Carcinoma de células escamosas oral microinvasivo precedido por eritroplasia en un adulto joven

Oral squamous cell carcinoma positive for p16/human papilloma virus in post allogeneic stem cell transplantation: 2 cases and review of the literature

Background: The prevalence of high-risk Human Papillomaviruses (HPV) in cases of oral cavity squamous cell carcinoma (OSCC) varies widely. Therefore, the aim of this study was to determine the pooled prevalence of all high-risk HPV by meta-analysis with specific emphasis on HPV type 16/18. Methods: The studies were retrieved from PubMed and MEDLINE to conduct a comprehensive literature review on HPV detection in OSCC. Search terms included, High-risk HPV, oral cancer, polymerase chain reaction (PCR), in situ hybridization (ISH). We reviewed 47 research studies systematically to report the prevalence of high-risk HPV infection in oral cancer. Included studies published from 1988 to 2018. The meta-analysis was carried out by using MedCalc software version 19.0.3. Results: A meta-analysis was executed to calculate the pooled prevalence of High-risk HPV types, which revealed overall decreasing order frequency of high-risk HPV and high-risk type displaying the highest number of type16/18 HPV in the reported cases. As 30.71% [24.59 to 37.19 % confidence interval (CI) at 95%] and 28.88 % [22.62 to 35.57% confidence interval (CI) at 95%] followed by other high-risk HPV 3.59% [2.22 to 5.46%] respectively. Conclusions: According to present meta-analysis, we conclude that 16/18 HPV displaying maximum infection rate as compared to other high-risk HPV type in OSCC cases.

ObjectivesThe presence of and the causative role of high‐risk human papilloma virus (HPV) is a subject of controversy in oral squamous cell carcinoma (OSCC). The disagreement can be related to the misclassification of OSCC as oropharyngeal squamous cell carcinoma and/or lack of standard detection methods. This study aimed to examine the presence of transcriptionally active high‐risk HPV in a homogenous Norwegian cohort of primary and second primary OSCC of the mobile tongue (oral tongue squamous cell carcinoma—OTSCC).MethodsTissue microarrays containing formalin‐fixed and paraffin‐embedded cores of 146 OTSCC from the anterior 2/3 of the tongue (n = 128 primary and n = 18 second primary) from a multicentric Norwegian cohort were examined for the presence of high‐risk HPV by DNA‐ and RNA‐in situ hybridization (ISH) assays and p16 immunohistochemistry.ResultsTranscriptionally active HPV (E6/E7 mRNA) was not identified in any of the OTSCC specimens. In parallel, no tumors were positive for HPV by DNA ISH. Although, 61 (42%) OTSCC demonstrated p16 positivity with varying staining intensity and subcellular localization, only two cases demonstrated strong and uniform p16‐staining (both cytoplasmic and nuclear) in >70% of cancer cells. The absence of transcriptionally active high‐risk HPV in this cohort of OTSCC indicates that high‐risk HPV is an unlikely causative factor in the present material.

Human Papillomavirus has been associated with oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC), involving several risk factors in different parts of the world. This study aimed to determine the prevalence of high-risk HPV 16 and HPV 18, and factors associated with this prevalence, among patients with oral and oropharyngeal squamous cell carcinoma who attended Mulago Hospital, Uganda, from 2010 to 2015. This was a retrospective study in which 174 tissue blocks from individual patients, with confirmed oral and oropharyngeal squamous cell carcinoma, were retrieved from the archives. The corresponding medical charts of the patients were reviewed for demographic and clinical data. HE stained sections of the tissue blocks were reviewed for reconfirmation of OSCC& OPSCC. The samples were genotyped for HPV 16, 18 using Multiplex PCR techniques. The data was analysed using R. All 174 samples were confirmed positive for OSCC & OPSCC. HPV DNA was positive in 128 individuals (74%), 46 tested negative. HPV 16 alone occurred in 55 (32%) subjects and HPV 18 alone occurred in 37 (21%). Double infection was present in 36 individuals (21%). HIV was the only risk factor significantly associated with HPV 16 on OSCC& OPSCC (p = 0.018). Overall, HPV 16 and 18 are key etiological factors in oral and oropharyngeal squamous cell carcinoma pathogenesis in the Ugandan population, with a high prevalence. The results suggest that HIV positive individuals are at a higher risk of acquiring HPV 16 associated OPSCC. Alcohol consumption and cigarette smoking are not factors associated with HPV associated OPSCC in this study population.

