highlighting the unmet need for novel therapies that prevent recurrent disease and improve clinical outcome. Immunotherapy can be a useful addition to the current therapeutic strategies in various settings of disease, offering relatively fewer adverse effects and potential improvement in survival. This review discusses immune evasion mechanisms accompanying HPV infection and HPV-related tumorigenesis and summarizes current immunotherapeutic approaches for the treatment of HPV-related (pre-)malignant lesions of the uterine cervix, vulva, and penis.
PubMed: 35207374
DOI: 10.3390/jcm11041101 -
Tropical Doctor Jan 2023Trichomoniasis is the most common non-viral sexually transmitted infection (STI) occurring worldwide and the majority of infected persons (70-85%) have mild or no...
Trichomoniasis is the most common non-viral sexually transmitted infection (STI) occurring worldwide and the majority of infected persons (70-85%) have mild or no genital symptoms. Symptoms in women may include a vaginal discharge which may be associated with vulval irritation and most infections can be effectively treated with metronidazole 500mg bd for seven days. Trichomoniasis unresponsive to 5-nitroimidazole therapy is uncommon but results in substantial therapeutic challenges, especially in resource limited countries. We present such a case which was eventually treated with a low-cost intravaginal combination of boric acid and clotrimazole cream.
Topics: Female; Humans; Trichomonas Vaginitis; Trinidad and Tobago; Trichomonas Infections; Metronidazole
PubMed: 36214266
DOI: 10.1177/00494755221131370 -
Pediatric Emergency Care Feb 2021We aimed to describe our experience in diagnosing and managing Lipschutz ulcers in children.
OBJECTIVE
We aimed to describe our experience in diagnosing and managing Lipschutz ulcers in children.
METHODS
This was a retrospective data review in a tertiary referral clinic for pediatric and adolescent gynecology. We identified patients referred with a vulval ulcer and recorded relating symptoms, presentation, and resolution.
RESULTS
We identified 7 nonsexually active girls with vulvar ulcers presenting within the course of an upper respiratory infection, including fever and cough. Average age was 12.25 years (range, 11-14.5 years). All patients presented with at least one large painful ulcer within the inner surface of the labium minor, of up to 2 cm in diameter.Initial presentation was of a bullous lesion that was then ulcerated, covered by a black gangrenous scab. Over the course of the week, the scab fell leaving a white-based ulcer that gradually healed. All children complained of dysuria stemming from contact irritation with urine. The ulcer gradually disappeared, leaving no mark within 10 days of initial presentation.Two of 7 patients presented with 3 similar recurrences after flu-like symptoms.None of the patients qualified for diagnosis of Behcet disease.
CONCLUSIONS
Lipschutz ulcers are painful genital lesions causing anxiety to the girl and her family. Pediatricians and gynecologists should be aware of the condition, diagnose it where appropriate, avoid unnecessary medication, and reassure the patient that it is self-limited.
Topics: Adolescent; Child; Female; Fever; Humans; Retrospective Studies; Ulcer; Vulvar Diseases
PubMed: 31977773
DOI: 10.1097/PEC.0000000000002004 -
Current Problems in Diagnostic Radiology 2022Female genital tuberculosis is a relatively uncommon form of extrapulmonary tuberculosis that is under-reported and under-recognized. The early course of the disease has... (Review)
Review
Female genital tuberculosis is a relatively uncommon form of extrapulmonary tuberculosis that is under-reported and under-recognized. The early course of the disease has fewer manifestations, resulting in late presentation with grave complications like infertility and ectopic pregnancy. Also, difficulty in isolation of the causative bacteria further delays the diagnosis. The radiologist should be well versed with imaging findings of female genital TB to help the clinicians to initiate prompt treatment. This review shall cover imaging findings of female genital TB involving fallopian tubes, uterus, ovaries, cervix, vagina, and vulva on different imaging modalities. Fallopian tubes are almost always involved in genital TB followed by uterus and ovaries. Hysterosalpingogram and ultrasound can best detect tubercular changes in fallopian tubes and uterus whereas cross-sectional imaging is essential for the diagnosis of ovarian or peritoneal TB as they closely mimic malignancy. Cervical, vaginal, or vulval TB produces nonspecific changes and histopathological diagnosis is required for confirmation of the diagnoses. Close differential diagnosis on imaging like malignancy or pelvic inflammatory disease, are also discussed with a brief discussion of the pathogenesis.
