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Modern Pathology : An Official Journal... Oct 2022Vulvar squamous cell carcinomas and their precursors are currently classified by the World Health Organization based on their association with high-risk human... (Review)
Review
HPV-independent, p53-wild-type vulvar intraepithelial neoplasia: a review of nomenclature and the journey to characterize verruciform and acanthotic precursor lesions of the vulva.
Vulvar squamous cell carcinomas and their precursors are currently classified by the World Health Organization based on their association with high-risk human papillomavirus (HPV). HPV independent lesions often harbor driver alterations in TP53, usually seen in the setting of chronic vulvar inflammation. However, a group of pre-invasive vulvar squamous lesions is independent from both HPV and mutant TP53. The lesions described within this category feature marked acanthosis, verruciform growth and altered squamous maturation, and over the last two decades several studies have added to their characterization. They have a documented association with verrucous carcinoma and conventional squamous cell carcinoma of the vulva, suggesting a precursor role. They also harbor recurrent genomic alterations in several oncogenes, mainly PIK3CA and HRAS, indicating a neoplastic nature. In this review, we provide a historical perspective and a comprehensive description of these lesions. We also offer an appraisal of the terminology used over the years, going from Vulvar Acanthosis with Altered Differentiation and Verruciform Lichen Simplex Chronicus to Differentiated Exophytic Vulvar Intraepithelial Lesion and Vulvar Aberrant Maturation, the latter term having been recently proposed by the International Society for the Study of Vulvovaginal Diseases. In line with the recognition of these lesions by the 2020 World Health Organization Classification of Tumours as a neoplastic precursor, we herein propose the term HPV-independent, p53-wild-type verruciform acanthotic Vulvar Intraepithelial Neoplasia (HPVi(p53wt) vaVIN), which better conveys not only the pathology but also the neoplastic nature and the biologic risk inherent to these uncommon and challenging lesions. We outline strict morphologic and immunohistochemical criteria for its diagnosis and distinction from mimickers. Immunohistochemistry for p16 and p53 should be performed routinely in the diagnostic work-up of these lesions, and the morphologic alternative term vaVIN should be reserved for instances in which p16/HPV/p53 status is unknown. We also discuss management considerations and the need to further explore precursors within and beyond the spectrum of verruciform acanthotic vulvar intraepithelial neoplasia.
Topics: Biological Products; Carcinoma in Situ; Carcinoma, Squamous Cell; Class I Phosphatidylinositol 3-Kinases; Female; Humans; Papillomaviridae; Papillomavirus Infections; Precancerous Conditions; Squamous Intraepithelial Lesions; Tumor Suppressor Protein p53; Vulva; Vulvar Neoplasms
PubMed: 35437330
DOI: 10.1038/s41379-022-01079-7 -
International Journal of Gynecological... Feb 2020Lower extremity lymphedema is a chronic, often irreversible condition that affects many patients treated for gynecologic malignancies, with published rates as high as... (Review)
Review
Lower extremity lymphedema is a chronic, often irreversible condition that affects many patients treated for gynecologic malignancies, with published rates as high as 70% in select populations. It has consistently been shown to affect multiple quality of life metrics. This review focuses on the pathophysiology, incidence, trends, and risk factors associated with lower extremity lymphedema secondary to the treatment of cervical, endometrial, ovarian, and vulvar cancers in the era of sentinel lymph node mapping. We review traditional and contemporary approaches to diagnosis and staging, and discuss new technologies and imaging modalities. Finally, we review the data-based treatment of lower extremity lymphedema and discuss experimental treatments currently being developed. This review highlights the need for more prospective studies and objective metrics, so that we may better evaluate and serve these patients.
Topics: Female; Genital Neoplasms, Female; Humans; Leg; Lymphedema; Sentinel Lymph Node Biopsy
PubMed: 31915136
DOI: 10.1136/ijgc-2019-001032 -
International Journal of Gynaecology... Oct 2021Vulvar cancer is an uncommon gynecological malignancy primarily affecting postmenopausal women. There is no specific screening and the most effective strategy to reduce...
Vulvar cancer is an uncommon gynecological malignancy primarily affecting postmenopausal women. There is no specific screening and the most effective strategy to reduce vulvar cancer incidence is the opportune treatment of predisposing and preneoplastic lesions associated with its development. While vulvar cancer may be asymptomatic, most women present with vulvar pruritus or pain, or have noticed a lump or ulcer. Therefore, any suspicious vulvar lesion should be biopsied to exclude invasion. Once established, the most common subtype is squamous cell carcinoma. Treatment of vulvar cancer depends primarily on histology and surgical staging. Treatment is predominantly surgical, particularly for squamous cell carcinoma, although concurrent chemoradiation is an effective alternative, particularly for advanced tumors. Management should be individualized and carried out by a multidisciplinary team in a cancer center experienced in the treatment of these tumors.
