Head and mouth virus

It usually takes years after being infected with HPV for cancer to develop. It is unclear if having HPV alone is enough to cause oropharyngeal cancers, or if other factors such as smoking or chewing tobacco interact with HPV to cause these cancers. HPV is not known to cause other head and neck cancers, including those in the mouth, larynx, lip, nose, or salivary glands. Symptoms of oropharyngeal cancer may include a long-lasting sore throat, earaches, hoarseness, swollen lymph nodes, pain when swallowing, and unexplained weight loss.

Some people have no symptoms. If you have any symptoms that worry you, be sure to see your doctor right away. The HPV vaccine was developed to prevent cervical and other cancers of the reproductive system. The vaccine protects against the types of HPV that can cause oropharyngeal cancers, so it may also prevent oropharyngeal cancers.

Vaccination is not recommended for everyone older than age 26 years. However, some adults age 27 through 45 years who are not already vaccinated may decide to get the HPV vaccine after speaking with their doctor about their risk for new HPV infections and the possible benefits of vaccination. HPV vaccination in this age range provides less benefit, as more people have already been exposed to HPV. When used consistently and correctly, condoms and dental dams can lower the chance that HPV is passed from one person to another.

In addition, peer support can be important to address the general and specific survivorship needs of individual patients These innovations carry the promise of sustainably improving supportive care and empowerment of HNSCC survivors Measurement precision of HRQOL by PROMs can benefit from other data sources as biomarkers and from objective measures collected using, for example, wearable devices, such as a smart watch, that record and analyse physical activity One of the current major challenges is to make collected HRQOL data universally available to patients and clinicians in a meaningful way that will facilitate the design of treatment regimens and post-therapy decisions and indicate appropriate supportive care for the individual patient.

Advances in biotechnology, drug development, robotic surgery, radiotherapy approaches and molecular characterization of human cancers including HNSCC in the 21 st century were expected to lead to improved outcomes for patients with HNSCC. However, despite these advances, outcomes have remained mostly unchanged for the past few decades, especially for HPV-negative HNSCC, and short-term and long-term treatment-associated morbidities are still substantial.

Most patients still present with advanced-stage disease and are treated with platinum-based chemotherapy regimens that were approved by the FDA in The requirement for multidisciplinary care including, amongst others, head and neck surgery, radiation oncology, medical oncology, head and neck pathology, speech language pathology, nutrition, prosthodontics and oral medicine coupled with the rarity of HNSCC in most countries, underscores our recommendation that all patients with HNSCC should be treated in high-volume centres and by experienced multi-disciplinary teams.

Even when patients with HNSCC are treated in a multi-institutional chemoradiation clinical trial, the overall survival of those patients treated at centres that enroll more patients in trials in the USA was significantly greater than that of patients treated at institutions that enroll fewer patients In a pooled analysis of six randomized, controlled trials in Italy, survival was improved when patients with HNSCC were treated at high-case-volume centres compared with low-case-volume centers Despite improvements in treatment options, particularly the incorporation of immune checkpoint inhibitors into the standard of care, we also recommend that all patients with advanced, incurable HNSCC be offered the opportunity to participate in clinical trials that are based on a strong biological rationale.

Fortunately, numerous clinical trials are ongoing and precision medicine approaches are emerging. Barriers to widespread vaccination of all girls and boys prior to HPV infection include cost, general vaccine skepticism and concerns that administration of a vaccine against a sexually transmitted virus will encourage sexual activity.

We encourage clinicians who treat patients with HNSCC to partner with paediatricians, public health officials and politicians to increase HPV vaccination rates worldwide. Non-smokers who develop HPV-positive HNSCC generally survive their head and neck cancer, and clinical strategies to date have focused on identifying treatments that are associated with reduced morbidity.

The known toxicities of the EGFR inhibitor cetuximab are notably less than those of platinum chemotherapy. Ongoing and future research aimed at elucidating the immune profile of HPV-positive HNSCC is expected to help define therapeutic targets in this population. Mitigating the toxicities associated with standard of care, including platinum chemotherapy and radiation, for these patients remains an important objective.