Topics: Fallopian Tubes; Female; Humans; Infertility, Female; Ovary; Pregnancy; Tuberculosis, Female Genital; Uterus
PubMed: 34304946
DOI: 10.1067/j.cpradiol.2021.06.014 -
International Journal of Dermatology Jan 2023Sodium-glucose co-transporter 2 (SGLT2) inhibitors, or gliflozins, are used as mono or combined therapy in the management of diabetes. Genital infections are the most...
INTRODUCTION
Sodium-glucose co-transporter 2 (SGLT2) inhibitors, or gliflozins, are used as mono or combined therapy in the management of diabetes. Genital infections are the most common reported adverse effect, as a result of induced glycosuria. Cutaneous features of patients experiencing vulval symptoms while on SGLT2 inhibitor therapy have not been clearly described in published literature. We have observed a specific inflammatory vulvitis with psoriasiform features in patients taking SGLT2 inhibitors, related to candidiasis in most cases.
METHODS AND RESULTS
Demographic and treatment outcomes of 11 patients with characteristic inflammatory changes after starting SGLT2 inhibitors were extracted from electronic records. Ninety-one percent (n = 10) had candidiasis, treated with fluconazole. Six (54.5%) were able to continue SGLT-2 inhibitors through the addition of topical treatments, but five patients had to discontinue the drug.
CONCLUSIONS
SGLT2 inhibitors can result in characteristic inflammatory vulvitis. Treatment with topical agents and single-dose antifungals may allow patients to continue their therapy to achieve improved glycemic control. In resistant cases, discontinuation of the drug is necessary. We highlight this effect so that early treatment can be initiated to alleviate symptoms and recognition of underlying cause.
Topics: Female; Humans; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Sodium-Glucose Transporter 2; Diabetes Mellitus, Type 2; Vulvitis; Candidiasis
PubMed: 36250299
DOI: 10.1111/ijd.16449 -
International Journal of Gynecological... Mar 2022Standard treatment of locally advanced gynecological cancers relies mainly on platinum-based concurrent chemoradiotherapy followed by brachytherapy. Current... (Review)
Review
Standard treatment of locally advanced gynecological cancers relies mainly on platinum-based concurrent chemoradiotherapy followed by brachytherapy. Current chemotherapeutic drugs are only transiently effective and patients with advanced disease often develop resistance and subsequently, distant metastases despite significant initial responses of the primary tumor. In addition, some patients still develop local failure or progression, suggesting that there is still a place for increasing the anti-tumor radiation effect. Several strategies are being developed to increase the probability of curing patients. Vaginal cancer and vulva cancer are rare diseases, which resemble cervical cancer in their histology and pathogenesis. These gynecological cancers are predominantly associated with human papilloma virus infection. Treatment strategies in other unresectable gynecologic cancers are usually derived from evidence in locally advanced cervical cancers. In this review, we discuss mechanisms by which novel therapies could work synergistically with conventional chemoradiotherapy, from pre-clinical and ongoing clinical data. Trimodal, even quadrimodal treatment are currently being tested in clinical trials. Novel combinations derived from a metastatic setting, and being tested in locally advanced tumors, include anti-angiogenic agents, immunotherapy, tumor-infiltrating lymphocytes therapy, adoptive T-cell therapy and apoptosis inducers to enhance chemoradiotherapy efficacy through complementary molecular pathways. In parallel, radiosensitizers, such as nanoparticles and radiosensitizers of hypoxia aim to maximize the effect of radiotherapy locally.
