HPV-positive oropharyngeal cancer

HPV-positive oropharyngeal cancer
Specialty	Oncology

Human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) also known as HPV16+ oropharyngeal cancer or HPV+OPC is a recognized subtype of oropharyngeal squamous cell carcinomas (OSCC), associated with the HPV type 16 virus (HPV16). Historically cancer of the oropharynx (throat) was associated with the use of alcohol and tobacco, but the majority of cases are now associated with the HPV virus. HPV+OPC differs in a number of respects to OPC not associated with HPV (HPV-OPC), as is considered a separate disease. HPV has long been associated with cancers in the anogenital region, but in 2007 was also recognised as a cause of oropharyngeal cancer. HPV is common among healthy adults and is largely transmitted through sexual contact, but tobacco use increases the risk of cancer. Detection of a tumour suppressor protein, known as p16, is commonly used to diagnose an HPV associated OPC. The extent of disease is described in the standard cancer staging system, using the AJCC TNM system, using the T stage (size and extent of tumour), N stage (extent of involvment of regional lymph nodes) and M stage (whether there is spread of the disease outside the region or not, and combined into an overall stage from I–IV. In 2016, for the first time a separate staging system was developed for HPV+OPC distinct from HPV-OPC.

Anatomy

Anatomy of oropharynx and surrounding structures

The oropharynx, at the back of the mouth, forms a circle and includes the the base of the tongue, the tonsils, the soft palate, and the walls of the pharynx. It lies between the mouth (oral cavity to the front, and the hypopharynx (laryngopharynx) behind that separates it from the voice box (larynx), behind.

Causation

Electron micrograph of Human Papilloma Virus

Most mucosal squamous cell head and neck cancers, including oropharyngeal cancer (OPC), have historically been attributed to tobacco and alcohol use. However this pattern has changed considerably since the 1980s. Human papillomavirus (HPV)-positive cancer (HPV+OPC) incidence has been increasing while HPV-negative (HPV-OPC) cancer incidence is declining, a trend that is estimated to increase further in coming years. Since there are marked differences in clinical presentation and treatment relative to HPV status, HPV+OPC is now viewed as a distinct biologic and clinical condition.

Human HPV has long been implicated in the pathogenesis of several anogenital cancers including those of the anus, vulva, vagina, cervix, and penis. In 2007 it was also implicated by both molecular and epidemiological evidence in cancers arising outside of the anogenital tract, namely oral cancers. HPV infection is common among healthy individuals, and is acquired largely through sexual contact. Although less data is available, prevalence of HPV infection is at least as common among men as among women, with 2004 estimates of about 27% among US women aged 14–59.

HPV oral infection precedes the development of HPV+OPC. Slight injuries in the mucous membrane serve as an entry gate for HPV, which thus works into the basal layer of the epithelium. People testing positive for HPV type 16 virus (HPV16) oral infection have a 14 times increased risk of developing HPV+OPC. Immunosuppression seems to be an increased risk factor for HPV+OPC. Individuals with TGF-β1 genetic variations, specially T869C, are more likely to have HPV16+OPC. TGF-β1 plays an important role in controlling the immune system. In 1993 it was noted that patients with human papillomavirus (HPV)-associated anogenital cancers had a 4-fold increased risk of tonsillar squamous-cell carcinoma. Although evidence suggests that HPV16 is the main cause of OPC in humans not exposed to smoking and alcohol, the degree to which tobacco and/or alcohol use may contribute to increase the risk of HPV+OPC has not always been clear but it appears that both smoking and HPV infection are independent and additive risk factors for developing OPC. Human herpesvirus-8 infection can potentiate the effects of HPV-16.

Mechanism

An increased risk of HPV+OPC is observed more than 15 years after HPV exposure, pointing to a slow development of the disease, similar to that seen in cervical cancer. HPV associated cancers are caused by the expression of HPV's E6 and E7 proteins that bind to and inactivate tumor suppressor proteins p53 and retinoblastoma protein (pRB), respectively, leading to malignant transformation of HPV infected cells. The biology of HPV+OPC is distinct from that of HPV-OPC, with P53 degradation (inactivated by E6 instead of by genetic mutation), pRB pathway inactivation (by E7 instead of Cyclin D1 amplification). Also the tumor suppressor protein p16 (cyclin-dependent kinase inhibitor 2A) is upregulated (over-expression of p16 instead of inactivation due to reduced negative feedback from pRB). The tonsillar epithelia (palatine and lingual) share similar nonkeratinization characteristics with the cervix, where HPV infection plays the major role in cases of cervical cancer.

Diagnosis

HPV+OPC is usually diagnosed at a more advanced stage than HPV-OPC. Genetic signatures of HPV+ and HPV- OPC are different. HPV+OPC is associated with expression level of the E6/E7 mRNAs and of p16. Nonkeratinizing squamous cell carcinoma strongly predicts HPV-association. HPV16 E6/E7-positive cases are histopathologically characterized by their verrucous or papillary (nipple like) structure and koilocytosis of the adjacent mucosa. Approximately 15% of HNSCCs are caused by HPV16 infection and the subsequent constitutive expression of E6 and E7, and some HPV-initiated tumors may lose their original characteristics during tumor progression. High-risk HPV types may be associated with oral carcinoma, by cell-cycle control dysregulation, contributing to oral carcinogenesis and the overexpression of mdm2, p27 and cathepsin B.