Success stories include the recognition that HRAS mutations may serve as predictive biomarkers for treatment with farnesyl transferase inhibitors, such as tipifarnib , and evidence that oncogenic PIK3CA mutations are common and could be used to identify patients with HNSCC who are most likely to benefit from PI3K pathway inhibitors 69 , Although some centres are routinely evaluating the mutational profile of HNSCC tumours, the tumours in the majority of patients with HNSCC remain uncharacterized, even when these patients present with recurrent or metastatic disease.

Furthermore, the role of tumour mutational burden as a predictive biomarker for immunotherapy remains incompletely understood and efforts are underway to establish guidelines that are designed to harmonize tumour mutation burden evaluation and reporting Prospective, targeted sequencing, supported by efforts such as the American Association for Cancer Research Project Genie, aim to provide a publicly accessible international cancer registry of real-world data assembled through data sharing Importantly, single-cell transcriptomic analysis represents a powerful new tool for defining diverse intratumoral expression programmes and differences among tumours from different patients, as has been demonstrated in HNSCC , In addition, increased use of relevant preclinical models, including patient-derived xenografts , and organoids , should facilitate the translation of laboratory discoveries to patients with HNSCC.

The importance of the immune system in the development and treatment of HNSCC has long been recognized, leading to early efforts to treat this malignancy using strategies to activate endogenous immunity. The FDA approval of immune checkpoint inhibitors in for recurrent or metastatic disease, and for front-line treatment of inoperable or metastatic cancer in , definitively altered the landscape of HNSCC therapy and clinical trial opportunities.

For patients who benefit from these agents, responses seem to be durable 7 — 9. However, to date, only a subset of patients with HNSCC are expected to respond to immune checkpoint inhibitors, and reliable predictive biomarkers are needed.

Whereas PD1 and PDL1 inhibitors are generally well tolerated, CTLA4 inhibitors are associated with more toxicity , and it will be important to balance efficacy and toxicity when combining these agents. In addition, although adaptive immune cell therapies eg. CAR T cells and therapeutic vaccines are not FDA approved, they are under active investigation in head and neck cancer and represent a promising new avenue for therapy.

The era of immune-oncology has highlighted the limitations of traditional preclinical HNSCC models, including cell lines and xenografts derived from cell lines and patient tumours. Even though patient-derived xenografts are a more accurate model of the patient tumour than cell lines, the xenograft stroma largely consists of mouse cells and these models are generally grown in immunocompromised mice.

For example, a report of a syngeneic carcinogen-induced HNSCC tumour in immunocompetent mice demonstrates the ability of these models to assess responses to anti-CTLA4 antibodies Given the limitations of preclinical models to study immune perturbations, the development of novel clinical trial platforms in conjunction with immune profiling approaches offer opportunities to test the effect of novel immunotherapies in the clinical setting with minimal risk Nature Reviews Disease Primers thanks C.

Chung, C. Van Waes, A. Dietz, J. Hess, C. Bradford and the other, anonymous, reviewer s for their contribution to the peer review of this work. National Center for Biotechnology Information , U. Nat Rev Dis Primers. Author manuscript; available in PMC Mar Daniel E. Johnson , 1 Barbara Burtness , 2 C. Bauman , 5 and Jennifer R.

Julie E. Jennifer R. Author information Copyright and License information Disclaimer. Author contributions Introduction J. Copyright notice. The publisher's final edited version of this article is available at Nat Rev Dis Primers. See other articles in PMC that cite the published article. Abstract Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma HNSCC.

Introduction Head and neck squamous cell carcinomas HNSCCs develop from the mucosal epithelium in the oral cavity, pharynx and larynx and are the most common malignancies that arise in the head and neck Fig. Open in a separate window.

Figure 1. Epidemiology Incidence, prevalence and mortality HNSCC is the sixth most common cancer worldwide, with , new cases and , deaths in Fig. Figure 2. Global incidence of head and neck squamous cell carcinoma. Figure 3. Figure 4. Figure 5. Genomic alterations and key pathways There is a tremendous need to identify molecular biomarkers that can be used to predict progression of premalignant HNSCC lesions, prognosticate survival, reveal new targets for intervention and predict response to therapeutic agents.