Topics: Brachytherapy; Chemoradiotherapy; Combined Modality Therapy; Female; Humans; Immunotherapy; Uterine Cervical Neoplasms
PubMed: 35256428
DOI: 10.1136/ijgc-2021-002529 -
Reviews in Medical Virology May 2022High-risk human papillomavirus (HR-HPV) infection is a necessary cause for the development of cervical cancer. Moreover, HR-HPV is also associated with cancers in the... (Review)
Review
High-risk human papillomavirus (HR-HPV) infection is a necessary cause for the development of cervical cancer. Moreover, HR-HPV is also associated with cancers in the anus, vagina, vulva, penis and oropharynx. HR-HPVs target and modify the function of different cell biomolecules, such as glucose, amino acids, lipids and transcription factors (TF), such as p53, nuclear factor erythroid 2-related factor 2 (Nrf2), among others. The latter is a master TF that maintains redox homeostasis. Nrf2 also induces the transcription of genes associated with cell detoxification. Since both processes are critical for cell physiology, Nrf2 deregulation is associated with cancer development. Nrf2 is a crucial molecule in HPV-related cancer development but underexplored. Moreover, Nrf2 activation is also associated with resistance to chemotherapy and radiotherapy in these cancers. This review focusses on the importance of Nrf2 during HPV-related cancer development, resistance to therapy and potential therapies associated with Nrf2 as a molecular target.
Topics: Alphapapillomavirus; Female; Humans; Male; NF-E2-Related Factor 2; Neoplasms; Papillomavirus Infections
PubMed: 34694662
DOI: 10.1002/rmv.2308 -
Journal of the American Academy of... Dec 2019Human papillomavirus (HPV) causes cervical cancer, anal cancer, vulvar cancer, vaginal cancer, penile cancer, and oropharyngeal cancer. Squamous cell carcinoma (SCC) in... (Review)
Review
Human papillomavirus (HPV) causes cervical cancer, anal cancer, vulvar cancer, vaginal cancer, penile cancer, and oropharyngeal cancer. Squamous cell carcinoma (SCC) in the genital region in particular is recognized to be caused by HPV infection, and intraepithelial lesions of the penis and vulva are termed penile intraepithelial neoplasia and vulvar intraepithelial neoplasia, respectively. Although SCC of the nail apparatus is recognized as being associated with high-risk HPVs, it is not well-known in general medicine, and its analysis has been insufficient. In this article, we reviewed 136 cases of HPV-associated nail SCC and SCC in situ and delineated their clinical characteristics. We found that half of the cases were high-risk HPV-associated. Almost all of the types were high-risk α-HPVs. This disease had a male dominance and left hand digit 3 and right hand digits 1-3 were typically affected. In this review, 24% of the cases of nail SCC had a history of other HPV-associated diseases, suggesting the possibility of genitodigital transmission. We propose that nail SCC is a hidden high-risk HPV-associated reservoir and should be recognized as a sexually transmitted infection.