HPV+OPC is not merely characterized by the presence of HPV-16. Only the expression of viral oncogenes within the tumor cells plus the serum presence of E6 or E7 antibodies is unambiguously conclusive. There is not a standard HPV testing method in head and neck cancers, both in situ hybridization (ISH) and polymerase chain reaction (PCR) are commonly used. Both methods have comparable performance for HPV detection, however it is important to use appropriate sensitivity controls. Staining of the tissue for p16 is frequently used as a cost effective surrogate for HPV in OPC, compared to ISH or PCR.

Staging

Staging is generally by the AJCC TNM (Tumour, Nodes, Metastases) system. HPV+OPC has been treated similarly to stage-matched and site-matched unrelated OPC, but its unique features, which contrast smoking-related HPV-OPC head and neck cancers, for which patients' demographics, comorbidities, risk factors, and carcinogenesis differ markedly, suggest that a distinct staging system be developed to more appropriately represent the severity of the disease and its prognosis. Standard AJCC TNM staging, such as the seventh edition (2009) while predictive for HPV-OPC has no prognostic value in HPV+OPC The 8th edition of the AJCC TNM Staging Manual (2016) incorporates this specific staging for HPV+OPC. Current treatment guidelines do not account for the different outcomes observed in HPV+OPC. Consequently less intensive (de-intensification) use of radiotherapy or chemotherapy, as well as specific therapy, is under investigation, enrolling HPV+OPC in clinical trials to preserve disease control and minimise morbidity in selected groups based on modified TNM staging and smoking status.

HPV+ cancer of the oropharynx are staged as (AJCC 8th ed. 2016): Tumour stage

• T0 no primary identified
• T1 2 cm or less in greatest dimension
• T2 2–4 cm
• T3 >4 cm, or extension to lingual surface of epiglottis
• T4 moderately advanced local disease, invading larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible or beyond

Nodal stage

• Nx regional lymph nodes cannot be assessed
• N0 no regional lymph nodes involved
• N1 1 or more ipsilateral nodes involved, less than 6 cm
• N2 contralateral or bilateral lymph nodes, less than 6 cm
• N3 lymph node(s) larger than 6 cm

Clinical stage

• Stage I: T0N1, T1–2N0–1
• Stage II: T0–2N2, T3N–2
• Stage III: T0–3N3, T4N0-3
• Stage IV: any metastases (M1)

However the published literature and ongoing clinical trials use the older seventh edition that does not distinguish between HPV+OPC and HPV-OPC - see Oropharyngeal Cancer - Stages. The T stages are essentially similar between AJCC 7 and AJCC 8. with two exceptions. Tis (carcinoma in situ) has been eliminated and the division of T4 into substages (e.g. T4a) has been removed. The major changes are in the N stages, and hence the overall clinical stage. N0 remains the same, but as with the T stage, substages such as N2a have been eliminated. Invasion by the tumour beyond the capsule of the lymph node (extracapsular extension OR ECE) has been eliminated as a staging criterion. This results in a HPV+OPC tumour being given a lower stage than if it were HPV-OPC. For instance a 5 cm tumour with one ipsilateral node involved that is 5 cm in size but has ECE would be considered T3N3bM0 Stage IVB if HPV- but T3N1M0 Stage II if HPV+.

Treatment

The goals of care are to optimise survival and locoregional disease control, and prevent spread to distant areas of the body (metastasis), while minimising short and long term morbidity. There is no high quality Level I evidence from prospective clinical trials in HPV+OPC, therefore treatment guidelines must rely on data from treatment of OPC and from some subsetting of those studies. Treatment for OPC has traditionally relied on radiotherapy, chemotherapy and/or other systemic treatments, and surgical resection. Depending on stage and other factors treatment may include a combination of modalities. The mainstay has been radiotherapy in most cases. a pooled analysis of published studies suggested comparable disease control between radiation and surgery, but higher complication rates for surgery +/- radiation. Ideally a single modality approach is preferred, since triple modality is associated with much more toxicity, and a multidisciplinary team in a large centre with high volumes is recommended.

Surgery

Historically, surgery provided the single approach to head and neck cancer. Surgical management of OPC carried significant morbidity with a transcervical approach (via the neck) and often involving mandibulotomy (splitting the mandible). Improvements in surgical techniques have allowed many tumours to be removed (resected) by a transoral approaches (through the mouth). This approach has proven safety, efficacy and tolerability, and include two main minimally invasive techniques, transoral robotic surgery (TORS) and transoral laser microsurgery (TLM). No direct comparisons of these two techniques have been conducted, and clinical trials in head and neck cancer such as ECOG 3311 allow either. They are associated with substantial postoperative morbidity, depending on extent of resection but compared to older techniques have shorter hospital stay, faster recovery, less pain, and less need for gastrostomy or tracheostomy, and less long term effects, which are minimal in the absence of postoperative radiation, or chemoradiation. TORS has the practical advantage that angled telescopes and rotating robotic surgical arms provide better line of sight. Outcomes of minimally invasive procedures also compare favourably with more invasive ones. In early stage disease, including involvement of neck nodes, TORS produces a 2 year survival of 80–90 %. TLM similarly, is reported to have a five year survival of 78  % and local control rates of 85–97 %. In addition to early disease, minimally invasive surgery has been used in advanced cases, with up to 90 % local control and disease specific survival. Postoperative swallowing was excellent in 87 %, but long term dysphagia was associated with larger (T4) cancers, especially if involving the base of the tongue.

