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Molecular Aspects of Medicine Dec 2023Human papillomavirus (HPV) infection represents a significant global health concern owing to its role in the etiology of conditions ranging from benign low-grade lesions... (Review)
Review
Human papillomavirus (HPV) infection represents a significant global health concern owing to its role in the etiology of conditions ranging from benign low-grade lesions to cancers of the cervix, head and neck, anus, vagina, vulva, and penis. Prophylactic vaccination programs, primarily targeting adolescent girls, have achieved dramatic reductions in rates of HPV infection and cervical cancer in recent years. However, there is a clear demand for a strategy to manage the needs of the many people who are already living with persistent HPV infection and/or HPV-associated conditions. Unlike prophylactic vaccines, which act to prevent HPV infection, therapeutic vaccination presents an opportunity to induce cellular immunity against established HPV infections and lesions and prevent progression to cancer. Several HPV vaccines are undergoing clinical development, using a range of platforms. Peptide- or protein-based vaccines, vector-based vaccines, whole-cell vaccines, and nucleic acid vaccines each offer relative merits and limitations for the delivery of HPV antigens and the subsequent generation of targeted immune responses. There has been particular interest in DNA-based vaccines, which elicit both cellular and humoral immune responses to provide long-lasting immunity. DNA vaccines offer several practical advantages over other vaccine platforms, including the potential for rapid and scalable manufacturing, targeting of many different antigens, and potential for repeat boosting. Furthermore, unlike vectored approaches, DNA vaccines are thermostable over extended time periods, which may enable shipping and storage. Several delivery strategies are available to address the main challenge of DNA vaccines, namely their relatively low transfection efficiency. We review the latest clinical data supporting the development of DNA vaccines and reflect on this exciting prospect in the management of HPV-related disease.
Topics: Male; Female; Adolescent; Humans; Papillomavirus Infections; Vaccines, DNA; Uterine Cervical Neoplasms; Papillomavirus Vaccines; Human Papillomavirus Viruses
PubMed: 37931422
DOI: 10.1016/j.mam.2023.101224 -
Modern Pathology : An Official Journal... Jun 2023There is emerging evidence that vulvar squamous cell carcinoma (VSCC) can be prognostically subclassified into 3 groups based on human papillomavirus (HPV) and p53...
There is emerging evidence that vulvar squamous cell carcinoma (VSCC) can be prognostically subclassified into 3 groups based on human papillomavirus (HPV) and p53 status: HPV-associated (HPV+), HPV-independent/p53 wild-type (HPV-/p53wt), or HPV-independent/p53 abnormal (HPV-/p53abn). Our goal was to assess the feasibility of separating VSCC and its precursors into these 3 groups using p16 and p53 immunohistochemistry (IHC). A tissue microarray containing 225 VSCC, 43 usual vulvar intraepithelial neoplasia (uVIN/HSIL), 10 verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN), and 34 differentiated VIN (dVIN), was stained for p16 and p53. Noncomplementary p16 and p53 patterns were resolved by repeating p53 IHC and HPV RNA in situ hybridization (ISH) on whole sections, and sequencing for TP53. Of 82 p16-positive VSCC, 73 (89%) had complementary p16 and p53 patterns and were classified into the HPV+ group, 4 (4.9%) had wild-type p53 staining, positive HPV ISH and were classified into the HPV+ group, whereas 5 (6.1%) had p53 abnormal IHC patterns (1 null, 4 overexpression), negativity for HPV ISH, and harbored TP53 mutations (1 splice site, 4 missense); they were classified as HPV-/p53abn. Of 143 p16-negative VSCC, 142 (99.3%) had complementary p53 and p16 patterns: 115 (80.4%) HPV-/p53abn and 27 (18.9%) HPV-/p53wt. One had a basal-sparing p53 pattern, positivity for HPV ISH and was negative for TP53 mutations-HPV+ category. The use of IHC also led to revised diagnoses-HSIL to dVIN (3/43), dVIN to vaVIN (8/34), and dVIN to HSIL (3/34). Overall, 215/225 VSCC (95.6%) could be easily classifiable into 3 groups with p16 and p53 IHC. We identified several caveats, with the major caveat being that "double-positive" p16/p53 should be classified as HPV-/p53abn. We propose an algorithm that will facilitate the application of p16 and p53 IHC to classify VSCC in pathology practice.
