AJCC staging of HPV-positive (p16+) oropharyngeal cancer [14].
\r\n\t
",isbn:"978-1-80355-637-6",printIsbn:"978-1-80355-636-9",pdfIsbn:"978-1-80355-638-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"8b1de69136c25696027635b9cc7ad76e",bookSignature:"Dr. Aneesa Moolla",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11567.jpg",keywords:"COVID-19, Dental Trauma, Telemedicine, Dentistry, Virtual Dental Consultations, Restorative Dentistry, Oral Health, Pandemic, Telehealth, Dental Emergency, Dental Injuries, Telehealth",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 25th 2022",dateEndSecondStepPublish:"February 22nd 2022",dateEndThirdStepPublish:"April 23rd 2022",dateEndFourthStepPublish:"July 12th 2022",dateEndFifthStepPublish:"September 10th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"A principal researcher with diverse interests spanning across multiple disease care continuums and a clinical supervisor in the field of dentistry.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"318170",title:"Dr.",name:"Aneesa",middleName:null,surname:"Moolla",slug:"aneesa-moolla",fullName:"Aneesa Moolla",profilePictureURL:"https://mts.intechopen.com/storage/users/318170/images/system/318170.png",biography:"Dr. Aneesa Moolla has extensive experience in the diverse fields of health care having previously worked in dental private practice, at the Red Cross Flying Doctors association, and in healthcare corporate settings. She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. 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From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"9588",title:"Clinical Concepts and Practical Management Techniques in Dentistry",subtitle:null,isOpenForSubmission:!1,hash:"42deab8d3bcf3edf64d1d9028d42efd1",slug:"clinical-concepts-and-practical-management-techniques-in-dentistry",bookSignature:"Aneesa Moolla",coverURL:"https://cdn.intechopen.com/books/images_new/9588.jpg",editedByType:"Edited by",editors:[{id:"318170",title:"Dr.",name:"Aneesa",surname:"Moolla",slug:"aneesa-moolla",fullName:"Aneesa Moolla"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"65848",title:"Large Molecule Fragmentation Dynamics Using Delayed Extraction Time-of-Flight Mass Spectroscopy",doi:"10.5772/intechopen.84407",slug:"large-molecule-fragmentation-dynamics-using-delayed-extraction-time-of-flight-mass-spectroscopy",body:'\nLarge molecules in general and in particular, polycyclic aromatic hydrocarbons (PAHs) are found in the terrestrial environment as well as in the interstellar medium abundantly [1]. They are primarily formed on earth by the incomplete combustion of organic molecules. The origin of Diffuse Interstellar Bands (DIBs), that are absorption features seen in the spectra of astronomical objects in optical and infrared wavelengths has been attributed to PAHs [2]. Considering the abundance of high energy radiation in the interstellar medium, it remains an interesting endeavor to understand the mechanism behind the survivability of PAHs in such environments. Because of such astronomical significance, the interaction of PAHs with photons and charged particles has seen renewed interest in the last couple of decades. Even in recent times, several results have been reported globally on the topic of ion-PAH collisions [3, 4, 5, 6]. In addition, detailed experiments are being carried out using synchrotron radiation sources [7]. High energy electron interaction with PAHs, on the other hand, has not been investigated in the context of radiation tolerance of PAHs.
\nHigh energy photon impact studies are often made using synchrotron radiation sources [8, 9, 10] with atoms or molecules as targets. Such mass spectrometric techniques along with the secondary electron selectivity methods like photoelectron-photoion coincidence (PEPICO) spectroscopy and threshold photoelectron-photoion coincidence (T-PEPICO) spectroscopy helps in determining the appearance energy and time scales of various dissociation channels of molecules very accurately. By modeling the line shape of the mass spectrum that arises due to slow decay, corresponding decay constant can be measured for microsecond range [11]. Longer decay times are probed using ion traps with variable extraction time [12]. It is essential to note that the excitation mechanism in conjunction with the appropriate electron spectrometer gives a very narrow range of internal energy left in the molecule. In particular, near the threshold, the internal energy is generally larger than the original thermal energy of the molecule, leading to resulting decay constants also range in a narrow band of values. Considering that the Arrhenius law decay rates are extremely sensitive to the internal energy, this factor very importantly implies that the decay rates with such secondary electron gated species will lie in a narrow range. Charged particle interaction with molecules will have a much broader range of internal energies and a precise value of decay constant cannot be obtained even with a suitable secondary electron energy gating. Hence modeling of exact decay curve for charged particle collision induced dissociation is deemed impractical. Moreover often minor fragmented peaks will interfere with the tail of mass spectrum due to isotopic effects or due to the presence of many hydrogen atoms in the molecule.