The details of the surgical approach depend on the location and size of the primary tumour and its N stage. Neck dissection to examine the draining lymph nodes may be carried out simultaneously or as a second staging procedure. For tumours of the tonsil and lateral pharyngeal wall, and clinically node negative (N0) disease, dissection of the neck typically involves levels 2–4 ipsilaterally. Where nodes are involved clinically, dissection will depend on the location and size of the node or nodes. In the case of tongue base primaries, close to the midline, bilateral dissection is recommended.

An advantage of a primary surgical approach is the amount of pathological information made available, including grade, margin status, and degree of involvement of lymph nodes. This may change the staging, as up to 40 % of patients may have a different postoperative pathological stage compared to their preoperative clinical stage. In one study, 24 % had their stage reduced (downstaged), which may impact subsequent decision making, including reduction in intensity and morbidity.

Adjuvant postoperative therapy

Data on the use of radiation is largely confined to studies on the overall population of patients with head and neck cancer, rather than specific studies of HPV+OPC. Despite surgical excision, in the more advanced cases local and regional recurrence of the cancer, together with spread outside of the head and neck region (metastases) are frequent. The risk of subsequent recurrent disease is highest in those tumours where the pathology shows tumour at the margins of the resection (positive margins), multiple involved regional lymph nodes and extension of the tumour outside of the capsule of the lymph node (extracapsular extension). The addition of postoperative radiation reduces the frequency of such recurrences. The addition of another modality of treatment is referred to as adjuvant (literally helping) therapy. Consequently many of these patients have been treated with adjuvant radiation, with or without chemotherapy. In the above series of reports of minimally invasive surgery, many (30–80 %) patients received adjuvant radiation. However, functional outcomes were worse if radiation was added to surgery and worst if both radiation and chemotherapy were used.

Radiotherapy

Intensity modulated radiation therapy (IMRT) can provide good control of primary tumours while preserving excellent control rates, with reduced toxicity to salivary and pharyngeal structures. IMRT has a two year disease free survival between 82 and 90 %, and a two year disease specific survival up to 97 % for stage I and II.

Reported toxicities include dry mouth (xerostomia) 18 % (grade 2); difficulty swallowing (dysphagia) 15 % (grade 2); subclinical aspiration up to 50  % (reported incidence of aspiration pneumonia approximately 14  %); hypothyroidism 28–38 % at three years {may be up to 55 % depending on amount of the thyroid gland exposed to over 45 Gy radiation; esophageal stenosis 5 %; osteonecrosis of the mandible 2.5 %; and need for a gastrostomy tube to be placed at some point during or up to one year after treatment 4 % (up to 16 % with longer follow up). However altered fractionation schemes, such as RTOG 9003 and RTOG 0129 have not conferred additional benefit.

Radiation dose recommendations are largely based on older clinical trials with few HPV+OPC patients, making it difficult to determine the optimum dose for this group. A common approach uses 70 Gy bilaterally and anteriorly, such as RTOG 9003 (1991–1997) and RTOG 0129 (2002–2005). For lateralized tonsil cancer unilateral neck radiation is usually prescribed, but for tongue base primaries bilateral neck radiation is more common, but unilateral radiation may be used where tongue base lesions are lateralised.

No new guidelines dealing specifically with HPV+OPC have yet been developed, outside of clinical trials. Indirect data suggests the efficacy of less intense treatment. A retrospective analysis of advanced (N+) HPV+OPC suggested 96 % 5 year local control with deintensified radiation of 54 Gy and concurrent cisplatin based chemotherapy. A prospective trial (ECOG 1308) demonstrated similar locoregional control with 54 Gy. Since long term toxicity is associated with radiation dose, determining the efficacy of lower and hence less morbid doses of radiation is a priority, since many HPV+ patients can be expected to have long term survival.

Radiation is commonly utilised in combination with chemotherapy, but also may be used as a single modality, especially in earlier stages, e.g. T1-T2, N0-1, and its use in later stages is being explored in clinical trials such as RTOG 1333 which compares radiation alone to radiation with with reduced chemotherapy, in non or light smokers. In the postoperative adjuvant setting, the addition of radiation to surgery is largely based on historical or retrospective studies, rather than high quality randomized clinical trials.

Chemotherapy

As with the radiotherapy data, most of the available knowledge on the efficacy of chemotherapy derives from the treatment of advanced head and neck cancer rather than specific studies of HPV+OPC. Cisplatin is considered the standard agent, and a survival advantage was seen for those patients who received radiation with concurrent cisplatin. Despite this no trials comparing cisplatin with other agents in this context have been conducted. The other agent that is widely used is Cetuximab, a monoclonal antibody directed at the epidermal growth factor receptor (EGFR). A 10 % survival advantage at three years was noted when cetuximab was given concurrently with radiation. The main toxicity is an acneiform rash, but it has not been compared directly to cisplatin in HPV+OPC, although RTOG 1016 is addressing this question. In advanced head and neck cancer, adding chemotherapy to radiation improves survival and locoregional control. Concurrent chemotherapy is also superior to chemotherapy alone (induction chemotherapy) followed by radiation.

