Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: An epidemic of viral‐induced carcinoma?

Näsman, Anders; Attner, Per; Hammarstedt, Lalle; Du, Juan; Eriksson, Mikael; Giraud, G; Ährlund-Richter, Sofie; Marklund, Linda; Romanitan, Mircea; Lindquist, David; Ramqvist, Torbjörn; Lindholm, Johan; Sparén, Pär; Ye, Weimin; Dahlstrand, Hanna; Munck‐Wikland, Eva; Dalianis, Tina

doi:10.1002/ijc.24339

Cited by 637 publications

(573 citation statements)

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“…In this study, we found an HPV prevalence of 24.3% in our cohort, which is lower than the prevalence in OSCC and tonsillar cancer reported for the USA (45-83%) 4,5 or northern Europe (26-93%), 5,23,24 but comparable to data for central Europe (14-33%) [25][26][27] . We considered HPV-association of samples when high risk HPV-DNA was detected along with p16INK4a expression.…”

Section: Discussioncontrasting

confidence: 68%

CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma

et al. 2016

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Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OSCC) are clinical and biological distinct from their HPV-unrelated counterparts. Patients with HPV-related OSCC display improved prognosis and therefore we investigated possible immune cell infiltrations associated with this tumor phenotype. We retrospectively analyzed a randomly selected cohort of 140 OSCC for presence of immune cells and HPV by immunohistochemistry and PCR followed by beadbased hybridization (Luminex technology). HPV prevalence was 24.3% as determined by positive staining of p16INK4a and detection of high risk HPV-DNA. We found significantly higher numbers of CD56 positive (CD561) cells in tumor and surrounding microenvironment in HPV-associated compared to HPV-negative OSCC (t-test: p 5 0.004 and p 5 0.002). For the entire cohort presence of CD561 cells was associated with increased overall survival independent from HPV (Kaplan-Meier: p 5 0.002; Cox regression: p 5 0.042). Presence of CD561 cells also correlated with a better outcome in HPV-negative and especially in HPV-negative OSCC with alcohol consumption 2 standard drinks per day (Kaplan-Meier: p 5 0.05 and p 5 0.003). Immunofluorescence localization of granular Granzyme B (GZMB) within CD561 cells and coexpression of CD16 and CD56 suggests that detected CD561 cells mainly represent cytotoxic Natural Killer (NK) cells. The fraction of potentially cytotoxic NK cells was significantly higher in HPV-associated compared to HPV-negative OSCC (Mann-Whitney-U-Test: p 5 0.011). The elevated abundance and activity of cytotoxic NK cells in OSCC with HPV driven carcinogenesis might contribute to favorable outcome in HPV-related OSCC.Head and neck cancer (HNC, comprising cancers of the oral cavity, lip, pharynx, nasopharynx and larynx) is ranking at position seven of newly diagnosed cancers and cause of cancer death worldwide, with 4.8% of total cancer incidence and 4.6% of total cancer mortality. 1 In particular oropharyngeal squamous cell carcinomas (OSCC) are related to high risk human papillomavirus (HPV) infection, which is accepted to be causally connected to HNC. 2,3 A recently published metaanalysis demonstrates a rising incidence of HPV1 OSCC in the United States from 21% (pre-1990), to 51% (1990-1999), to 65% (2000-2013). 4 Patients with HPV-associated OSCC show lower levels of disease recurrence and progression compared to patients with HPV-negative OSCC. Even with good loco regional tumor control, patients with HPV-associated OSCC have similar rates of distant metastases as patients with HPVnegative OSCC. Further efforts are needed to understand clinical and biological features of this distinct disease. 2,5,6 Molecular basis of HPV-associated cancers differ from their HPVunrelated counterparts. 3 Pathways related to cell cycle control or apoptosis (commonly affected by mutations in HPVnegative cancers) are silenced at protein level by HPVoncoproteins (mainly E6 and E7). It has been speculated that lower levels of genetic alterations contribute to better treat...