Topics: Carcinoma, Squamous Cell; Disease Reservoirs; Female; Humans; Male; Nail Diseases; Papillomaviridae; Papillomavirus Infections; Risk Factors; Sexually Transmitted Diseases; Skin Neoplasms
PubMed: 30930083
DOI: 10.1016/j.jaad.2019.03.070 -
Microorganisms May 2022Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. Although most HPV infections will spontaneously resolve, a... (Review)
Review
Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. Although most HPV infections will spontaneously resolve, a considerable proportion of them will persist, increasing the risk of anogenital dysplasia, especially within certain populations, such as patients infected with human immunodeficiency virus (HIV). Furthermore, high-risk oncogenic HPV types (HR-HPV) are the main cause of cervix and other anogenital cancers, such as cancer of the vagina, vulva, penis, or anus. HIV and HPV coinfection is common among people living with HIV (PLWH) but disproportionally affects men who have sex with men (MSM) for whom the rate of persistent HPV infection and reinfection is noteworthy. The molecular interactions between HIV and HPV, as well as the interplay between both viruses and the immune system, are increasingly being understood. The immune dysfunction induced by HIV infection impairs the rate of HPV clearance and increases its oncogenic risk. Despite the availability of effective antiretroviral therapy (ART), the incidence of several HPV-related cancers is higher in PLWH, and the burden of persistent HPV-related disease has become a significant concern in an aging HIV population. Several public health strategies have been developed to reduce the transmission of HIV and HPV and mitigate the consequences of this type of coinfection. Universal HPV vaccination is the most effective preventive tool to reduce the incidence of HPV disease. In addition, screening programs for HPV-related cervical and vulvovaginal diseases in women are well-recognized strategies to prevent cervical cancer. Similarly, anal dysplasia screening programs are being implemented worldwide for the prevention of anal cancer among PLWH. Herein, the main epidemiological features and clinical implications of HIV and HPV coinfection are reviewed, focusing mainly on the relationship between HIV immune status and HPV-related diseases and the current strategies used to reduce the burden of HPV-related disease.
PubMed: 35630489
DOI: 10.3390/microorganisms10051047 -
Acta Obstetricia Et Gynecologica... Jan 2024Vulva squamous cell carcinoma (VSCC) develops through two separate molecular pathways-one involving high-risk human papilloma virus infection (HPV-associated), and the...
INTRODUCTION
Vulva squamous cell carcinoma (VSCC) develops through two separate molecular pathways-one involving high-risk human papilloma virus infection (HPV-associated), and the other without HPV infection (HPV-independent) often involving TP53 mutation. HPV-associated VSCC generally has a better progression-free survival than HPV-independent VSCC. The aim of this study was to determine TP53 mutation status using immunohistochemistry, compare different methods of HPV detection and correlate both with survival in a retrospective cohort of 123 patients with VSCC.
MATERIAL AND METHODS
Immunohistochemistry for p53, Ki67 and p16 (a surrogate marker for HPV infection) was performed on formalin-fixed paraffin-embedded tissues from a cohort of surgically treated VSCC patients to identify molecular subtypes of VSCC. Presence of HPV infection was detected by HPV DNA PCR and HPV mRNA in situ hybridization (ISH). The Pearson chi-square test and multivariable Cox regression model were used to investigate the association of different parameters with progression-free survival and disease-specific survival (DSS), and Kaplan-Meier curves were used to show the association of different parameters with survival.
RESULTS
The results of p53 and p16 immunohistochemistry confirmed three VSCC subtypes associated with different prognosis. The TP53 mutation status was identified as an independent prognostic factor of worse progression-free survival (p = 0.024) after adjustment for FIGO stage. p16 immunohistochemistry, mRNA ISH, and DNA PCR had excellent concordance in terms of HPV detection. According to the multivariable Cox regression model, the presence of hrHPV mRNA correlated significantly with increased progression-free survival (p = 0.040) and DSS (p = 0.045), after adjustment for other confounders.
CONCLUSIONS
p53 and p16 immunohistochemistry stratify VSCC cohort into three subtypes with TP53mutated patients having the worst prognosis. The detection of hrHPV mRNA by ISH was an independent predictor of increased survival. Thus, the combined detection of p53 and HPV mRNA might improve risk stratification in VSCC.
Topics: Female; Humans; Prognosis; Human Papillomavirus Viruses; Papillomavirus Infections; Retrospective Studies; Cyclin-Dependent Kinase Inhibitor p16; Tumor Suppressor Protein p53; Carcinoma, Squamous Cell; Vulvar Neoplasms; DNA; RNA, Messenger; Vulva; Papillomaviridae
PubMed: 37840151
DOI: 10.1111/aogs.14689