Chemotherapy also has a role, combined with radiation, in the postoperative setting (adjuvant therapy). Generally it is used where the pathology of the resected specimen indicates features associated with high risk of locoregional recurrence (e.g. extracapsular extension through involved lymph nodes or very close margins). It has shown improved disease-free survival and locoregional control in two very similar clinical trials in such high risk patients, EORTC 22931 (1994–2000) and RTOG 9501 (1995–2000). However, for HPV+OPC patients, such extracapsular spread does not appear to be an adverse factor and the addition of chemotherapy to radiation in this group provided no further advantage. Since the sample size to detect a survival advantage is large, given the small number of events in this group, these studies may have been underpowered and the question of the utility of adding chemotherapy is being addressed in a randomized clinical trial (ADEPT) with two year locoregional control and disease free survival as the endpoint. The addition of chemotherapy to radiation increases acute and late toxicity. In the GORTEC trial, chemotherapy with docetaxel provided improved survival and locoregional control in locally advanced OPC, but was associated with increased mucositis and need for feeding by gastrostomy. Chemotherapy and radiation are associated with a risk of death of 3–4 % in this context. It is unclear whether the added toxicity of adding chemotherapy to radiation is offset by significant clinical benefit in disease control and survival.

It is thought that HPV+OPC patients benefit better from radiotherapy and concurrent cetuximab treatment than HPV-OPC patients receiving the same treatment, and that radiation and cisplatin induce an immune response against an antigenic tumour which enhances their effect on the cancer cells.

Choice of treatment approach

In the absence of high quality evidence comparing a primary surgical approach to other modalities, decisions are based on consideration of factors such as adequate surgical exposure and anatomically favourable features for adequate resection, post treatment function and quality of life. Such patient selection may enable them to avoid the morbidity of additional adjuvant treatment. In the absence of favourable surgical features the primary treatment of choice remains radiation with or without chemotherapy. Tumor characteristics which favour a non-surgiccal approach include invasion of the base of the tongue to the extent of requiring resection of 50 % or more of the tongue, pterygoid muscle involvement, extension into the parapharyngeal fat abutting the carotid, involvement of the mandible or maxilla or invasion of the prevertebral space.

The adequacy of surgical resection is a major factor in determining the role of postoperative adjuvant therapy. In the presence of a positive margin on pathological examination, most radiation oncologists recommend radiation to the primary site, and concurrent chemotherapy. A negative margin is more likely to be treted with lower doses and a smaller treatment volume. Also the removal of a bulky tumour may allow reduced dosage to adjacent uninvolved pharyngeal structures and hence less effect on normal swallowing.

The cancer outcomes (local control, regional control, and survival) for transoral resection followed by adjuvant therapy are comparable to primary chemoradiation, so that treatment decisions depend more on treatment-related morbidity, functional outcome, and quality of life. Patient factors also need to be taken into account, including general baseline functionality, smoking history, anesthesia risk, oropharyngeal function, swallowing and airway protection and potential for rehabilitation. Patient preference is equally important. Many clinical trials are under way focussing on deintensification, often with risk stratification, e.g. Low, Intermediate and High risk (see Fundakowski and Lango, Table I).

Clinical decisions also take into account morbidities, particularly if cancer outcomes are comparable for instance surgery is associated with a risk of bleeding between 5–10 %, and a 0.3 % risk of fatal postoperative haemorrhage. Surgery may also be complicated by dysphagia, and while most patients can tolerate a diet on the first postoperative day, long term use of a feeding tube has been reported as high as 10 %. Patients with larger tumours, involvement of base of tongue and requiring postoperative adjuvant therapy are more likely to require a long term feeding tube. Overall, function and quality of life appear relatively similar between surgery with postoperative radiation, and primary chemoradiation.

Anatomical considerations may also dictate preference for surgical or non-surgical approaches. For instance trismus, a bulky tongue, limited extension of the neck, prominent teeth, torus mandibularis (a bony growth on the mandible) or limited width of the mandible would all be relative contraindications to surgery.

Prognosis

The presence of HPV within the tumour has been realised to be an important factor for predicting survival since the 1990s. Tumor HPV status is strongly associated with positive therapeutic response and survival compared with HPV-negative cancer, independent of the treatment modality chosen. Response rates of over 80% are reported in HPV+ cancer and three-year progression free survival has been reported as 75–82 % and 45–57 %, respectively, for HPV+ and HPV- cancer, and improving over increasing time.

In RTOG clinical trial 0129, in which all patients with advanced disease received radiation and chemotherapy, a retrospective analysis at thee years identified three risk groups for survival (low, intermediate, and high) based on HPV status, smoking, and stage. 64% were HPV+ and all were in the low and intermediate risk group, with all non-smoking HPV+ patients in the low risk group. 82% of the HPV+ patients were alive at three years compared to 57% of the HPV- patients, a 58% reduction in the risk of death. Locoregional failure is also lower in HPV+, being 14% compared to 35% for HPV-. HPV positivity confers a 50–60 % lower risk of disease progression and death, but the use of tobacco is an independently negative prognostic factor. The majority of recurrences occur within the first year after treatment and are locoregional, but HPV does not reduce the rate of metastases, which are predominantly to the lungs. Even if recurrence or metastases occur, HPV positivity still confers an advantage.