Topics: Carcinoma, Squamous Cell; Chemoradiotherapy; Female; Humans; Neoplasm Staging; Vulva; Vulvar Neoplasms
PubMed: 34669204
DOI: 10.1002/ijgo.13881 -
Current Oncology (Toronto, Ont.) Aug 2021Extramammary Paget's disease (EMPD) is a rare neoplasm that usually develops in apocrine gland-bearing areas, such as the vulva, scrotum, and penis. EMPD may present... (Review)
Review
Extramammary Paget's disease (EMPD) is a rare neoplasm that usually develops in apocrine gland-bearing areas, such as the vulva, scrotum, and penis. EMPD may present with a focal, multifocal, or an ectopic lesion. Clinically, EMPD lesions often exhibit infiltrative erythema, which is sometimes similar to other skin disorders such as eczema. While primary EMPD arises as intraepithelial neoplasm of the epidermis, EMPD-like lesions may occur from epidermotropic spread of malignant cells or direct extension from an underlying internal neoplasm, known as secondary EMPD. Because treatment strategies differ for primary EMPD and secondary EMPD, accurate diagnosis based on detailed histopathological evaluation is required. In the early stages, EMPD usually shows indolent growth, and most cases are diagnosed as carcinoma in situ. However, invasive lesions may result in metastases, and deep invasion is associated with high incidence of metastases. Conventional chemotherapies have been used for EMPD treatment in patients with distant metastases, but the efficacy is not satisfactory, and the prognosis for such patients remains poor. Recent studies have provided various insights into the molecular pathogenesis of the development and advancement of EMPD, which may lead to novel treatment approaches for metastatic EMPD. This review addresses the diagnosis, pathogenesis, and treatment of EMPD with focus on recent progress in understanding this disease.
Topics: Female; Humans; Male; Paget Disease, Extramammary; Prognosis; Scrotum
PubMed: 34436026
DOI: 10.3390/curroncol28040260 -
Cancer Discovery Aug 2021Human papillomavirus (HPV) infection drives tumorigenesis in the majority of cervical, oropharyngeal, anal, and vulvar cancers. Genetic and epidemiologic evidence has... (Review)
Review
Human papillomavirus (HPV) infection drives tumorigenesis in the majority of cervical, oropharyngeal, anal, and vulvar cancers. Genetic and epidemiologic evidence has highlighted the role of immunosuppression in the oncogenesis of HPV-related malignancies. Here we review how HPV modulates the immune microenvironment and subsequent therapeutic implications. We describe the landscape of immunotherapies for these cancers with a focus on findings from early-phase studies exploring antigen-specific treatments, and discuss future directions. Although responses across these studies have been modest to date, a deeper understanding of HPV-related tumor biology and immunology may prove instrumental for the development of more efficacious immunotherapeutic approaches. SIGNIFICANCE: HPV modulates the microenvironment to create a protumorigenic state of immune suppression and evasion. Our understanding of these mechanisms has led to the development of immunomodulatory treatments that have shown early clinical promise in patients with HPV-related malignancies. This review summarizes our current understanding of the interactions of HPV and its microenvironment and provides insight into the progress and challenges of developing immunotherapies for HPV-related malignancies.
Topics: Female; Humans; Immunotherapy; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Uterine Cervical Neoplasms
PubMed: 33990345
DOI: 10.1158/2159-8290.CD-20-1760 -
Radiology and Oncology Sep 2020Background Vulvar cancer accounts for 3-5% of malignant diseases of the female genital tract. The Slovenian incidence rate is 5.5/100,000, which means 57 new cases per... (Review)
Review
Background Vulvar cancer accounts for 3-5% of malignant diseases of the female genital tract. The Slovenian incidence rate is 5.5/100,000, which means 57 new cases per year. The most common histological type (90%) is squamous cell carcinoma. Based on etiology, it can be classified into the first type which correlates with human papillomavirus (HPV) infection and the second type which is not associated with HPV. The most common and long-lasting symptom of vulvar cancer is pruritus. The preferred diagnostic procedure to confirm the diagnosis is a punch or incision biopsy. Surgery in combination with radiotherapy is the standard treatment for vulvar cancer. Sentinel lymph node biopsy with lymphoscintigraphy is now a standard part of surgical treatment. Chemotherapy is a palliative treatment option. Conclusions Vulvar cancer is a rare disease. Because of the pathogenesis, surgery and radiotherapy are the main treatment modalities. The sentinel node biopsy (SNB) represents a contemporary approach to the vulvar cancer treatment and significantly reduces morbidity. Improvements in treatment of vulvar cancer contributed to the decrease of mortality among Slovenian women.
