Análise de polimorfismos e de expressão do gene p16INK4a em neoplasias cervicais

O câncer de colo do útero é o segundo carcinoma mais frequente em mulheres no mundo e um dos cânceres femininos mais incidentes no Brasil. Em lesões pré-malignas e malignas do colo uterino, a proteína p16INK4a, que participa do controle do ciclo celular, apresenta um aumento considerável de sua expressão, devido possivelmente à presença de oncoproteínas do papilomavírus humano (HPV). Dois polimorfismos no gene p16INK4a, p16 500C>G e p16 540C>T, estão localizados na região 3 não traduzida (3UTR), que está envolvida na regulação pós-transcricional da expressão gênica. O objetivo deste estudo foi avaliar possíveis associações entre os polimorfismos p16 500C>G e p16 540C>T e o desenvolvimento de neoplasias cervicais e/ou a severidade das lesões, considerando os níveis de expressão da proteína p16INK4a nas lesões cervicais e certos fatores de risco clássicos para o câncer cervical, incluindo a infecção pelo HPV. Para isso, foram selecionadas 567 mulheres residentes no Rio de Janeiro, 319 com citologia cervical alterada (grupo de casos) e 248 sem história prévia de alteração citológica do colo uterino (grupo de comparação). Amostras de sangue periférico de todas as participantes foram utilizadas na análise molecular dos polimorfismos p16 500C>G e p16 540C>T através da técnica de PCR-RFLP (reação em cadeia da polimerase - polimorfismo de comprimento de fragmento de restrição), usando as enzimas de restrição MspI e HaeIII, respectivamente. A expressão da proteína p16INK4a em 137 biópsias de mulheres pertencentes ao grupo de casos foi avaliada por imunohistoquímica. A detecção de DNA do HPV em células cervicais foi feita em todas as amostras do grupo de comparação e em 194 amostras do grupo de casos pela técnica de PCR, usando dois pares de oligonucleotídeos, MY09/MY11 e GP05+/GP06+. Os dois grupos de estudo se encontram em equilíbrio de Hardy-Weinberg. As distribuições genotípicas para p16 500C>G e p16 540C>T e as distribuições de combinações haplotípicas nos dois grupos não apresentaram diferenças significativas. A análise do subgrupo HSIL+câncer (casos com lesão intraepitelial de alto grau ou carcinoma invasivo) em comparação com o subgrupo LSIL (casos com lesão intraepitelial de baixo grau) revelou diferença significativa entre as distribuições das combinações haplotípicas (p = 0,036) e diferenças marginais entre as distribuições genotípicas para p16 500C>G (p = 0,071) e p16 540C>T (p = 0,051). O alelo p16 540G, em heterozigose ou homozigose (OR = 1,91, IC 95% = 1,08-3,37), e a combinação haplotípica p16 500C-540C 500G-540C (OR = 2,34, IC 95% = 1,202-4,555) mostraram-se associados com a severidade da lesões cervicais. Já o genótipo p16 540T/T (OR = 0,25, IC 95% = 0,08-0,79), e a combinação haplotípica p16 500C-540T 500C-540T (OR = 0,27, IC 95% = 0,088-0,827) exibiram papel protetor contra o desenvolvimento de lesões mais severas. As análises de interação entre os polimorfismos de p16INK4a e a expressão de p16 ou a infecção pelo HPV foram comprometidas pelo número reduzido de amostras analisadas. Não se observou qualquer interação entre os polimorfismos estudados e os fatores de risco clássicos para o câncer de colo uterino. Nossos resultados apontam para a importância dos polimorfismos do gene p16INK4a como marcadores de severidade da neoplasia cervical.

Dimensões relacionadas ao diagnóstico tardio do câncer do colo do útero: um estudo exploratório no Hospital do Câncer II / INCA

O objetivo deste estudo é o de conhecer e analisar a atenção em saúde de mulheres trabalhadoras com câncer do colo do útero avançado em tratamento no Hospital do Câncer II, no município do Rio de Janeiro. O estudo voltou-se para decifrar os diferentes momentos das trajetórias de vida e de trabalho dessas mulheres e relacioná-los com a procura dos serviços de saúde, estabelecendo relações com o acesso e a atenção à saúde. Constitui-se em um estudo exploratório, de natureza qualitativa, assentado em entrevistas e revisão teórico-bibliográfica. O aprofundamento teórico-empírico acerca deste tema buscou problematizar um objeto de estudo essencialmente relevante para o universo feminino, tendo em vista as altas taxas de incidência e mortalidade deste tipo de câncer no Brasil e no mundo sendo considerado, portanto, um problema de Saúde Pública. Os resultados apontam que o desconhecimento sobre o HPV e sobre a importância da realização do exame preventivo ainda é significativo entre as mulheres entrevistadas, o que aponta para a necessidade em priorizar o acesso à informação e a educação em saúde para o alcance de avanços no diagnóstico precoce. Também foram identificados como obstáculos na atenção em saúde, a sobrecarga de afazeres no cotidiano das mulheres, tendo em vista suas condições de vida e de trabalho e as dificuldades no acesso aos serviços de saúde.