Topics: Female; Humans; Papillomavirus Infections; Immunohistochemistry; Tumor Suppressor Protein p53; Vulvar Neoplasms; Carcinoma in Situ; Human Papillomavirus Viruses; Papillomaviridae; Carcinoma, Squamous Cell; Squamous Intraepithelial Lesions; Cyclin-Dependent Kinase Inhibitor p16
PubMed: 36828360
DOI: 10.1016/j.modpat.2023.100145 -
The Journal of Dermatology Mar 2023More than 200 types of human papillomavirus (HPV) have been reported to date and have been associated with various dermatological diseases. Among dermatological... (Review)
Review
More than 200 types of human papillomavirus (HPV) have been reported to date and have been associated with various dermatological diseases. Among dermatological diseases, viral verrucae are the most commonly reported to be associated with HPV. Epidermodysplasia verruciformis (EV) consists of three types: typical EV is an autosomal recessive genetic disorder with TMC6/TMC8 gene mutations, atypical EV develops due to various gene mutations that cause immunodeficiency, and acquired EV develops due to acquired immunodeficiency. Generalized verrucosis differs from EV in that it involves numerous verrucous nodules (mainly on the limbs), histopathologically no blue cells as seen in EV, and infection with cutaneous α-HPVs as well as β-HPVs. HPV-induced skin malignancies include squamous cell carcinoma (SCC) caused by β-HPV (especially HPV types 5 and 8) in EV patients, organ transplant recipients, and healthy individuals, and SCC of the vulva and nail unit caused by mucosal high-risk HPV infection. Carcinogenesis of β-HPV is associated with sunlight. Mucosal high-risk HPV-associated carcinomas may also be sexually transmitted. We focused on Bowen's disease of the nail, which has been the subject of our research for a long time and has recently come to the fore in the field of dermatology.
Topics: Female; Humans; Papillomavirus Infections; Skin; Skin Neoplasms; Carcinoma, Squamous Cell; Epidermodysplasia Verruciformis; Human Papillomavirus Viruses; Papillomaviridae; Membrane Proteins
PubMed: 36601717
DOI: 10.1111/1346-8138.16697 -
BJOG : An International Journal of... May 2020No consensus on the management of symptomatic cysts or abscesses of the Bartholin's gland exists.
BACKGROUND
No consensus on the management of symptomatic cysts or abscesses of the Bartholin's gland exists.
OBJECTIVES
To assess the effectiveness and safety of surgical interventions for a symptomatic Bartholin's cyst or abscess.
SEARCH STRATEGY
We searched bibliographical databases from inception to April 2019.
SELECTION CRITERIA
Randomised trials evaluating a surgical intervention for the treatment of a symptomatic Bartholin's cyst or abscess.
DATA COLLECTION AND ANALYSIS
Eight trials, reporting data from 699 women, were included. Study characteristics and methodological quality were recorded for each trial. Summary estimates were calculated using random-effects methods.
MAIN RESULTS
When considering the recurrence of a symptomatic Bartholin's cyst or abscess, the evidence was consistent with notable effects in either direction (risk ratio [RR] 0.76; 95% confidence interval [CI] 0.41-1.40) when comparing marsupialisation with incision, drainage and insertion of a Word catheter. Limited inference could be made when comparing marsupialisation with incision, drainage and silver nitrate insertion (RR 1.00; 95% CI 0.57-1.75), and incision, drainage and cavity closure (RR 0.25; 95% CI 0.01-4.89). There was limited reporting of secondary outcomes, including haematoma, infectious morbidity and persistent dyspareunia.
CONCLUSIONS
Current randomised trial evidence does not support the use of any single surgical intervention for the treatment of a symptomatic cyst or abscess of the Bartholin's gland.