Topics: Combined Modality Therapy; Female; Humans; Incidence; Lymphoscintigraphy; Sentinel Lymph Node Biopsy; Vulvar Neoplasms
PubMed: 32960779
DOI: 10.2478/raon-2020-0053 -
International Journal of Gynecological... Apr 2023The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of... (Review)
Review
The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) consensus statement on the management of vaginal...
The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.
Topics: Female; Pregnancy; Humans; Colposcopy; Papillomavirus Infections; Quality of Life; Vaginal Neoplasms; Imiquimod; Uterine Cervical Dysplasia; Carcinoma in Situ; Retrospective Studies; Uterine Cervical Neoplasms
PubMed: 36958755
DOI: 10.1136/ijgc-2022-004213 -
International Journal of Gynecological... Mar 2022Vaginal cancer is a rare cancer. A lot of the data used in the treatment of this cancer are extrapolated from cervical cancer data. Radiation therapy plays a significant... (Review)
Review
Vaginal cancer is a rare cancer. A lot of the data used in the treatment of this cancer are extrapolated from cervical cancer data. Radiation therapy plays a significant role in the treatment of vaginal cancer. The advances in radiation therapy in both external beam and brachytherapy have improved local control, survival, and toxicity. Brachytherapy plays an important role in treating vaginal cancer, but treatment should be individualized to each tumor. Imaging, particularly magnetic resonance imaging, plays an essential role in the management of patients with vaginal cancer, from diagnosis to staging to treatment management to surveillance.
Topics: Brachytherapy; Carcinoma in Situ; Female; Humans; Magnetic Resonance Imaging; Uterine Cervical Neoplasms; Vagina; Vaginal Neoplasms
PubMed: 35256422
DOI: 10.1136/ijgc-2021-002517 -
BMJ Open Dec 2021Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer.
METHODS
Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002-2005. HPV vaccine cohorts comprised originally 16-17 year-old HPV 16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2465) and HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866). Altogether, 3341 vaccines were followed by the Finnish Cancer Registry in the same way as 16 526 non-HPV-vaccinated controls. The control cohort stemmed from 15 665 originally 18-19 years-old women enrolled in 2003 (6499) or 2005 (9166) and 861 placebo recipients of the FUTURE II trial. The follow-up started 6 months after the clinical trials in 2007 and 2009 and ended in 2019. It was age aligned for the cohorts.
FINDINGS
During a follow-up time of up to 11 years, we identified 17 HPV-positive invasive cancer cases (14 cervical cancers, 1 vaginal cancer, 1 vulvar cancer and 1 tongue cancer) in the non-HPV-vaccinated cohorts and no cases in the HPV-vaccinated cohorts. HPV typing of diagnostic tumour blocks found HPV16 in nine cervical cancer cases, HPV18, HPV33 and HPV52 each in two cases and HPV45 in one cervical cancer case. The vaginal, vulvar and tongue cancer cases were, respectively, positive for HPV16, HPV52/66 and HPV213. Intention-to-treat vaccine efficacy against all HPV-positive cancers was 100% (95% CI 2 to 100, p<0.05).
INTERPRETATION
Vaccination is effective against invasive HPV-positive cancer.
TRIAL REGISTRATION NUMBER
NCT00122681, Post-results; NCT00169494, Post-results; NCT00092534, Post-results.
Topics: Adolescent; Adult; Female; Follow-Up Studies; Human papillomavirus 16; Human papillomavirus 18; Humans; Papillomavirus Infections; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Vaccine Efficacy; Young Adult; Uterine Cervical Dysplasia
PubMed: 35149535
DOI: 10.1136/bmjopen-2021-050669 -
American Journal of Clinical Dermatology Sep 2021Ten percent of all women have pigmented vulvar lesions. Fortunately, most of these are benign but 1% of all melanomas in women affect the vulva. While the mortality rate... (Review)
Review
Ten percent of all women have pigmented vulvar lesions. Fortunately, most of these are benign but 1% of all melanomas in women affect the vulva. While the mortality rate of cutaneous melanoma has dropped by 7% annually during the last 5 years, the prognosis of vulvar melanoma remains dismal: the 5-year overall survival rate is 47% compared with 92% for cutaneous melanoma. The current evidence suggests that this likely results from a combination of delayed diagnosis and different tumor biology, treatment strategies, and treatment response. Although many landmark trials on checkpoint inhibitors included mucosal and vulvar melanomas, the results were often not reported separately. Post-hoc analyses indicate overall response rates between 19 and 37% for checkpoint inhibitors. A recently published retrospective study on vulvar melanomas suggests an objective response in 33.3% with a similar safety profile to cutaneous melanoma. Tyrosine kinase inhibitors may be considered in recurrent disease if a c-KIT mutation is present.
Topics: Diagnosis, Differential; Female; Humans; Melanoma; Skin Neoplasms; Vulva; Vulvar Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 34125416
DOI: 10.1007/s40257-021-00614-7