Human papillomaviruses (HPV) may play an important role as one of the possible etiologies of oral squamous cell carcinoma (OSCC). The present study aimed to investigate the association between HPV and OSCC in young Japanese patients by examining the presence of HPV DNA and surrogate markers in OSCC tissues. Forty young patients with OSCC whose surgical specimens were available were analyzed and compared with 40 patients randomly recruited from a pool of patients aged >40 years. HPV DNA was detected using the polymerase chain reaction-based AMPLICOR(®) HPV test, and surrogate markers of HPV infection were analyzed using immunohistochemical techniques to detect p16(INK4a) and p53. Only two (5%) young patients and one (2.5%) older patient were positive for HPV DNA. p16(INK4a) overexpression was identified in six (15%) young patients. p53 staining levels were not high in tissues of most young patients (27 patients, 67.5%). HPV DNA status did not significantly correlate with p16(INK4a) expression levels. Profiles of increased levels of p16(INK4a) expression with diminished levels of p53 staining were not associated with the presence of HPV DNA. The combined p53 with p16(INK4a) profiles were significantly correlated with alcohol consumption in younger patients (p=0.006). RESULTS of the present study indicate that HPV is less likely to cause OSCC in young Japanese patients, and the p16(INK4a) expression level is not an appropriate surrogate marker for HPV infection in OSCC.

The purpose of this study was to evaluate the role of HPV and p53 polymorphisms in oral squamous cell carcinomas (OSCC) affecting Malaysian population. We analysed frozen samples from 105 OSCC as well as 105 oral specimens derived from healthy individuals. PCR assays targeting two regions of the virus were used. PCR amplification for the analysis of p53 codon 72 arginine/proline alleles was carried out in a separate reaction. HPV DNA was detected in 51.4% OSCC samples, while 24.8% controls were found to be HPV positive. HPV was found to be significantly associated with OSCC (P<0.001, OR=4.3 after adjustment for habits) when compared to controls. High-risk HPV was found to be significantly associated with OSCC cases (P<0.05). Demographic profiles of age, gender, race and habits were not associated with HPV presence in cases and controls. However, significantly less HPV positivity was seen in poorly differentiated compared to well-differentiated OSCCs. No significant association was found between HPV positivity and p53 polymorphisms in cases and control groups. Additionally, we found no association of codon 72 polymorphism with oral cancer. This study indicates that high-risk HPV infection is one of the contributing factors for OSCCs. HPV 16 was the predominant type found in Malaysian patients with OSCC. Further, we did not find any association between p53 codon 72 polymorphism and HPV infection or between the p53 polymorphism and the risk of oral cancer.

Simple SummaryThe incidence of oropharyngeal squamous cell carcinomas (OPSCCs) has increased in the last decades, and this seems to be correlated to the infectious epidemiological trend of human papillomavirus (HPV). The prevalence of HPV-positive OPSCCs is approximately 70%, with involvement mainly of the tonsillar area. On the role of HPV in oral squamous cell carcinoma (OSCC), very few studies have investigated the prevalence of HPV in strictly site-codified OSCC, excluding the base of the tongue as distinct oropharyngeal entity. As a result, an inappropriate estimation of HPV infection in OSCC has been observed. We investigated HPV status, using a combination of detection methods, in a sample of 40 subjects with OSCC coded by the latest site classifications. Moreover, we performed a critical review of the studies with the same outcomes. The main finding of our investigation was a low frequency of HPV-positive OSCC, suggesting no significant HPV role in strictly oral carcinogenesis.The aim of this study was to evaluate HPV status in oral squamous cell carcinoma (OSCC), as coded by the latest classifications and applying a combination of detection methods used in clinical practice. Forty-two patients with suspect OSCC were consecutively recruited. Patients underwent an incisional biopsy for histological OSCC diagnosis and HPV identification by PCR DNA and p16 IHC. All lesions were coded by the latest ICD-0-3.2 site/histology classifications, as proposed for OSCC by the National Cancer Institute Surveillance, Epidemiology and End Results Programs. Moreover, a comparative analysis review, critically evaluated by the same site-coded systems and HPV detection methods, was performed. In 40 confirmed cases of OSCC, the frequency of HPV infection was 10% (4/40). Among positive patients, two cases were PCR DNA/p16 IHC positive (high-risk HPV 51, high-risk HPV 67), two cases were PCR DNA positive/p16 IHC negative (high-risk HPV 31 + 68, high-risk HPV 66). Applying the latest site coding systems for OSCC, the frequency of HPV infection in this study and in similar, reviewed investigations was low (from 3.3% to 12.5%). These results suggested no significant HPV role in oral carcinogenesis, particularly where an updated site-coded classification of OSCCs (categorically excluding the base of the tongue) had been performed.

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Human papillomavirus expression in oral mucosa, premalignant conditions, and squamous cell carcinoma: A retrospective review of the literature

Distinct expression profiles of hsa-miR-31, hsa-miR-29c, hsa-miR-17, and hsa-miR-10a in oral epithelial dysplasia and squamous cell carcinoma.