Tumour microenvironment The tumour microenvironment TME in HNSCC is a complex and heterogeneous mix of tumour cells and stromal cells, which include endothelial cells, cancer-associated fibroblasts CAFs and immune cells. Immune evasion. The oral microbiome. Oral cavity tumours. Laryngeal tumours. EBV-positive nasopharyngeal tumours. Diagnosis Histopathology. Figure 6.

Tobacco and areca nut use. HPV vaccination. Secondary prevention Secondary prevention refers to the early detection of latent, asymptomatic disease and subsequent interventions to halt disease progression to a harmful state. Management The treatment approach to every individual patient is guided by anatomical subsite, stage, disease characteristics, functional considerations and patient wishes. Surgery, radiation and chemotherapy The principal modalities of curative therapy for locally or locoregionally confined HNSCC are resection, radiation and systemic therapy.

Immunotherapy Among patients with recurrent or metastatic HNSCC, some may be cured by salvage resection, re-irradiation particularly for nasopharyngeal cancer or metastatectomy particularly for HPV-positive cancer Fig. Figure 7. Survivorship With the increase in incidence and improved survival rates, more people have to cope with living beyond a diagnosis of HNSCC and its treatment see Box 1. Box 1. Patient experience. Moving forward An integrated approach to survivorship care in HNSCC survivors, including early rehabilitation, psychosocial care, lifestyle interventions and self-management, will likely be implemented in the next 5—10 years Outlook Advances in biotechnology, drug development, robotic surgery, radiotherapy approaches and molecular characterization of human cancers including HNSCC in the 21 st century were expected to lead to improved outcomes for patients with HNSCC.

Table 1. Current NCTN head and neck cancer trials. Immunotherapy The importance of the immune system in the development and treatment of HNSCC has long been recognized, leading to early efforts to treat this malignancy using strategies to activate endogenous immunity. Footnotes Competing interests D. References 1. Stein AP et al.

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Temporal space infections — These infections typically originate from the posterior maxillary molar teeth. Swelling may be limited to the preauricular region and an area over the zygomatic arch see Figure 8.

As infection progresses, the cheek, eyelids, and whole side of the face may be involved. Infection may extend directly into the orbit via the inferior orbital fissure and produce proptosis, optic neuritis, and abducens nerve palsy see Figure 9. Infratemporal space infections — An infratemporal space infection usually originates from the third maxillary molar tooth.

Clinically, marked trismus and pain are present, but very little swelling is observed early in the course. Late manifestations are similar to those of temporal space infections, including extension into the orbit through the inferior orbital fissure. Infection may also extend internally to involve an area close to the lateral pharyngeal wall, resulting in dysphagia.

Masticator space infections originating from the 3rd molar tooth. Horizontal view of the mouth showing ramus of the mandible, and the pterygoid and masseter muscles which are involved in mastication.

Infection may spread to 1, peritonsillar space; 2, pterygoid space; 3, masseteric space; 4, buccal space; 5, intraorally. Masticator space infection involving the right mandibular 3rd molar, showing marked swelling of the face and neck. Temporal space infections.

The temporal space is divided by the temporalis muscle into a superficial component enclosed by the masseter muscle and a deep component enclosed by the medial pterygoid muscle. Deep temporal space infection with spread to the right parotid space and the orbit. This patient developed right optic neuritis with permanent loss of vision. A, frontal view; B, lateral view showing pre-auricular swelling. Although an independent association between periodontal disease and atherosclerotic vascular disease is well recognized, a causal relationship has not been established.

Even though periodontal interventions result in a reduction in systemic inflammation and endothelial dysfunction in short-term studies, no evidence exists that they prevent the development of atherosclerotic vascular disease or its outcomes in the long term. Ann Intern Med. This is a landmark paper correlating the microbiology, clinical presentation, and anatomic inter-relationships of orofacial odontogenic infections.

Loesche, W. Infect Dis Clin N Am. This source contrasts the clinical manifestations, pathogenesis, and management of dental caries and periodontal disease. Unique association with Klebsiella pneumoniae infection among diabetic patients in Southeast Asia. Treatment includes hydration and intravenous antibiotics. Since suppurative parotitis may invade deep fascial spaces of the head and neck and is potentially life-threatening, outpatient management with oral antibiotics is not advised.