PROSPECTIVE REGISTRATION
PROSPERO: International Prospective Register of Systematic Reviews; CRD42018088553.
TWEETABLE ABSTRACT
Further research is needed to identify an effective treatment for #Bartholin's cyst or abscess. @jamesmnduffy.
Topics: Ablation Techniques; Abscess; Bartholin's Glands; Cysts; Drainage; Female; Gynecologic Surgical Procedures; Humans; Needs Assessment; Randomized Controlled Trials as Topic; Vulvar Diseases
PubMed: 31876985
DOI: 10.1111/1471-0528.16079 -
Annals of Oncology : Official Journal... Feb 2020Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical... (Meta-Analysis)
Meta-Analysis
Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature.
BACKGROUND
Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other human papillomavirus (HPV)- and non-HPV-related malignancies after CIN treatment and infer its magnitude compared with the general population.
MATERIALS AND METHODS
Design: Systematic review and meta-analysis. Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment.
DATA SYNTHESIS
Summary effects were estimated using random-effects models.
OUTCOMES
Incidence rate of cervical cancer among women treated for CIN (per 100 000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated for CIN versus the general population.
RESULTS
Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100 000 woman-years (95% confidence interval 22-69). The RR of cervical cancer was elevated compared with the general population (3.30, 2.57-4.24; P < 0.001). The RR was higher for women more than 50 years old and remained elevated for at least 20 years after treatment. The RR of vaginal (10.84, 5.58-21.10; P < 0.001), vulvar (3.34, 2.39-4.67; P < 0.001), and anal cancer (5.11, 2.73-9.55; P < 0.001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5.04, 0.69-36.94; P = 0.073).
CONCLUSIONS
Women treated for CIN have a considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared with the general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women more than 50 years of age. Prolonged follow-up beyond the last screening round may be warranted for previously treated women.
Topics: Alphapapillomavirus; Female; Humans; Incidence; Middle Aged; Papillomavirus Infections; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 31959338
DOI: 10.1016/j.annonc.2019.11.004 -
Sub-cellular Biochemistry 2023Human papillomavirus (HPV) is associated with infection of different tissues, such as the cervix, anus, vagina, penis, vulva, oropharynx, throat, tonsils, back of the...
Human papillomavirus (HPV) is associated with infection of different tissues, such as the cervix, anus, vagina, penis, vulva, oropharynx, throat, tonsils, back of the tongue, skin, the lungs, among other tissues. HPV infection may or may not be associated with the development of cancer, where HPVs not related to cancer are defined as low-risk HPVs and are associated with papillomatosis disease. In contrast, high-risk HPVs (HR-HPVs) are associated with developing cancers in areas that HR-HPV infects, such as the cervix. In general, infection of HPV target cells is regulated by specific molecules and receptors that induce various conformational changes of HPV capsid proteins, allowing activation of HPV endocytosis mechanisms and the arrival of the HPV genome to the human cell nucleus. After the transcription of the HPV genome, the HPV genome duplicates exponentially to lodge in a new HPV capsid, inducing the process of exocytosis of HPV virions and thus releasing a new HPV viral particle with a high potential of infection. This infection process allows the HPV viral life cycle to conclude and enables the growth of HPV virions. Understanding the entire infection process has been a topic that researchers have studied and developed for decades; however, there are many things to still understand about HPV infection. A thorough understanding of these HPV infection processes will allow new potential treatments for HPV-associated cancer and papillomatosis. This chapter focuses on HPV infection, the process that will enable HPV to complete its HPV life cycle, emphasizing the critical role of different molecules in allowing this infection and its completion during the HPV viral life cycle.
