Epidemiological data

Vulvar cancer is the 4th most common type of gynecological cancer after cervical, endometrial and ovarian cancers. It is a rare entity that comprises approximately 6% of all malignant tumors of the female genital tract. The likelihood of developing vulvar carcinoma tends to with age [1]. Notably, there has been an upward trend in vulvar cancer incidence in recent decades, particularly among younger women. Persistent genital HPV (Human Papillomavirus) infection has been identified as a primary factor contributing to the development of vulvar neoplasia in this demographic [2]. In HIV-positive women, the presence of HIV-induced immunodeficiency plays a significant role in promoting HPV infection and its persistence. Consequently, this immunodeficiency makes these women more susceptible to developing genital cancers, including vulvar cancer [9]. Indeed, HIV-infected women control HPV infection much less well than uninfected women [10] and, among HIV-infected women, those with a CD4 + T-lymphocyte count of less than 200 cells. /mm3 are less likely to clear an HPV infection than women with a CD4 + T-lymphocyte count of between 200 and 500 cells/mm3 [9].

Our study revealed an annual frequency of 1.8 cases of vulvar cancer, reflecting its relatively low frequency. In Burkina Faso, Nayi Zongo et al. in 2016, reported an annual frequency of 8.4 cases of vulvar cancer [17]. The relatively low frequency in our series may be attributed to potential underestimation of cases, as some samples might not have reached the laboratory A study conducted by Amegbor K. et al. in Togo in 2011 found an annual frequency of 0.8 cases of vulvar cancer [18], which highlights the increasing prevalence of this cancer in our context.

The average age of the patients in our study was 48 ± 14.12 years with extremes of 27 years and 82 years. Historically, vulvar cancer is a relatively rare cancer, occurring most often in older women [19, 20]. However, over time, over time, there has been a noticeable shift with an increasing occurrence of vulvar cancer among younger women [7, 9, 11]. Several risk factors, such as persistent HPV infection, have been implicated in this changing trend [14, 15, 21].

Pathological data

The majority of vulvar cancers are histologically classified as squamous cell carcinomas, with melanoma, adenocarcinoma of the Bartholin glands, or skin tumors being less common occurrences [14, 15]. These cancers often presents macroscopically budding, ulcerated lesions and rarely nodular [1, 19].

The ulcero-budding aspect was the most recorded aspect with 31.3%, followed by the ulcerated aspect with 25%. This aligns with findings from Nayi Zongo’s study, where the ulcero-budding aspect was also the most predominant, reported in 81% of cases [17]. Existing literature also supports the ulcero-budding aspect as the most common presentation of vulvar cancer [9, 11]. Squamous cell carcinoma was the predominant histological type with 68.8%. Squamous cell carcinoma consistently ranks as the most frequent histological type of vulvar cancer in the literature [5, 7, 9,10,11]. Squamous cell cancers, much like cervical and vaginal cancers, is preceded by lesions of the intraepithelial neoplasia type VIN ( vulvar intraepithelial neoplasia), The transformation of these lesions into invasive cancer occurs at a rate of approximately 5 to 10%, whether bowenoid papulosis, genital warts or Bowen’s disease [9, 11]. Among the risk factors associated with vulvar cancer in our context, only HPV infection demonstrated a statistically significant association with the histological type of vulvar cancers (p-value = 0.0041). Similar findings were reported by studies conducted by M. Van Beurden in the Netherlands and Henri Azaïs in France, both of which identified the involvement of HPV in the development of vulvar cancer [22, 23].

Recent research focused on vulvar skin epithelium has shown that there are changes in the expression of the P53 protein that may precede the appearance of vulvar intraepithelial carcinomas. This suggests that P53 mutations could be an initial event in the genesis of vulvar carcinoma [24]. Dynes McConell reported that mutations in the P53 protein are found in more than 50% of vulvar cancers, and that genital HPV infection increases the risk of the occurrence of P53 mutations [24].

Therapeutic and prognostic data

Radiotherapy was delivered to 5 (15.63%) patients at a dose ranging from 60 to 70 Gy. Eight patients (25%) received chemotherapy based on cisplatin and 5-fluorouracil (5-FU).