乳头瘤病毒及协同因子与宫颈癌的关系

本研究旨在探讨宫颈癌前病变和宫颈癌的发生发展与人乳头瘤病毒及协同因子 (HSV ,CMV)的关系。对81例不同宫颈病变组织进行HPV16 / 18和HPV6 / 11原位杂交 ,同时对 10 3例不同宫颈病变组织用DNA扩增法检测HPV、HSV和CMV。结果表明病毒DNA原位杂交信号的分布与HE染色中挖空细胞的分布一致。HPV16 / 18与不同宫颈病变组织原位杂交阳性率平均为 5 1% ,HPV6 / 11的则为 6 4%。经PCR检测 ,HPV16 / 18、HPV6 / 11、HSV、CMV在不同宫

Distribution patterns of infection with multiple types of human papillomaviruses and their association with risk factors

Background: Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1, 810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. Principal Findings: The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (-31.1%), or were of mestizo (-24.6%) or black (-40.9%) ethnicity. Conclusions: According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2-4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.

Human papillomavirus detection in women with and without human immunodeficiency virus infection in Colombia

Background: HIV infection leads to a decreasing immune response, thereby facilitating the appearance of other infections, one of the most important ones being HPV. However, studies are needed for determining associations between immunodeficiency caused by HIV and/or the presence of HPV during the course of cervical lesions and their degree of malignancy. This study describes the cytological findings revealed by the Papanicolaou test, laboratory characteristics and HPV molecular profile in women with and without HIV infection. Methods: A total of 216 HIV-positive and 1,159 HIV-negative women were invited to participate in the study; PCR was used for the molecular detection of HPV in cervical samples. Statistical analysis (such as percentages, Chi-square test and Fisher's exact test when applicable) determined human papillomavirus (HPV) infection frequency (single and multiple) and the distribution of six types of high-risk-HPV in women with and without HIV infection. Likewise, a logistic regression model was run to evaluate the relationship between HIV-HPV infection and different risk factors. Results: An association was found between the frequency of HPV infection and infection involving 2 or more HPV types (also known as multiple HPV infection) in HIV-positive women (69.0% and 54.2%, respectively); such frequency was greater than that found in HIV-negative women (44.3% and 22.7%, respectively). Statistically significant differences were observed between both groups (p = 0.001) regarding HPV presence (both in infection and multiple HPV infection). HPV-16 was the most prevalent type in the population being studied (p = 0.001); other viral types had variable distribution in both groups (HIV-positive and HIV-negative). HPV detection was associated with <500 cell/mm(3) CD4-count (p = 0.004) and higher HIV-viral-load (p = 0.001). HPV-DNA detection, <200 cell/mm(3) CD4-count (p = 0.001), and higher HIV-viral-load (p = 0.001) were associated with abnormal cytological findings. Conclusions: The HIV-1 positive population in this study had high multiple HPV infection prevalence. The results for this population group also suggested a greater association between HPV-DNA presence and cytological findings. HPV detection, together with low CD4 count, could represent useful tools for identifying HIV-positive women at risk of developing cervical lesions.

The human papillomavirus and cancer: a multiphase study investigating preventative behaviours in young males