\nElectron impact ionization is one of the oldest mass spectrometric tools but it mainly focuses on identifying the possible ionization and fragmentation channels particularly between 70 and 100 eV energy. Typically, the mass spectrometric data available in the database is taken in this range, because ionization cross-section normally peaks in this region [13]. In past, several electron impact ionization investigations have been done mainly on inert gasses, diatomic or triatomic molecular gasses. Several experiments and modeling attempts have been made for such studies with electron energy up to few keV [14, 15, 16]. But such studies are very rare for larger molecules; the main reason is the complexity of a large number of decay channels, difficulties in separating indirect from direct ionization processes. For large molecules there are few attempts have been made in some specific cases for target specific energy loss modeling within the charged particle interaction with molecules [17].
\nThe stability of PAHs during the interaction of charged particles, cosmic rays and photon sources in the interstellar medium is of our interest [4, 7]. It has been shown conclusively that for charged particle interaction with naphthalene, the plasmon excitation is a major channel particularly at high velocities of projectile wherein the other processes have diminishing cross section [4]. It is also seen that acetylene (\n
The pulsed extraction of ions in a ToF setup can be used to analyze the evolution of a time-dependent population of various fragmentation channels. If the decay constants are in the range of \n
For detection of product ions we use a Wiley-McLaren type time-of-flight mass spectrometer [20] with the pulsed extraction technique. The experimental set-up with the data acquisition system is shown in Figure 1. This experimental set-up consists of pusher (labeled as \n
The developed experimental set-up.
Pulsing sequence used for delayed extraction time-of-flight mass spectrum.
Stainless steel (\n
Electron beams are very sensitive to electrode voltages and hence in a time of flight spectrometer used in electron impact studies, they need special arrangement to limit the effect of the extraction voltages on the pusher and puller. Usually, this can be achieved by pulsing the extraction voltages. Switching noise pickup on the detector channels are the major complications with this arrangement. The electron beam cannot be allowed to persist during the extraction process, failing to which the beam might cause a large number of secondary electrons produced due to the deflected beam hitting the electrodes and then causing additional undesired ionization events. While we extracting the recoil ions it becomes essential to blank the electron beam. For this purpose, the present experiment with electron impact ionization requires two sets of fast switches, one set for switching electron beam and the other for switching of pusher and puller simultaneously. By using commercial off the shelf power MOSFETs we built fast switches to achieve this. Very commonly used fast single output switches are detailed in few literature for various applications [21, 22, 23, 24]. Dual output fast pulsers for time-of-flight mass spectrometry are also available commercially, but are quite expensive generally.
\nIt is necessary to have a pair of switches which can operate in a synchronized manner to switch the pusher and puller plates in the spectrometer which enables us to control the extraction cycle accurately. We use a pair of fast power MOSFETs triggered in synchronism to achieve this. A brief schematic of the high voltage MOSFET switch circuit is as shown in Figure 3. In order to minimize the probability of damage to the external TTL pulse generator due to noise produced by the high voltage section of the circuit, the TTL pulse is passed through several logic gates. This pulse is then used to trigger a MOSFET driver (IC31415P) and the output of the driver is fed to a toroidal transformer with single primary (two turns) and a pair of secondary (five turns each). Gate of the main power MOSFET is controlled by each of the two outputs, triggers a pair of small signal MOSFETs (BS170) which in turn control the. We have tested the switch with voltages as high as \n
Schematic of high voltage MOSFET switch (push-pull).
High voltage MOSFET switch output (a) push-pull mode, (b) rise time
A pair of deflectors and an aperture in between are used to achieve the electron beam pulsing. A single output MOSFET switch is used for one of the deflectors closer to the electron gun and this switch was derived from the same circuit described above but by using only one branch and using a cascade of four identical MOSFETs to achieve pulsing ability for voltages as high as \n
For optimized geometry as well as voltages for ion trajectory (as shown in Figure 5a, we performed the Simulation of our time-of-flight mass spectrometer with SIMION8.0 [25]. We simulated conditions with as much as 2.5 mm displacement of the center of the interaction region along the ToF axis as well as in the direction perpendicular to the ToF axis (Figure 5b). From our simulation the collection efficiency is estimated by assuming a spherical distribution of the source of diameter 6 mm and assuming an rms velocity twice as large as the value of 300 K that is 480 μm/μs is as the worst case scenario and in all the cases, we could achieve 100\n
(a) Trajectory simulated for naphthalene (
Various projectile electron beam energy values with varying amounts of delay between the electron pulse-off and extraction pulse-on time are used for recording the Naphthalene mass spectra. The mass spectra obtained at different beam energies, as well as extraction delays, are systematically normalized to the single ionization peak area. For comparison between different beam energies and delay combinations, the area of each individual peak after such normalization could directly be considered.