The standard treatment for even small invasive carcinoma of the vulva was radical vulvectomy, which entails removing the primary tumor with a wide margin, followed by en-bloc resection of the inguinal lymph nodes and, in many cases,, pelvic lymph nodes [2]. This operation is said to have a high morbidity rate, with around 50% wound infections and post-operative complications [2]. For patients who are candidates for chemotherapy, chemoradiotherapy may be preferred, according to data in vulvar cancer [25]. Chemoradiotherapy is particularly recommended in cases involving anorectal, urethral, or bladder involvement, tumors attached to the bone, or lymph node involvement. The recommended chemotherapy agents include cisplatin, 5-FU, or mitomycin C, which are used in combination with radiation therapy. In some cases, surgery may be considered after chemotherapy and radiotherapy due to the reduction in tumor size achieved by this combination [26]. It’s worth noting that chemotherapy for vulvar cancer is often palliative and can be less effective due to the limited number of cases requiring this treatment. Therefore, there is currently no established standard treatment for such cases. Given the low response rate to conventional chemotherapies, there is increasing interest in exploring new biological agents like gefitinib and erlotinib. These agents, classified as reversible tyrosine kinase inhibitors, administered orally [27]. These enzymes are associated with the human epidermal growth factor receptor (EGFR), by inhibiting tyrosine kinase, gefitinib and erlotinib prevent EGFRs from stimulating uncontrolled cell growth that contributes to tumor growth. Gefitinib combined with trastuzumab has been studied in a human vulvar carcinoma cell line (A431) and appears to increase radiosensitivity [27].

Although the available data are fewer, patients who cannot undergo surgical treatment should receive primary radiotherapy [28]. The total radiation dose should be between 60 and 70 Gy, and the inguinal and pelvic regions should be treated bilaterally in case of positive lymph node involvement. Also, primary radiation therapy can be used preoperatively for women with advanced vulvar cancer. High rates of tumor shrinkage and complete responses at the time of surgery have been reported [28]. After 3 years of follow-up; survival was estimated at 78.13% in our patients.

The prognosis for patients with vulvar cancer is quite good when the treatment is given in time. Inguinal and/or femoral lymph node involvement is the most important prognostic factor for the survival of patients with vulvar cancer [29, 30]. Extracapsular growth of lymph node metastases, involvement of at least two lymph nodes and replacement of more than 50% of lymph nodes by tumor are predictive factors of poor survival [29, 31].

A immunohistochemical, p16 expression and HPV positivity are linked to a better prognosis, while p53 overexpression is linked to a worse prognosis; thus, biomarkers could help tailoring conventional treatment and follow-up [32]. The implications of PD-L1 positivity in reference to HPV status and prognosis are still not clear, even though pembrolizumab is part of available systemic therapies [32]. The role of tumor angiogenesis emerges through data on microvessel density, immunohistochemical VEGF staining and evaluation of serum VEGF concentrations. Few data exist on hormonal receptor expression, even though hormonal therapy showed great manageability [33].

The overall 5-year survival rate varies from 70 to 93% for patients whose nodes are negative and from 25 to 41% for those whose nodes are positive [31]. Other prognostic factors include stage, capillary lymphatic space invasion, and older age [31].

In most Western countries, the prognosis of patients with vulvar cancer has remained unchanged over the past two to four decades or has increased to a clinically insignificant extent [9]. Although infrequent, data showing a decrease in survival over time have also been published [9]. This disappointing situation is the result of multiple factors common to “orphan” diseases, including the difficulty of recruiting patients for treatment trials, the industry’s lack of interest in developing new effective therapies for small markets, the unavailability of specific screening techniques, the inability of health systems to promote the clinical detection of vulavirus cancers at an earlier stage and the absence of effective networks between primary/secondary health establishments and specialized tertiary centers [9] .

Limitations

Our study shares common limitations with other retrospective studies. Our study considered only biopsies that were received and processed at the pathological anatomy and cytology laboratory of the CHU Sylvanus Olympio, a functioning healthcare facility in the country. However, it’s important to acknowledge that this laboratory occasionally faces challenges in managing and processing all samples, particularly those originating from more remote regions within the country.



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