Background: The Human Papillomavirus (HPV) is one of the world’s most common sexually transmitted infections, and a causative factor of oropharyngeal, anal and penile cancers in males. Worldwide, an estimated 39,000 HPV-associated cancers occur each year in men. The highest rates of HPV infection are found in adults aged 18 to 28 years. Clinical evidence indicates that use of a condom in addition to obtaining the HPV vaccine provides the greatest protection from HPV infections. Aim: To explore young men’s attitudes, beliefs, and behavioural intention in relation to receiving the HPV vaccine and using a condom correctly and consistently. Collectively, both behaviours are linked to the prevention of HPV transmission and associated infections with HPV. Method: A multi- phase study, underpinned by the Theory of Planned Behaviour, involving a qualitative belief elicitation, pilot, and quantitative cross-sectional study was conducted. A belief elicitation (n=12) phase was used to generate items to include in a newly developed research instrument. Post pilot the research instrument was utilised in a cross sectional online survey to explore the attitudes, beliefs, and behavioural intention of young men (n= 359) with regard to receiving the HPV vaccine, and using a condom correctly and consistently. Data Collection: Data collection took place over a three month time frame. Male participants were recruited from a university in Southern Ireland via a student email system, as well as posting advertisements on numerous health, social and sports websites. Sample: Three hundred and fifty nine male participants aged 18- 28 years completed the online questionnaire. Data Analysis: Data were analysed using SPSS. Descriptive, correlational, multiple and hierarchical regression analysis were performed on the indirect and direct variables of the Theory of Planned Behaviour i.e. attitude, subjective norm, perceived behavioural control, and intention. Status variables were also included in descriptive analysis and hierarchical regressions. Findings are presented through text and graphical representation. Results: Alarming sexual health statistics identified that only 44.3% of participants always used a condom, and 78.6% never used a condom for oral sex. Furthermore, findings reveal that the constructs of the Theory of Planned Behaviour adequately measure male’s attitudes, beliefs and behavioural intention with regard to both behaviours. The Theory of Planned Behaviour has assisted in identifying how social pressures play an influential role in relation to males receiving the HPV vaccine. Attitudes presented as the most significant predictor of male’s intentions to use a condom correctly and consistently. Intention to perform both behaviours was identified as moderate to high. Conclusion: This study has contributed to the field of HPV research, as it is the first piece of research to explore preventative HPV behaviours i.e. receiving the HPV vaccine, and condom use, amongst young males, utilising the Theory of Planned Behaviour. A deeper understanding of young male’s attitudes, beliefs, and behavioural intention on this topic has been achieved. Additionally, a new robust research instrument has been constructed. Findings from this study will undoubtedly help in the implementation of the HPV vaccine in Ireland, as well as influence health promotion campaigns aimed at young males, addressing the topic of condom use.

Fabrication of Poly (D,L-Lactic-Co-Glycolic Acid) Microparticles for Improved Human Papillomavirus Vaccine Delivery

Human papillomavirus (HPV) is the leading cause of cervical cancer and the most prevalent sexually transmitted disease worldwide. HPV vaccines require a multi-dose regimen to provide immunity, contributing to low patient compliance. We addressed this problem by formulating biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) microparticles and assessing their viability for use in controlled-release vaccines. We hypothesized that we could alter fabrication parameters to produce 1-10 μm microparticles in order to encapsulate ovalbumin (OVA) and HPV virus-like particles (VLPs). Microparticles were fabricated using a double emulsion method and used to elicit an immune response in JAWSII cells. Our results contribute to knowledge of vaccine delivery mechanisms and controlled-release technology, and could contribute to the creation of a viable controlled-release HPV vaccine.

Human Papillomavirus and Oral Cancer: the International Agency for Research on Cancer Multicenter Study

Background: Human papillomavirus (HPV), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. To investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries. Methods: We recruited 1670 case patients (1415 with cancer of the oral cavity and 255 with cancer of the oropharynx) and 1732 control subjects and obtained an interview, oral exfoliated cells, and blood from all participants and fresh biopsy specimens from case patients. HPV DNA was detected by polymerase chain reaction (PCR). Antibodies against HPV16 L1, E6, and E7 proteins in plasma were detected with enzyme-linked immunosorbent assays. Multivariable models were used for case-control and case-case comparisons. Results: HPV DNA was detected in biopsy specimens of 3.9% (95% confidence interval [CI]=2.5% to 5.3%) of 766 cancers of the oral cavity with valid PCR results and 18.3% (95% CI=12.0% to 24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with valid PCR results. HPV DNA in cancer biopsy specimens was detected less frequently among tobacco smokers and paan chewers and more frequently among subjects who reported more than one sexual partner or who practiced oral sex. HPV16 DNA was found in 94.7% of HPV DNA-positive case patients. HPV DNA in exfoliated cells was not associated with cancer risk or with HPV DNA detection in biopsy specimens. Antibodies against HPV16 L1 were associated with risk for cancers of the oral cavity (odds ratio [OR]=1.5, 95% CI=1.1 to 2.1) and the oropharynx (OR=3.5, 95% CI=2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR=2.9, 95% CI=1.7 to 4.8) and the oropharynx (OR=9.2, 95% CI=4.8 to 17.7). Conclusions: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation.