Topics: Male; Female; Humans; Papillomavirus Infections; Human Papillomavirus Viruses; Capsid Proteins; Papilloma; Skin
PubMed: 38159229
DOI: 10.1007/978-3-031-40086-5_8 -
Ugeskrift For Laeger Feb 2023Anal cancer risk is increased in certain risk groups including people living with HIV (PLWH), especially in men who have sex with men, but also in organ transplant... (Review)
Review
Anal cancer risk is increased in certain risk groups including people living with HIV (PLWH), especially in men who have sex with men, but also in organ transplant recipients and women with a history of cervical or vulva dysplasia or cancer. High-resolution anoscopy (HRA) is a tool to diagnose anal high-grade squamous intraepithelial lesions (HSIL), and HRA-guided treatment of anal HSIL has been shown to reduce the risk of anal cancer in PLWH. The purpose of this review is to increase the awareness of HRA but also of tertiary prevention by digital anal rectal examination.
Topics: Male; Humans; Female; Homosexuality, Male; Sexual and Gender Minorities; Risk Factors; Endoscopy; Anus Neoplasms; Anal Canal; HIV Infections; Papillomavirus Infections
PubMed: 36896618
DOI: No ID Found -
Australian Prescriber Dec 2020Vulvovaginitis is a commonly encountered problem in general practice. It usually presents with irritation and vaginal discharge A thorough examination is essential in... (Review)
Review
Vulvovaginitis is a commonly encountered problem in general practice. It usually presents with irritation and vaginal discharge A thorough examination is essential in order not to miss the less common causes. Investigations may be needed to confirm the diagnosis Candidiasis and bacterial vaginosis are the most common causes. Antifungals and antibiotics are therefore used in management Not all causes are infective. Several skin disorders can affect the vulva Ongoing or recurrent symptoms require careful evaluation and further investigation
PubMed: 33363301
DOI: 10.18773/austprescr.2020.055 -
Annales de Pathologie Jan 2022Vulvar squamous cell carcinoma arises from precursor lesions: vulvar intraepithelial neoplasias (VIN). Most of them are caused by the human papillomavirus (HPV), and the...
Vulvar squamous cell carcinoma arises from precursor lesions: vulvar intraepithelial neoplasias (VIN). Most of them are caused by the human papillomavirus (HPV), and the precursor lesion for this group is VIN usual type/high grade squamous intraepithelial lesion (uVIN/HSIL) of variable clinical presentation and having a light invasive potential. Some VIN are HPV-independent and arise in older women against the background of chronic dermatoses, mostly lichen sclerosus. Their histological diagnosis is more subtle. They have a higher invasive potential. A third precursor, leading to well-differentiated, or even verrucous, carcinomas, is still ill-defined to this day. We detail these lesions' clinics, histology, and biomarkers (immunohistochemical and molecular).
Topics: Aged; Carcinoma in Situ; Female; Humans; Papillomaviridae; Papillomavirus Infections; Squamous Intraepithelial Lesions; Vulvar Neoplasms
PubMed: 33744030
DOI: 10.1016/j.annpat.2021.02.014 -
Virus Research Sep 2020Although it has been established that persistent infection with high risk human papillomavirus (HR-HPV) is the main cause in the development of cervical cancer, the... (Review)
Review
Although it has been established that persistent infection with high risk human papillomavirus (HR-HPV) is the main cause in the development of cervical cancer, the HR-HPV infection is also related with the cause of a significant fraction of other human malignancies from the mucosal squamous epithelial such as anus, vagina, vulva, penis and oropharynx. HR-HPV infection induces cell proliferation, cell death evasion and genomic instability resulting in cell transformation, due to HPV proteins, which target and modify the function of differents cell molecules and organelles, such as mitochondria. Mitochondria are essential in the production of the cellular energy by oxidative phosphorylation (OXPHOS), in the metabolism of nucleotides, aminoacids (aa), and fatty acids, even in the regulation of cell death processes such as apoptosis or mitophagy. Thus, mitochondria have a significant role in the HPV-related cancer development. This review focuses on the role of HPV and mitochondria in HPV-related cancer development, and treatments associated to mitochondrial apoptosis.
Topics: Alphapapillomavirus; Apoptosis; DNA Damage; Female; Humans; Male; Mitochondria; Neoplasms; Oxidative Stress; Papillomavirus Infections; Reactive Oxygen Species; Viral Proteins
PubMed: 32445871
DOI: 10.1016/j.virusres.2020.198016