Clinical and histologic features of vulvar carcinomas analyzed for human papillomavirus status: Evidence that squamous cell carcinoma of the vulva has more than one etiology

ArticleinHuman Pathlogy 22(7):711-8 · August 1991with5 Reads
DOI: 10.1016/0046-8177(91)90294-Y · Source: PubMed
Abstract
The association between the human papillomavirus (HPV) and malignant neoplasms of the uterine cervix is well established; however, its role in the pathogenesis of vulvar cancer has not been well defined. This study correlates the clinical and histopathologic features of 21 invasive carcinomas of the vulva with the presence of HPV DNA as detected by Southern blot and polymerase chain reaction (PCR) analysis. By one or both techniques, HPV DNA was detected in 10 of the 21 tumors analyzed; all HPVs containing tumors hybridized with HPV-16 probes, although PCR also detected HPV-6 in two of the HPV-16-containing tumors. No HPV-18 DNA was detected in any tumor by PCR or Southern blot hybridization. Both the invasive cancer and the surrounding intraepithelial disease tended to display histopathologic features that usually could distinguish HPV-associated cancers from those without HPV DNA. The intraepithelial lesions associated with HPV-containing tumors were of the bowenoid type with koilocytosis, while tumors lacking HPV generally demonstrated a simplex type of intraepithelial lesion. Invasive tumors with no viral DNA were more frequently keratinizing than the HPV-containing cancers. Race, parity, hormonal therapy, and alcohol use did not affect the HPV status; however, HPV DNA was more prevalent in the tumors of younger women and in those with a history of tobacco use. Human papillomavirus status had no impact on the stage of disease or its prognosis. These findings identify two subsets of vulvar carcinoma cases based on HPV hybridization data and the histopathologic characteristics of the tumor.
    • "While there is compelling evidence to suggest that in cancers of the vagina, anus, penis, and oropharynx , patients with HPV-positive tumours display better diseasespecific survival, the relationship between virus positivity and outcome is less clear in women with VSCC. Whereas some studies report a substantial survival advantage for HPV-positive patients, others report no difference [30][31][32][33][34]. In our cohort study, we found no evidence that HPV positivity confers a survival advantage. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: In this study, we investigated if the presence of histologically abnormal epithelium adjacent to the primary tumour influenced the frequency, timing, and topography of local vulvar recurrences (LVR) following treatment for squamous cell carcinoma of the vulva (VSCC). Methods: The study population comprised a cohort of 201 consecutive cases with incident VSCC. LVR were categorised as local relapses (LR) if they occurred <2cm from the tumour margins, and as second field tumours (SFT) when ≥2cm from these margins. Univariable and multivariable competing risk modelling was performed to identify the prognostic factors associated with local disease recurrence. Results: The characterization of the epithelium adjacent to the invasive component was possible for 199 (99.0%) patients. Of these, 171 (85.9%) were found to have intraepithelial abnormalities found adjacent to the surgical specimen. Multivariable analyses revealed that, following adjustment, Lichen Sclerosis (LS) was associated with an increase in the incidence of LVR, LR and SFT (SHRs: 3.4, 2.7 and 4.4, respectively). Although the incidence of LR and SFT in women with LS associated VSCC was similar, the peak incidence of SFT occurred more than two years before that of LR. Conclusions: Women with VSCC arising in a field of LS may continue to have an increased risk of developing LR and SFT for many years after resection of their primary tumour. Our study suggests that these women should be followed up more regularly so that LVR can be detected earlier; unless a more robust surveillance programme or chemopreventative treatments become available.
    Article · Jul 2016
    • "There are conflicting data about the role of HPV status as a prognostic factor in VSCC. An overview of studies on the presence of HPV and impact on prognosis is given in Table 3(Alonso et al., 2011; Lindell et al., 2010; Monk et al., 1995; Bloss et al., 1991; Ansink et al., 1994; Larsson et al., 2012; Pinto et al., 2004; Hording et al., 1993; van de Nieuwenhof et al., 2009). The presence of HPV DNA can be detected by PCR (sequencing or INNO-LiPA) or in situ hybridization. "
    [Show abstract] [Hide abstract] ABSTRACT: Recurrent disease occurs in 12-37% of patients with vulvar squamous cell carcinoma (VSCC). Decisions about treatment of recurrent VSCC mainly depend on the location of the recurrence and previous treatment, resulting in individualized and consensus-based approaches. Most recurrences (40–80%) occur within 2 years after initial treatment. Currently, wide local excision is the treatment of choice for local recurrences. Isolated local recurrence of VSCC has a good prognosis, with reported 5-year survival rates of up to 60%. Groin recurrences and distant recurrences are less common and have an extremely poor prognosis. For groin recurrences, surgery with or without (chemo) radiotherapy are treatment options, depending on prior treatment. For distant recurrences, there are only palliative treatment options. In this review, we give an overview of the available literature and discuss epidemiology, risk factors, and prognostic factors for the different types of recurrent VSCC and we describe treatment options and clinical outcome.
    Full-text · Article · Jul 2016
    • "Although evidence shows improved survival of HPV-induced and p16-positive carcinoma associated with head and neck cancer[50], no detailed studies are found presenting the survival data including both HPV status and p16 INK4a .A very few studies presented recurrence rate related to p16 concerning vulvar squamous cell carcinoma (VSCC) after repeated searches for several times, which may be due to the low frequency of VSCC. Among the included studies, HPV-positive rate independent of p16 INK4a ranges between 0% and 41% [23,25,27,34],which is in accordance with the fact that vulvar cancer presents an overall HPV infection rate of only 30%–40%[51][52].Moreover, the analysis outcome shows that p16 ink4a overexpression correlates significantly with the HPVpositive status, strongly supporting the etiological role of HPV infection in the development of vulvar cancer. The E7 and E6 oncoproteins encoded by HPV can be integrated into the host genome, binding to the tumor suppressor proteins pRB and p53, respectively, and leading to their deregulation, which results in the overexpression of p16 INK4A as a means of genetic instability control[53].All these may reasonably lead to the speculation that p16INK4a is only associated with HPV-induced vulvar carcinoma. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: This study aimed to examine the prognostic value of overexpressed p16INK4a in vulvar cancer. Although the tumor suppressor p16INK4a has been shown to be of prognostic value in a wide variety of cancers and precancerous lesions, its role in the vulvar cancer is still unclear. Methods: All publications in English language on the association between p16INK4a and clinicopathological features of vulvar cancer were searched from Pubmed, Embase, and Web of Science, and those in Chinese language were identified manually and online from the China National Knowledge Infrastructure. Strict inclusion and exclusion criteria were followed. Odds ratios(ORs) or risk ratios(RRs) with 95% confidence intervals(CIs) were pooled to assess the strength of association. Publication bias was estimated using funnel plots and the Egger's regression test. Results: A total of 17 studies with 2309 patients were included. The p16INK4a overexpression was found to correlate significantly with the lower International Federation of Gynecology and Obstetrics stage(I+II vs III+IV; OR = 0.60,95%CI:0.41-0.86,P = 0.006),negative lymph node metastasis(negative vs positive; OR = 0.61,95%CI:0.39-0.95,P = 0.029),patient's age<55(OR = 0.54,95%CI:0.31-0.96,P = 0.034),human papillomavirus-positive status(OR = 0.01,95%CI:0.00-0.11,P<0.001),and higher overall survival(RR = 0.53,95%CI = 0.35-0.80,P = 0.003). Conclusion: The p16INK4a might be associated with a higher survival and indicates better prognosis of vulvar cancer.
    Full-text · Article · Mar 2016
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