Induction of tetraploidy through loss of p53 and upregulation of Plk1 by Human Papillomavirus type-16 E6

Cancer cells are insensitive to many signals that inhibit growth of untransformed cells. Here, we show that primary human epithelial cells expressing human papillomavirus (HPV) type-16 E6/E7 bypass arrest caused by the DNA-damaging drug adriamycin and become tetraploid. To determine the contribution of E6 in the context of E7 to the resistance of arrest and induction of tetraploidy, we used an E6 mutant unable to degrade p53 or RNAi targeting p53 for knockdown. The E6 mutant fails to generate tetraploidy; however, the presence of E7 is sufficient to bypass arrest while the p53 RNAi permits both arrest insensitivity and tetraploidy. We published previously that polo-like kinase 1 (Plk1) is upregulated in E6/E7-expressing cells. We observe here that abnormal expression of Plk1 protein correlates with tetraploidy. Using the p53 binding-defective mutant of E6 and p53 RNAi, we show that p53 represses Plk1, suggesting that loss of p53 results in tetraploidy through upregulation of Plk1. Consistent with this hypothesis, overexpression of Plk1 in cells generates tetraploidy but does not confer resistance to arrest. These results support a model for transformation caused by HPV-16 where bypass of arrest and tetraploidy are separable consequences of p53 loss with Plk1 required only for the latter effect.

Apoptosis is initiated in human keratinocytes exposed to signalling factors from microbeam irradiated cells.

PURPOSE: There is now no doubt that bystander signalling from irradiated cells occurs and causes a variety of responses in cells not targeted by the ionizing track. However, the mechanisms underlying these processes are unknown and the relevance to radiotherapy and risk assessment remains controversial. Previous research by our laboratory has shown bystander effects in a human keratinocyte cell line, HPV-G cells, exposed to medium from gamma irradiated HPV-G cells. The aim of this work was to investigate if similar mechanisms to those identified in medium transfer experiments occurred in these HPV-G cells when they are in the vicinity of microbeam irradiated cells. Demonstration of a commonality of mechanisms would support the idea that the process is not artifactual. MATERIALS AND METHODS: HPV-G cells were plated as two separate populations on mylar dishes. One population was directly irradiated using a charged particle microbeam (1 - 10 protons). The other population was not irradiated. Bystander factor-induced apoptosis was investigated in both populations following treatment by monitoring the levels of reactive oxygen species and mitochondrial membrane potential using fluorescent probes. Expression of the anti-apoptotic protein, bcl-2, and cytochrome c were determined, as well as apoptosis levels. RESULTS: Microbeam irradiation induced increases in reactive oxygen species and decreases in mitochondrial membrane potential at 6 h post-exposure, increased expression of bcl-2 and cytochrome c release at 6.5 h and increased apoptosis at 24 h. CONCLUSION: This study shows that similar bystander signalling pathways leading to apoptosis are induced following microbeam irradiation and following medium transfer. This demonstrates that the mechanisms involved are common across different radiation qualities and conditions and indicates that they may be relevant in vivo.

Clinical and immunohistochemical assessment of vulval intraepithelial neoplasia following photodynamic therapy using a novel bioadhesive patch-type system loaded with 5-aminolevulinic acid

Background: The work in this study appraised photodynamic treatment (PDT) as a treatment method for vulval intraepithelial neoplasia (VIN) using a novel bioadhesive patch to deliver aminolevulinic acid. An analysis of changes in expression of apoptotic and cell cycle proteins (p53, p21, Mdm2, Blc-2, Bax, Ki-67) in response to PDT was evaluated. Methods: PDT was performed using non-laser light, either as a one or two-cycle treatment, with clinical and pathological assessment following after 6 weeks. Twenty-three patients with 25 VIN lesions underwent 49 cycles of PDT Patches were designed to conform to uneven vulval skin and contained 38 mg cm(-2) aminolevulinic acid. Assessment was carried out at 6 weeks post-treatment. Patient-based treatment assessment, along with clinical and pathological changes, were monitored. Immunohistochemical staining was used to elucidate a possible biomolecular basis for induced cellular changes. Results: Most patients (52%) reported a symptomatic response, with normal pathology restored in 38% of lesions. The patch was easy to apply and remove, causing minimal discomfort. Fluorescence inspection confirmed protoporphyrin accumulation. Pain during implementation of PDT was problematic, necessitating some form of local analgesia. Changes in expression of cell cycle and apoptotic-related proteins suggested involvement of apoptotic pathways. Down regulation of p21 and inverse changes in Bcl-2 and Bax were key findings. Conclusion: Treatment of VIN lesions using a novel bioadhesive patch induced changes in cell cycle and apoptotic proteins in response to PDT with possible utilisation of apoptotic pathways. The efficacy of PDT in treating VIN could be improved by a better understanding of these apoptotic mechanisms, the influence of factors, such as HPV status, and of the need for effective pain management.