A possible explanation is "the lower probability of occurrence of 11q13 gene amplification, which is considered to be a factor underlying faster and more frequent recurrence of the disease" Presence of TP53 mutations, a marker for HPV- OPC, is associated with worse prognosis. High grade of p16 staining is thought to be better than HPV PCR analysis in predicting radiotherapy response.

Tobacco use decreases response to therapy and is an independent risk factor for disease recurrence and overall survival increasing with the amount smoked, particularly if greater than 10 pack-years.

Epidemiology

The global incidence of pharyngeal cancer in 2013 was estimated at 136,000 cases. In the United States the estimated number of cases was 12,410 in 2008, 13,930 in 2013 and 17,000 for 2017. Of these cases, HPV-positive cancer (HPV+) has been increasing compared to HPV-negative cancer (HPV-).

HPV+ OPC patients tend to be younger than HPV- patients.The clinical presentation is also changing from the “typical” head and neck cancer patient with advanced age and major substance usage. By contrast patients with HPV+ cancer are younger (4th–6th decades), male (ratio 8:1) with no or only a minimum history of smoking, generally caucasian, reached higher education levels, are married, and have higher income. The presenting features are also different between HPV+ and HPV- OPC. HPV+ tumours have smaller primary lesions (less than 4 cm) but more advanced nodal disease resulting in higher TNM staging. This in turn may overestimate the severity.

Trends

A survey of 23 countries between 1983 and 2002 showed an increase in oropharyngeal squamous cell carcinoma that was particularly noticeable in young men in economically developed countries. Currently in the US there is a growing incidence of HPV associated oropharyngeal cancers,In the early 1980s HPV+ accounted for only 7.5% of cases in the US but by 2016 this was 70%, perhaps as a result of changing sexual behaviors, decreased popularity of tonsillectomies, improved radiologic and pathologic evaluation, and changes in classification. Tonsil and oropharyngeal cancers increased in male predominance between 1975 and 2004, despite reductions in smoking. The decline in smoking may be linked to the decreasing proportion of HPV negative cancers, while changes in sexual activity may be reflected in increasing proportion of HPV positive cancers. Recently, in the US, HPV associated OPC represent about 60% of OPC cases compared with 40% in the previous decade. By 2007, in the US, incidence of general OPC, including non-HPV associated, is 3.2 cases per 100,000 males/year and 1.9 per 100,000 all-sexes/year.

The increase in incidence of HPV associated OPC is also seen in other countries, like Sweden, with a 2007 incidence of over 80% for cancer in the tonsils, Finland and the Czech Republic. Partners of patients with HPV positive oropharyngeal cancer do not seem to have elevated oral HPV infection compared with the general population. In Australia incidence of HPV associated OPC is 1.56 cases per 100,000 males/year.

Prevention

Main article: HPV-associated oropharyngeal cancer awareness and prevention

Risk factors include a high number of sexual partners (25% increase >= 6 partners), a history of oral-genital sex (125% >= 4 partners), or anal–oral sex, a female partner with a history of either an abnormal Pap smear or cervical dysplasia, chronic periodontitis, and, among men, decreasing age at first intercourse and history of genital warts.

HPV vaccines have a theoretical potential to prevent oral HPV infection. A 2010 review study has found that HPV16 oral infection was rare (1.3%) among the 3,977 healthy subjects analyzed.

History

In 1983, it was first suggested that HPV might be the agent involved in the development of at least certain special types of oral cancers. In 2007 the World Health Organization stated HPV was a cause for oral cancers.