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Section: Discussioncontrasting

confidence: 68%

CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma

et al. 2016

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“…Recent surveys from the US and Western Europe indicate an increase in the incidence of oropharyngeal cancers, particularly those of the tonsil and base of tongue [28][29][30] accumulating evidence supports the role of HPV infections in driving these upward trends [31][32][33][34][35]. As reported by others [1] HPV-positive HNSCC tends to be of oropharyngeal origin, diagnosed at a later stage, and found in younger individuals.…”

Section: Discussionmentioning

confidence: 76%

Human Papillomavirus-Associated Head and Neck Squamous Cell Carcinoma Survival: A Comparison by Tumor Site and Initial Treatment

Salazar

Smith

Garg

et al. 2013

Head and Neck Pathol

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Recent evidence suggests that human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) patients have better survival than HPV-negative patients. However, it is unclear if similar patterns for survival exist across different tumor sites, and whether HPV-associated prognosis is modified by type of treatment. We prospectively tested 222 histologically confirmed HNSCC primary tumors for HPV DNA by PCR and HPV E6/E7 RNA by RT-PCR prior to treatment at a large urban health center. Cox proportional hazard ratio models were constructed to assess HPV-associated differences in overall and disease-specific survival adjusting for clinical and demographic covariates. HPV detection varied significantly by primary HNSCC tumor site, from 35 % for oropharynx, to 25 % for hypopharynx, 5 % for larynx, and 3 % for oral cavity (p \ 0.0001), with HPV16 accounting for the majority (95 %) of HPV-positive tumors. The hazard-risk of overall and disease-specific death comparing HPV16-positive versus negative oropharyngeal HNSCC was reduced by 74 and 89 %, respectively (p values \ 0.05), and was independent of other prognostic indicators; no statistically significant changes in outcomes were observed for non-oropharyngeal HNSCC sites. Prediction of overall survival was better with combined DNA and RNA HPV16 positive PCR detection. There was no difference in HPV16-associated survival whether patients received either surgery or (chemo)radiotherapy as their initial treatment modality. Improved HPV-associated HNSCC survival is limited to Electronic supplementary material The online version of this article

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“…Incidence rates for these sites were highest among blacks and higher among nonHispanics and men than among Hispanics and women. 84,85 HPV-associated SCCHN tends to have distinct characteristics. Clinically, patients diagnosed with HPV-associated SSCHN demonstrate improved disease-specific survival.…”

Section: Role Of Chemotherapy In Human Papilloma Virus-associated Heamentioning

confidence: 99%

The Role of Chemotherapy in the Management of Patients with Head and Neck Cancer

Savvides

2010

Seminars in Plastic Surgery

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Recent advances in the management of patients with head and neck cancer point to an expanding role of chemotherapy, resulting in an increased involvement of the medical oncologist in the multidisciplinary care of these patients. This review focuses on patients with squamous cell carcinoma of the oral cavity, pharynx, and larynx. A comprehensive review of the clinical trial data that have defined new standards of care and a detailed presentation of widely used chemotherapeutic regimens, including both cytotoxic and molecularly targeted agents, are presented. Information on human papilloma virusassociated squamous cell cancer of the head and neck is presented, and implications in the clinical management of this subgroup of patients based on the epidemiologic and pathologic characteristics are discussed.KEYWORDS: Cancer of the head and neck, chemotherapy, squamous cell carcinoma Approximately 48,000 new cases of head and neck cancer were expected in the United States in 2009 alone, 1 and more than 600,000 new cases will be diagnosed worldwide. Head and neck cancer accounts for 3 to 4% of all cancer diagnoses in Western countries, 2,3 and its incidence is higher in southeast Asia and in Africa where it accounts for 8 to 10% of all cancers. 4 Overall, head and neck cancer represents the eighth most common cause of cancer death.Historically, treatment of patients with squamous cell carcinoma of the head and neck (SSCHN) has primarily been driven by surgical interventions and continued advances in radiation therapy (RT) treatment planning and delivery. In this setting of complex treatment algorithms, recent advances in the management of patients with head and neck cancer point to an expanding role of chemotherapy and therefore an increased involvement of the medical oncologist in the multidisciplinary care of these patients.The scope of this review is to provide a comprehensive description of expanding chemotherapeutic options, including both cytotoxic and molecularly targeted agents, that are applicable to patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx. Data on patients diagnosed with cancer of the nasopharynx will be presented separately because of its distinct etiology, pathology, and response to treatment modalities.Chemotherapy alone does not have curative potential. As a result, it does not have a defined role

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Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: An epidemic of viral‐induced carcinoma?

Cited by 637 publications

References 32 publications

CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma

CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma

Human Papillomavirus-Associated Head and Neck Squamous Cell Carcinoma Survival: A Comparison by Tumor Site and Initial Treatment

The Role of Chemotherapy in the Management of Patients with Head and Neck Cancer

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