Compromised Spindle Assembly Checkpoint due to Altered Expression of Ubch10 and Cdc20 in Human Papillomavirus Type 16 E6 and E7-Expressing Keratinocytes

Cells expressing human papillomavirus type 16 (HPV-16) E6 and E7 proteins exhibit deregulation of G(2)/M genes, allowing bypass of DNA damage arrest signals. Normally, cells with DNA damage that override the G(2) damage checkpoint would precociously enter mitosis and ultimately face mitotic catastrophe and apoptotic cell death. However, E6/E7-expressing cells (E6/E7 cells) have the ability to enter and exit mitosis in the presence of DNA damage and continue with the next round of the cell cycle. Little is known about the mechanism that allows these cells to gain entry into and exit from mitosis. Here, we show that in the presence of DNA damage, E6/E7 cells have elevated levels of cyclin B, which would allow entry into mitosis. Also, as required for exit from mitosis, cyclin B is degraded in these cells, permitting initiation of the next round of DNA synthesis and cell cycle progression. Proteasomal degradation of cyclin B by anaphase-promoting complex/cyclosome (APC/C) is, in part, due to elevated levels of the E2-conjugating enzyme, Ubch10, and the substrate recognition protein, Cdc20, of APC/C. Also, in E6/E7 cells with DNA damage, while Cdc20 is complexed with BubR1, indicating an active checkpoint, it is also present in complexes free of BubR1, presumably allowing APC/C activity and slippage through the checkpoint.

Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes

A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future.

Monochloroacetic acid and 60% salicylic acid as a treatment for simple plantar warts:effectiveness and mode of action

Monochloroacetic acid crystals and 60% salicylic acid ointment was found to be more effective than placebo as a treatment for simple plantar warts in a double blind study on 57 patients. Nineteen (66%) patients in the active treatment group compared with five (18%) patients in the placebo group were cured after 6 weeks (P = 0.002). The active treatment was associated with a significantly higher cure rate 6 months after entry (P = 0.04). Treatments were well tolerated. IgG or IgM antibodies or both to human papilloma virus (HPV) types 1 or 2 or both were detected significantly more frequently in the actively treated group 6 weeks after entry (P = 0.0005). Twelve (50%) patients considered to be cured had no detectable secondary immune response. Our results suggest that cure does not depend primarily on the humoral system but rather on mechanical destruction of wart tissue, or occurs as a result of cell mediated immunity.

Human papillomavirus related head and neck cancer survival: A systematic review and meta-analysis

Human Papillomavirus (HPV) related oropharyngeal squamous cell carcinomas (OPSCCs) are reported to have improved prognosis and survival in comparison to other head and neck squamous cell cancers (HNSCCs). This systematic review and meta-analysis examines survival differences in HPV-positive HNSCC and OPSCC subtypes including tonsillar carcinoma in studies not previously investigated. Four electronic databases were searched from their inception till April 2011. A random effects meta-analysis was used to pool study estimates evaluating disease-specific (death from HNSCC), overall (all-cause mortality), progression-free and disease-free (recurrence free) survival outcomes in HPV-positive vs. HPV-negative HNSCCs. All statistical tests were two-sided. Forty-two studies were included. Patients with HPV-positive HNSCC had a 54% better overall survival compared to HPV-negative patients HR 0.46 (95% CI 0.37-0.57); the pooled HR for tonsillar cancer and OPSCC was 0.50 (95% CI 0.33-0.77) and HR 0.47 (95% CI 0.35-0.62) respectively. The pooled HR for disease specific survival was 0.28 (95% CI 0.19-0.40); similar effect sizes were found irrespective of the adjustment for confounders, HPV detection methods or study location. Both progression-free survival and disease-free survival were significantly improved in HPV-positive HNSCCs. HPV-positive HNSCCs and OPSCCs patients have a significantly lower disease specific mortality and are less likely to experience progression or recurrence of their cancer than HPV-negative patients; findings which have connotations for treatment selection in these patients.