Bibliography

Articles

• Fakhry, Carole; Gillison, Maura L. (10 June 2006). "Clinical Implications of Human Papillomavirus in Head and Neck Cancers". Journal of Clinical Oncology (Review). 24 (17): 2606–2611. doi:10.1200/JCO.2006.06.1291. {{cite journal}}: Invalid |ref=harv (help)
• Mehanna, H.; Jones, T. M.; Gregoire, V.; Ang, K. K. (24 April 2010). "Oropharyngeal carcinoma related to human papillomavirus". BMJ (Editorial). 340 (7752): 879–880. doi:10.1136/bmj.c1439. JSTOR 40701677.
• Nguyen, N. P.; Chi, A.; Nguyen, L. M.; Ly, B. H.; Karlsson, U.; Vinh-Hung, V. (2009). "Human papillomavirus-associated oropharyngeal cancer: a new clinical entity". QJM (Review). 103 (4): 229–236. doi:10.1093/qjmed/hcp176. PMID 20015950.
• Psyrri, A.; Gouveris, P.; Vermorken, J. B. (2009). "Human papillomavirus-related head and neck tumors: clinical and research implication". Current Opinion in Oncology (Review). 21 (3): 201–205. doi:10.1097/CCO.0b013e328329ab64. PMID 19370803.
• Ramqvist, Torbjörn; Dalianis, Tina (November 2010). "Oropharyngeal Cancer Epidemic and Human Papillomavirus". Emerging Infectious Diseases. 16 (11): 1671–1677. doi:10.3201/eid1611.100452.
• Salem, A. (2010). "Dismissing links between HPV and aggressive tongue cancer in young patients". Annals of Oncology. 21 (1): 13–17. doi:10.1093/annonc/mdp380. PMID 19825879. {{cite journal}}: Invalid |ref=harv (help)
• Schwartz, S. M.; Daling, J. R.; Madeleine, M. M.; Doody, D. R.; Fitzgibbons, E. D.; Wipf, G. C.; Carter, J. J.; Mao, E.-J.; Huang, S.; Beckmann, A. M.; McDougall, J. K.; Galloway, D. A. (4 November 1998). "Oral Cancer Risk in Relation to Sexual History and Evidence of Human Papillomavirus Infection". JNCI Journal of the National Cancer Institute. 90 (21): 1626–1636. doi:10.1093/jnci/90.21.1626.
• Sinha, Parul; Lewis, James S.; Piccirillo, Jay F.; Kallogjeri, Dorina; Haughey, Bruce H. (15 July 2012). "Extracapsular spread and adjuvant therapy in human papillomavirus-related, p16-positive oropharyngeal carcinoma". Cancer. 118 (14): 3519–3530. doi:10.1002/cncr.26671.
• Smith, E.; Ritchie, J.; Summersgill, K.; Klussmann, J.; Lee, J.; Wang, D.; Haugen, T.; Turek, L. (Feb 2004). "Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers". International Journal of Cancer. Journal International Du Cancer. 108 (5): 766–772. doi:10.1002/ijc.11633. ISSN 0020-7136. PMID 14696105.
• Sturgis, E.; Cinciripini, P. (Oct 2007). "Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers?". Cancer. 110 (7): 1429–1435. doi:10.1002/cncr.22963. ISSN 0008-543X. PMID 17724670. {{cite journal}}: Invalid |ref=harv (help)
• Tachezy, R (May 2005). "HPV and other risk factors of oral cavity/oropharyngeal cancer in the Czech Republic". Oral Diseases. 11 (3): 181–185. doi:10.1111/j.1601-0825.2005.01112.x. PMID 15888110. {{cite journal}}: Invalid |ref=harv (help)
• Tezal, Mine; Sullivan Nasca, Maureen; Stoler, Daniel L.; Melendy, Thomas; Hyland, Andrew; Smaldino, Philip J.; Rigual, Nestor R.; Loree, Thom R. (1 April 2009). "Chronic Periodontitis−Human Papillomavirus Synergy in Base of Tongue Cancers". Archives of Otolaryngology–Head & Neck Surgery. 135 (4): 391. doi:10.1001/archoto.2009.6. PMID 19380363.
• Tezal, M.; Sullivan, M. A.; Hyland, A.; Marshall, J. R.; Stoler, D.; Reid, M. E.; Loree, T. R.; Rigual, N. R.; Merzianu, M.; Hauck, L.; Lillis, C.; Wactawski-Wende, J.; Scannapieco, F. A. (10 September 2009). "Chronic Periodontitis and the Incidence of Head and Neck Squamous Cell Carcinoma". Cancer Epidemiology Biomarkers & Prevention. 18 (9): 2406–2412. doi:10.1158/1055-9965.EPI-09-0334. PMID 19745222.
• Westra, W. H. (2009). "The Changing Face of Head and Neck Cancer in the 21st Century: the Impact of HPV on the Epidemiology and Pathology of Oral Cancer". Head and Neck Pathology. 3 (1): 78–81. doi:10.1007/s12105-009-0100-y. PMC 2807531. PMID 20596995. {{cite journal}}: Invalid |ref=harv (help)

Human Papilloma Virus (HPV)