\nA typical mass spectra is dominated by singly ionized naphthalene molecule followed by prominent peaks originating due to acetylene evaporation losses, as well as intact di-cation, and di-cation with \n
The mass spectrum of naphthalene(
For low-Z targets like hydrocarbons, the projectile energy dependence of the electron impact ionization process is very commonly known to peak at about 70–100 eV and at higher energy, the cross section varies as \n
Projectile electron beam energy dependence of different decay channel with zero delay time extraction. Decay channels are labeled as listed above.
Thus, we have considered the following decay channels for our analysis.
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
The loss of one or more H atom from the intact mono-cation is not shown explicitly in the list but is one of the most important channels. As observed by Gotkis et al., the primary decay channel for naphthalene is either H loss or acetylene loss [12]. It should be noted that the loss of multiple H and acetylene fragments are the prominent statistical decay modes for PAHs and therefore they can be very useful in understanding the dynamics of the internal degrees of freedom in PAHs. Acetylene loss is clearly the most useful channel to study from the data we present here. Higher order ionizations like double and triple ionization are low impact parameter processes and thus a detailed direct coulomb interaction model is more relevant in such cases. In this study our main goal is to explore the plasmon excitation which is a large impact parameter process and it is known to produce singly charged cations for the case of PAHs [26]. We expect strong dynamical and statistical effects in the singly charged naphthalene ions and the associated evaporation products like single and double acetylene loss in our case. Various decay channels are referred in the manuscript according to the numbers given in the list above.
\nJochims et al. are discussed the reaction sequence for acetylene loss and the formation of phenyl-acetylene \n
The first six decay channels are considered here with mono-cations and the rest may come from very energetic mono-cation or di-cation. Thus the processes governing the production of the latter decay channels can be treated as low impact parameter and high internal energy channels. And subsequently these decay channels are expected to have substantially large decay rates compared to the decay rates for mono-cations leading to decay channels ii and iii. This unique behavior is evident as shown in Figure 8a–c in which plot the relative intensity of all the decay channels at 250, 500 and 1000 eV electron impact energies. The very first clear observation is that the decay channels ii evolve very differently compared to the rest of the channels as a function of extraction delay and this can be seen in Figure 9a, b. The diacetylene loss channel show an increase in the yield fraction followed by a steady population or a slight decrease up to 5 \n
Various fragmentation channels of naphthalene at (a) 250 eV, (b) 500 eV, (c) 1000 eV electron impact energies. Decay channels are labeled as listed above.
(a) Decay channel ii (
The interaction energy for the formation of larger sized fragments according to reactions iv - viii needs to be well above 22 eV as discussed by Ruhl et al. [18]. The plasmon excitation is expected to peak at about 17 eV [26]. In the data for each beam energy, we observe that compared to the acetylene loss the decay channel iii peak shows a faster rate of change and this can be understood from the fact that the decay rate of channel iii is marginally higher than that of the acetylene loss channel. Interestingly we see a gradual decrease in the relative intensity of all the daughter channels as a function of projectile energy. We can assign two major possibly for the decay channel iii: [1] neutral acetylene evaporation from mono-cation and [2] the dissociation of \n
For PAHs in general and for naphthalene in particular a strong influence of the plasmon resonance excitation is known to be present. This effect has recently gained importance due to its possible role in the formation of molecular hydrogen and acetylene molecules in ISM and has been under investigation using far-UV photo-excitation as well as heavy ion-induced excitation. In this work, we have shown the effect of plasmon excitation under by high energy electron impact excitation. The time evolution of the acetylene evaporation, which is known to be a by-product of the plasmon excitation process, is measured for this study. A pulsed electron source along with the pulsed extraction of recoil ions using fast high voltage pulses is implemented and varying the extraction delay we observe the parent and daughter ion yields of naphthalene molecule is observed.