Background. The major risk factors for oral squamous cell carcinoma (OSCC) are cigarette smoking, alcohol consumption, and betel quid chewing. In addition, human papillomavirus (HPV) infection has been associated with some OSCC. However, the relationships of HPVs to OSCCs remain unclear because of the difficulties in interpreting studies that demonstrate various prevalence rates of HPVs. We examined the prevalence of HPV in OSCCs. For HPV detection and genotyping, a sensitive and specific PCR-based method, the Roche Linear Array HPV genotyping kit test was used for these studies. Materials and Methods. Forty-five Japanese patients with OSCC were included in the present study. Surgical resection of primary tumors and normal tissues from all patients was performed at the Hospital of Tokyo Dental College, between December 2007 and December 2010. We assessed HPV infection in OSCC patients using the Roche Liner Array HPV genotyping Test, which can detect 37 different HPV types. Results. HPV was detected in 9 OSCC patients (20%). HPV subtype 39, 42 was the most prevalent type, but other types detected included 31, 33, 45 . . . high-risk types and 3, 6, 8 . . . low-risk types. Conclusion. The Roche Liner Array HPV genotyping Test is currently used as a standardized diagnostic test for HPV detection in cervical carcinoma in Europe. Some studies have shown that the most prevalent HPV subtype was the high-risk type HPV-16, However we showed that HPV is detected multiple type involved low- and high-risk type in oral carcinoma. We suggested that multiple subtypes of HPV implicated OSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 281. doi:10.1158/1538-7445.AM2011-281

This work demonstrates that a comprehensive strategy of proteomics identification combined with further validation and detailed functional analysis should be adopted in the field of cancer biomarker discovery. A comparative proteomics approach was utilized to identify differentially expressed proteins in 10 oral squamous carcinoma samples paired with their corresponding normal tissues. A total of 52 significantly and consistently altered proteins were identified with eight of these being reported for the first time in oral squamous carcinoma. Of the eight newly implicated proteins, RACK1 was chosen for detailed analysis. RACK1 was demonstrated to be up-regulated in cancer at both the mRNA and protein levels. Immunohistochemical examination showed that the enhanced expression of RACK1 was correlated with the severity of the epithelial dysplasia as well as clinical stage, lymph node involvement, and recurrence, which are known indicators of a relatively poor prognosis in oral squamous carcinoma patients. RNA interference specifically targeted to silence RACK1 could initiate apoptosis of oral squamous carcinoma cells. Taken together, the results indicate that RACK1 is up-regulated in oral squamous carcinoma, not only being closely related to cell proliferation and apoptosis but also linked to clinical invasiveness and metastasis in carcinogenesis. The observations suggest that RACK1 may be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of oral squamous carcinoma. Further this comprehensive strategy could be used for identifying other differentially expressed proteins that have potential to be candidate biomarkers of oral squamous carcinoma.

Human papillomavirus co-infection and survival in oral and oropharyngeal squamous cell carcinoma: A study in 235 Brazilian patients

Background: In addition to tobacco and alcohol consumption, some infectious pathogens such as human papillomavirus (HPV) have been proposed as carcinogenic factors in oral cancer. Objective: The objective of the study is to assess the possible influence of HPV detection in oral squamous cell carcinoma (OSCC). Materials and Methods: A PubMed search through April 2018, using the following Medical Subject Headings terms, was performed: “mouth neoplasms” and “papillomavirus infections.” Studies with findings on HPV detection in OSCCs were assessed. From 77 studies with full-text availability, 59 were excluded for several reasons: no usable/irrelevant data (32), tonsils, base of tongue and non-OSCC cases studies (26), and animal testing studies (1). The data were analyzed using statistical software RevMan 5.3 (The Cochrane Collaboration, Oxford, UK). For dichotomous outcomes, the estimates of effects of an intervention were expressed as odds ratios (ORs) using Haenszel–Mantel method with 95% confidence intervals. Results: Eighteen studies on HPV detection in OSCCs were included in this meta-analysis. The mean percentage of HPV detection in OSCC was 37.1%. Oral cancer patients showed a higher risk of being infected with HPV than controls (OR: 4.85) and they were more likely to be infected with high-risk HPV (OR: 11.46). A larger number of smokers had HPV-infected tumors (OR: 1.45). Younger age, gender, tobacco and/or alcohol consumption, tumor differentiation degree, tumor size (T-status), and lymph node metastasis (N-status) were factors that did not have a significant influence on HPV-infected oral cancers. Conclusion: HPV infection, especially of high-risk HPV, is more frequent in patients with OSCC.

HPV Associated Oral and Oropharyngeal Cancer