• Adelstein, D. J.; Rodriguez, Cristina P. (February 3, 2010). "Human Papillomavirus: Changing Paradigms in Oropharyngeal Cancer". Current Oncology Reports. 12 (2): 115–120. doi:10.1007/s11912-010-0084-5. PMID 20425596. {{cite journal}}: Invalid |ref=harv (help)
• Agoston, E. .; Robinson, S. .; Mehra, K. .; Birch, C. .; Semmel, D. .; Mirkovic, J. .; Haddad, R. .; Posner, M. .; Kindelberger, D. .; Krane, J. F.; Brodsky, J.; Crum, C. P. (2010). "Polymerase chain reaction detection of HPV in squamous carcinoma of the oropharynx". American Journal of Clinical Pathology. 134 (1): 36–41. doi:10.1309/AJCP1AAWXE5JJCLZ. PMID 20551264.
• Cristina Mazon, Renata; Rovigatti Gerbelli, Thaís; Benatti Neto, Carlos; de Oliveira, Maria Rita Brancini; Antonio Donadi, Eduardo; Guimarães Gonçalves, Maria Alice; Garcia Soares, Edson; Patrícia Klay, Carla; Tersariol, Ivarne; Aparecida Pinhal, Maria; Resende, Luis; Pienna Soares, Christiane (February 2011). "Abnormal cell-cycle expression of the proteins p27, mdm2 and cathepsin B in oral squamous-cell carcinoma infected with human papillomavirus". Acta Histochemica. 113 (2): 109–116. doi:10.1016/j.acthis.2009.08.008.
• D'Souza, Gypsyamber; Gross, Neil D.; Pai, Sara I.; Haddad, Robert; Anderson, Karen S.; Rajan, Shirani; Gerber, Jennifer; Gillison, Maura L.; Posner, Marshall R. (10 August 2014). "Oral Human Papillomavirus (HPV) Infection in HPV-Positive Patients With Oropharyngeal Cancer and Their Partners". Journal of Clinical Oncology. 32 (23): 2408–2415. doi:10.1200/JCO.2014.55.1341.
• Elmofty, S.; Patil, S. (2006). "Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: Characterization of a distinct phenotype". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 101 (3): 339–345. doi:10.1016/j.tripleo.2005.08.001. PMID 16504868. {{cite journal}}: Invalid |ref=harv (help)* Gillison, M. L.; Koch, W. M.; Capone, R. B.; Spafford, M.; Westra, W. H.; Wu, L.; Zahurak, M. L.; Daniel, R. W.; Viglione, M.; Symer, D. E.; Shah, K. V.; Sidransky, D. (May 2000). "Evidence for a causal association between human papillomavirus and a subset of head and neck cancers". Journal of the National Cancer Institute. 92 (9): 709–720. doi:10.1093/jnci/92.9.709. ISSN 0027-8874. PMID 10793107.
• Frisch, M.; Biggar, R. (1999). "Aetiological parallel between tonsillar and anogenital squamous-cell carcinomas". The Lancet. 354 (9188): 1442–3. doi:10.1016/S0140-6736(99)92824-6. PMID 10543674.
• Guan, X.; Sturgis, E.; Lei, D.; Liu, Z.; Dahlstrom, K.; Wei, Q.; Li, G. (2010). "Association of TGF-beta1 genetic variants with HPV16-positive oropharyngeal cancer". Clinical Cancer Research. 16 (5): 1416–1422. doi:10.1158/1078-0432.CCR-09-2877. PMC 2831118. PMID 20179236.
• Jung, A.; Briolat, J.; Millon, R.; De Reyniès, A.; Rickman, D.; Thomas, E.; Abecassis, J.; Clavel, C.; Wasylyk, B. (2009). "Biological and clinical relevance of transcriptionnally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma". International Journal of Cancer. Journal International Du Cancer. 126 (8): 1882–1894. doi:10.1002/ijc.24911. PMID 19795456.
• Klussmann, J.; Mooren, J.; Lehnen, M.; Claessen, S.; Stenner, M.; Huebbers, C.; Weissenborn, S.; Wedemeyer, I.; Preuss, S.; Straetmans, J. M. J. A. A.; Manni, J. J.; Hopman, A. H. N.; Speel, E. -J. M. (Mar 2009). "Genetic signatures of HPV-related and unrelated oropharyngeal carcinoma and their prognostic implications". Clinical Cancer Research. 15 (5): 1779–1786. doi:10.1158/1078-0432.CCR-08-1463. ISSN 1078-0432. PMID 19223504.
• Kreimer, Aimée R.; Bhatia, Rohini K.; Messeguer, Andrea L.; González, Paula; Herrero, Rolando; Giuliano, Anna R. (January 2010). "Oral Human Papillomavirus in Healthy Individuals: A Systematic Review of the Literature". Sexually Transmitted Diseases: 1. doi:10.1097/OLQ.0b013e3181c94a3b. PMID 20081557.
• Lajer, C. B.; Buchwald, C. V. (2010). "The role of human papillomavirus in head and neck cancer". APMIS. 118 (6–7): 510–519. doi:10.1111/j.1600-0463.2010.02624.x. PMID 20553531.
• Lassen, P. (2010). "The role of Human papillomavirus in head and neck cancer and the impact on radiotherapy outcome". Radiotherapy and Oncology. 95 (3): 371–380. doi:10.1016/j.radonc.2010.04.022. PMID 20493569. {{cite journal}}: Cite has empty unknown parameter: |1= (help); Invalid |ref=harv (help)
• Lohavanichbutr, P.; Houck, J.; Fan, W.; Yueh, B.; Mendez, E.; Futran, N.; Doody, D.; Upton, M.; Farwell, D.; Schwartz, S. M.; Zhao, L. P.; Chen, C. (Feb 2009). "Genome-wide gene expression profiles of HPV-positive and HPV-negative oropharyngeal cancer: potential implications for treatment choices". Archives of Otolaryngology—Head & Neck Surgery. 135 (2): 180–188. doi:10.1001/archoto.2008.540. ISSN 0886-4470. PMC 2761829. PMID 19221247.
• Mannarini, L.; Kratochvil, V.; Calabrese, L.; Gomes Silva, L.; Morbini, P.; Betka, J.; Benazzo, M. (2009). "Human Papilloma Virus (HPV) in head and neck region: review of literature". Acta Otorhinolaryngologica Italica. 29 (3): 119–126. PMC 2815356. PMID 20140157.
• Martinez, I.; Wang, J.; Hobson, K.; Ferris, R.; Khan, S. (Jan 2007). "Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas". European Journal of Cancer (Oxford, England : 1990). 43 (2): 415–432. doi:10.1016/j.ejca.2006.09.001. ISSN 0959-8049. PMC 1847595. PMID 17079134. {{cite journal}}: Cite has empty unknown parameter: |1= (help)
• Michl, P; Pazdera, J; Prochazka, M; Pink, R; Stosova, T (2010). "Human papillomavirus in the etiology of head and neck carcinomas" (PDF). Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 154 (1): 9–12. doi:10.5507/bp.2010.004. PMID 20445705.
• Robinson, M.; Sloan, P.; Shaw, R. (2010). "Refining the diagnosis of oropharyngeal squamous cell carcinoma using human papillomavirus testing". Oral Oncology. 46 (7): 492–496. doi:10.1016/j.oraloncology.2010.02.013. PMID 20227331. {{cite journal}}: Cite has empty unknown parameter: |1= (help)
• Schlecht, N.; Burk, R.; Adrien, L.; Dunne, A.; Kawachi, N.; Sarta, C.; Chen, Q.; Brandwein-Gensler, M.; Prystowsky, M.; Childs, G.; Smith, R. V.; Belbin, T. J. (Nov 2007). "Gene expression profiles in HPV-infected head and neck cancer". The Journal of Pathology. 213 (3): 283–293. doi:10.1002/path.2227. ISSN 0022-3417. PMID 17893858.
• Smeets, S.; Van Der Plas, M.; Schaaij-Visser, T.; Van Veen, E.; Van Meerloo, J.; Braakhuis, B.; Steenbergen, R.; Brakenhoff, R. (2010). "Immortalization of oral keratinocytes by functional inactivation of the p53 and pRb pathways". International Journal of Cancer. Journal International Du Cancer. 128 (7): 1596–605. doi:10.1002/ijc.25474. PMID 20499310.
• Syrjänen, S. (2004). "HPV infections and tonsillar carcinoma". Journal of Clinical Pathology. 57 (5): 449–455. doi:10.1136/jcp.2003.008656. PMC 1770289. PMID 15113849. {{cite journal}}: Cite has empty unknown parameter: |1= (help); Invalid |ref=harv (help)
• Syrjänen, Kari; Syrjänen, Stina; Lamberg, Matti; Pyrhönen, Seppo; Nuutinen, Juhant (December 1983). "Morphological and immunohistochemical evidence suggesting human papillomavirus (HPV) involvement in oral squamous cell carcinogenesis". International Journal of Oral Surgery. 12 (6): 418–424. doi:10.1016/S0300-9785(83)80033-7. PMID 6325356.
• Underbrink, M.; Hoskins, S.; Pou, A.; Albrecht, T. (2008). "Viral interaction: a possible contributing factor in head and neck cancer progression". Acta Oto-Laryngologica. 128 (12): 1361–1369. doi:10.1080/00016480801965001. PMID 18607925.
• Vidal, L.; Gillison, M. (2008). "Human papillomavirus in HNSCC: recognition of a distinct disease type". Hematology Oncology Clinics of North America. 22 (6): 1125–1142, vii. doi:10.1016/j.hoc.2008.08.006. PMID 19010263. {{cite journal}}: Invalid |ref=harv (help)
• Weinberger, P.; Yu, Z.; Kountourakis, P.; Sasaki, C.; Haffty, B.; Kowalski, D.; Merkley, M.; Rimm, D.; Camp, R.; Psyrri, A. (Sep 2009). "Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma: Validation of three-class hypothesis". Otolaryngology-Head and Neck Surgery: official journal of American Academy of Otolaryngology-Head and Neck Surgery. 141 (3): 382–389.e1. doi:10.1016/j.otohns.2009.04.014. ISSN 0194-5998. PMID 19716018.
• Yamakawa-Kakuta, Y; Kawamata, H; Doi, Y; Fujimori, T; Imai, Y (15 September 2009). "Does the expression of HPV16/18 E6/E7 in head and neck squamous cell carcinomas relate to their clinicopathological characteristics?". International Journal of Oncology. 35 (05): 983–988. doi:10.3892/ijo_00000412. PMID 19787251. {{cite journal}}: Cite has empty unknown parameter: |1= (help)