\nThe most dominant low energy channels commensurating with the excitation energy, in range of 7–8 eV leading to a total energy loss of 15–16 eV range is the decay channels leading to loss of acetylene and the loss of diacetylene. Acetylene loss shows much weaker energy dependence compared to the other channels which again is a well-known property of plasmon excitation. In the case of acetylene evaporation processes the time scales of few microseconds are seen and yields of acetylene evaporation population grow by about 20\n
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in the world [1]. The tonsils are the most common location in oropharyngeal malignancy. Despite being easily accessible to examination, its symptoms are usually ignored especially in early stages, leading to high morbidity and mortality. Traditionally oral and oropharyngeal cancers were attributed to smoking and alcohol abuse, but in more recent years there has been an increase in numbers due to high prevalence of Human papillomavirus (HPV) infection. The presence of HPV can alter the prognosis of the disease, and recently there was a change in the WHO classifications and TNM staging to reflect this [2]. Depending on the stage of the disease, treatment for oral and oropharyngeal cancers consists of surgery and/or chemoradiotherapy.
Traditionally smoking is considered the major factor in developing tonsil cancer. More than three quarters of oropharyngeal cancers are associated with tobacco use in all its forms (cigarettes, cigars, pipes, chewed tobacco). Secondhand smokers also have an increased risk of developing head and neck cancers. Alcohol is the second major risk factor in the etiology of tonsil cancer. Although studies have not shown a direct link between the use of alcohol alone in carcinogenesis, the combined effect of tobacco and alcohol has a synergic effect on the development of cancer cells [3].
In the last 10 years, HPV infection has been widely recognized as an important etiological factor in the development of head and neck squamous cell carcinomas. The development of PCR analysis or in situ hybridization has demonstrated the impact of HPV in oropharyngeal malignancy [1]. Gillison [4] was the first to show that HPV-positive oropharyngeal cancers have different molecular, clinical, and pathological traits than HPV-negative cancers. Although HPV is considered to play a vital role in most head and neck cancers, studies have only proven its impact in oropharyngeal cancers [5].
HPV is a double-stranded DNA oncovirus and is epitheliotropic, infecting the basal cells of the epithelium and can be found in up to 60% of squamous cell carcinomas of the oropharynx [6]. There are more than 150 isolated strains of HPV, but only two types 16 and 18 are most commonly linked to oropharyngeal cancers. The oncogenic effect of HPV is due to two proteins E6 and E7 that target the p53 and pRB (retinoblastoma) tumor suppressor genes of the infected cells making them vulnerable to mutations [7]. The loss of the pRB tumor suppressor determines the intranuclear accumulation of p16. p16 has a tumor suppressor role which normally would inhibit cell cycle but is overexpressed in HPV-positive tumors due to the action of E7. It is considered a useful marker in oropharyngeal cancers [8]. Due to the large body of evidence that suggest that HPV-positive and HPV-negative oropharyngeal cancers represent distinct subgroups of OPSCC, the National Comprehensive Cancer Network (NCCN) guidelines as of 2017 require HPV testing for all oropharyngeal tumors and that the HPV status must be included as a stratification factor [2]. The latest staging for oropharyngeal cancers takes into account the distinct groups of OPSCC, and because HPV-positive cancers tend to have a better prognosis, separate TNM staging systems are used [9, 10].
Dietary habits also play a role in carcinogenesis although harder to properly quantify. For example, iron deficiency may lead to an increased vulnerability of the oropharyngeal mucosa and decreased immune system. A diet low in fruits and vegetables can lead to a vitamin A and vitamin E deficiency that is associated with an increased risk of developing oropharyngeal malignancies. Poor oral hygiene can also be a risk factor especially for tobacco and alcohol users [11].
Oropharyngeal cancer is usually located in the tonsillar fossa, but extension to adjacent structures is common (Figure 1). Frequently tonsillar carcinoma extends downward to the tongue base along the glosso-tonsillar sulcus (Figure 2) and to the soft palate laterally. Laterally the tonsillar fossa is bounded by the superior constrictor muscle of the pharynx which offers some resistance to the spread of carcinoma. Extension past the superior constrictor muscle represents involvement of the parapharyngeal space with consecutive involvement of the pterygoid musculature or mandible locally advanced disease. Extension to the skull base is rare but possible.
Oral examination of a male patient with a left oropharyngeal tumor which infiltrates and deforms the tonsillar fossa as well as part of the soft palate, with ulceration and suprainfection.