Initial empirical antimicrobial regimens are based on the expected microbiology and host factors, such as comorbid conditions and immunosuppression see Table III. The microbiology is quite variable and often polymicrobial involving both aerobic and anaerobic bacteria. Facultative gram-negative organisms, such as Enterobacteriaeae, H. Pigmented Prevotella and Porphyromonas spp. Step down therapy may be considered once the patient has improved and surgical management is deemed unnecessary.

The choice of oral regimens for step-down therapy should ideally be guided by culture and susceptibility data. Surgical incision and drainage should be implemented if there is no clinical response after 48 hours of treatment with empirical intravenous antibiotics.

Cross section view of the mouth at the level of the mandibular molar teeth, showing proximity of the parotic and peritonsillar spaces to the lateral or parapharyngeal space and structures.

Mycobacterium tuberculosis and non-tuberculous mycobacteria e. Brook, I. J Craniofac Surg. This is a comprehensive review with up-to-date microbiology. Am J Emerg Med. This source illustrates the life-threatening nature of suppurative parotitis with spread to the deep fascial spaces. Peritonsillar abscess. A large unilateral abscess is visible in the pharynx with prominent swelling of the soft palate and anterior pillar.

Imaging is not necessary to make the diagnosis of peritonsillar abscess but may be helpful in differentiating cellulitis from abscess and other deep neck space infections and to assess possible complications e. CT with contrast preferred reveals hypodense mass with ring enhancement within peritonsillar space. Magnetic resonance angiography MRA to evaluate vascular complications e. The first step is upper airway management to treat respiratory distress and prevent aspiration of abscess contents.

Needle aspiration should be attempted to decompress abscess and obtain pus for Gram stain, cultures, and susceptibility testing. This is performed in Trendelenburg position with topical anesthesia and under ultrasound guidance. Trial of empirical antibiotic therapy before definitive surgery if no evidence of airway compromise, severe trismus, or other complications.

Peritonsillar abscess is usually polymicrobial. Group A streptococcus S. Choices of initial empiric antimicrobial regimens are shown in Table IV. Subsequent therapy should be guided by culture data and susceptibility testing.

The choice of oral regimens for step-down therapy should be guided by culture and susceptibility data. Peritonsillar abscess may compromise the upper airway or spread into surrounding structures, including the masseter and pterygoid muscles, the lateral pharyngeal space, and the carotid sheath see Figure Spontaneous rupture of the abscess may cause asphyxiation or aspiration pneumonia.

Contrast-enhenced axial CT of the neck in a young adult with jugular venous thrombosis associated with a lateral pharyngeal space infection secondary to a right peritonsillar abscess. The common carotid arteries C are normal but the right internal jugular vein J is enlarged with a dense or enhancing wall surrounding the more lucent intraluminal clot arrow. Invasion by pathogenic bacteria e.

Rarely, peritonsillar abscess may also develop by hematogenous seeding of the salivary glands in the soft palate Weber glands , which directly communicate with the tonsils. Lateral pharyngeal space infection due to spread from a parotid or submandibular space infection bulging behind posterior tonsillar pillar rather than superior to the tonsil.

Severe tonsillopharyngitis e. A single double-blind randomized clinical trial in showed significant improvement in symptoms ability to swallow and length of hospital stay in the steroid group compared to placebo.

Confirmation with a larger study is needed before this can be routinely recommended. J Laryngol Otol. This is a prospective study of use of steroids for peritonsillar abscess. Powell, J, Wilson, JA. Clin Otolaryngol. This source provides the most up-to-date evidence-based review of peritonsillar abscess management. Ear Nose Throat J. This is a review of necrotizing fasciitis secondary to peritonsillar abscess. Deep neck space infections most commonly originate from a septic focus in mandibular molars, tonsils, parotid gland, deep cervical lymph nodes, paranasal sinuses, or mastoids.

These infections occupy three important spaces embedded within different layers of the deep cervical fascia: the submandibular space see Figure 15 , the lateral pharyngeal also known as parapharyngeal or pharyngomaxillary space see Figure 16 , and the retropharyngeal space see Figure Although rare in the post-antibiotic era, deep neck space infections are potentially life-threatening because of their proximity to the airway and vascular structures with potential spread into the carotid sheath, cavernous sinus, cranium, and the mediastinum see Figure 3.