Fiber-optic endoscopy of a male patient showing inferior spread of a left side oropharyngeal tumor towards the tongue base.
Due to its rich lymphatic drainage, lymph node involvement is present in about 70% of patients. The most common lymph node levels affected are level II and level III [12].
Distant metastasis from tonsillar cancer occurs in about 15–30% of cases; the most common sites are the lung, liver, and bones [13].
Tonsillar cancer may present with a variety of signs and symptoms. In the early stages, the patient is usually asymptomatic, or it can mimic some mild diseases like sore throat or acute tonsillitis. Patients usually complain of sore throat, unilateral otalgia, or a feeling of a mass in the throat. In advanced stages it can present with dysphagia. In latter stages the patient may present with trismus or bleeding from the mouth. If the tumor has ulcerations and necrosis, patients will usually complain of bad breath. The rich lymphatic drainage could mean that the first sign of disease is enlarged lymph nodes especially in the jugulodigastric region (group II). Such patients must be asked about weight loss, hoarseness, and odynophagia. A thorough patient history about tobacco and alcohol use and other known etiological factors (including known HPV infection) may raise suspicion of a malignant tumor. HPV-positive tumors will typically appear in younger nonsmoking patients.
Patients diagnosed with a tumor involving the oral and oropharyngeal regions must undergo a full ENT examination, with neck palpation, flexible endoscopy, and biopsy. After histological confirmation of the malignancy, imaging studies must be obtained to stage the tumor. Contrast CT scans represent the standard method for staging and should include the skull base, cervical region, thorax, and abdomen to possibly identify secondary tumors. Contrast-enhanced MRI is superior to CT in detecting soft tissue extension and involvement but may be influenced by dental foreign materials.
Staging of the disease is done by using the AJCC cancer staging system (Table 1) that uses three variables—primary tumor characteristics (T), lymph node involvement (N), and the existence of metastases (M).
Stage | T | N | M |
---|---|---|---|
I | T0-T2 | N0 | M0 |
T0-T2 | N1 | M0 | |
II | T0-T2 | N2 | M0 |
T3 | N0-N2 | M0 | |
III | T0-T3 | N3 | M0 |
T4 | N0-N3 | ||
IV | T Any | N Any | M1 |
AJCC staging of HPV-positive (p16+) oropharyngeal cancer [14].
Starting from 1 January 2017, all patients with oropharyngeal cancer should be tested for the presence of HPV, thus classifying them in one of two possible categories—HPV positive (p16INK4A+) and HPV negative. There is no current gold standard test, because all available testing methods were developed for cervical cancer, and not perfectly adapted for tonsillar cancer. However, p16 protein IHC is currently used for detecting HPV presence [15].
Tumor and lymph node characteristics are described in Tables 2 and 3, whereas the presence of distant metastases automatically stages the disease into the last and most severe stage—stage IV (Table 1).
Tumor | Characteristics |
---|---|
T0 | No primary tumor identified |
T1 | Tumor less than 2 cm in any dimension |
T2 | Tumor between 2 and 4 cm |
T3 | Tumor greater than 4 cm in any dimension or extension to lingual surface of the epiglottis |
T4 | = moderately advanced local disease—tumor invades the larynx, extrinsic muscles of the tongue, medial pterygoid muscles, hard palate, mandible or beyond |
AJCC tumor characteristics regarding HPV-positive (p16+) oropharyngeal carcinoma [14].
Lymph node (N) | Clinical N (cN) | Pathological N (pN) |
---|---|---|
Nx | Regional lymph nodes cannot be assessed | Regional lymph nodes cannot be assessed |
N0 | No regional lymph node metastasis | No regional lymph node metastasis |
N1 | One or more ipsilateral lymph nodes, none >6 cm | Metastasis in 4 or fewer lymph nodes |
N2 | Contralateral or bilateral lymph nodes, none >6 cm | Metastasis in more than 4 lymph nodes |
N3 | Lymph node(s) > 6 cm |
AJCC lymph node characteristics for staging of disease regarding HPV-positive (p16+) oropharyngeal cancer.
Treatment of oropharyngeal malignancy depends on the disease stage, but the principle that guides it is the same as in all cancer surgery: local disease control. Thus, with modern surgical and irradiation techniques, 5-year survival rates of almost 100% are attainable [16].
For the purpose of management protocol, oropharyngeal cancer is divided into early-stage (T1 and T2) and advanced diseases (T3 and T4). The latter are divided into resectable and non-resectable tumors. According to this, treatment for early-stage disease should be either surgery or radiation therapy with concurrent chemotherapy. Surgical treatment consists of excision of the primary tumor, either by a trans-oral approach or by external approach (lateral pharyngotomy or trans-mandibular approach by mandibular swing technique (Figures 3–5)).
External approach to a right side advanced (T4) oropharyngeal cancer which shows the neck dissection, with internal jugular vein and bifurcation of the common carotid artery visible inferior to the posterior belly of the omohyoid muscle, as well as the mandibulotomy—The creation of the mandibular “swing.”
External approach to a left side advanced oropharyngeal tumor, via mandibular “swing” demonstrating closure of the mandibulotomy using two titanium miniplates anchored with screws.
Extensive external approach to a left side advanced (T4) tumor of the oropharynx and hypopharynx extending to the bony cortex of the mandible—with modified radical neck dissection and lateral mandibulotomy, with the two resulting mandibular pieces being pulled apart at different angles so as to permit wider access.
Most oropharyngeal tumors are accessible by trans-oral approach. This is the least aggressive type of surgical approach, with the least morbidity. Auto-static mouth gags (McIver, Dingmann, etc.) permit good exposure of the surgical site, and excision by electrocautery, radiofrequency, and CO2 laser, and optical augmentation either using surgical loupes or operating microscopes permit tackling most of the T1 to T3 tumors [17].
Tumors extending downward to the epiglottis and hypopharynx (pyriform sinus) require an external approach, by lateral pharyngotomy. This approach provides access to the oro- and hypopharynx, as well as control of the cervical large blood vessels and lymph nodes [18, 19, 20].
Advanced tumors (T4), tumors which involve adjacent structures (extrinsic muscles of the tongue, larynx, mandible, pterygoid muscles, or hard palate), often require an even more aggressive external approach—by lateral mandibulotomy—the so-called mandibular swing technique. This approach permits access to the oral cavity, oropharynx, as well as hypopharynx and lateral cervical lymph nodes, parapharyngeal space, and masticator space and allows instrumentation of the entire oral cavity, making hard palate resections possible [21, 22].
Whichever surgical approach to the primary tumor the surgeon opts for, just as important as the complete excision of the tumor (the T) is the neck dissection. Tumors that do not pass the midline usually require ipsilateral lymph node dissection. However, bilateral neck dissection is sometimes required because of the vast network of lymphatics that drain the lateral pharyngeal area—most patients present with at least clinically N1 on diagnosis [23, 24].
The alternative to surgical excision of the tumor is external intensity-modulated radiation therapy (IMRT) with or without adjuvant chemotherapy. This procedure has similar outcomes compared to surgery in cases of early-stage tumors but is slightly inferior compared to surgery when addressing advanced tumors. The dose delivered to the surrounding tissues is responsible for the toxicity and late adverse effects of radiation therapy, such as osteoradionecrosis of the mandible, radiomucositis, xerostomia, dental cavities, and teeth avulsion [25]. These have a high impact on the patients’ quality of life; thus modern management of HPV-positive oropharyngeal cancer consists in trans-oral excision (with a rising trend towards robotic surgery) of the primary tumor with selective neck dissection followed by low-dose radiation therapy [25].
As HPV infection is a growing concern worldwide, cases of HPV-positive oral and oropharyngeal carcinoma become more frequently encountered. Treatment options for this type of malignancy follow the same principles as for non-HPV-positive squamous cell carcinoma of the oral cavity and pharynx, consisting in surgery for locoregional control of the primary tumor and regional lymph nodes and radiation therapy—either as a stand-alone option or as an adjuvant therapy following surgical excision.
However, particularities of HPV-positive oropharyngeal cancer have led to a separation of this pathologic entity from the rest of squamous cell carcinomas involving the oropharynx. These tumors have a better outcome following treatment and thus treatment options were de-escalated to offer the same outcome and 5-year survival as well as less morbidity and a better quality of life.
New perspectives in treating the chronic HPV infection as well as preventing this infection by introducing efficient vaccination programs that target girls and boys also offer a positive future perspective on reducing malignancies associated with this viral infection, including those affecting the oral cavity and pharynx.
"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges".
\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
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\\n\\nOA Publishing Fees
\\n\\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
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The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. 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He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. 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His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems.
\r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
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