Diagnosis and staging

• Chenevert, J; Seethala, RR; Barnes, EL; Chiosea, SI (April 2012). "Squamous cell carcinoma metastatic to neck from an unknown primary: the potential impact of modern pathologic evaluation on perceived incidence of human papillomavirus-positive oropharyngeal carcinoma prior to 1970". The Laryngoscope. 122 (4): 793–796. doi:10.1002/lary.21899. PMID 22252715.
• Lydiatt, William M.; Patel, Snehal G.; O'Sullivan, Brian; Brandwein, Margaret S.; Ridge, John A.; Migliacci, Jocelyn C.; Loomis, Ashley M.; Shah, Jatin P. (March 2017). "Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual". CA: A Cancer Journal for Clinicians. 67 (2): 122–137. doi:10.3322/caac.21389.
• O'Sullivan, Brian; Huang, Shao Hui; Su, Jie; Garden, Adam S; Sturgis, Erich M; Dahlstrom, Kristina; Lee, Nancy; Riaz, Nadeem; Pei, Xin; Koyfman, Shlomo A; Adelstein, David; Burkey, Brian B; Friborg, Jeppe; Kristensen, Claus A; Gothelf, Anita B; Hoebers, Frank; Kremer, Bernd; Speel, Ernst-Jan; Bowles, Daniel W; Raben, David; Karam, Sana D; Yu, Eugene; Xu, Wei (April 2016). "Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study". The Lancet Oncology. 17 (4): 440–451. doi:10.1016/S1470-2045(15)00560-4.
• Porceddu, Sandro V (April 2016). "A TNM classification for HPV+ oropharyngeal cancer". The Lancet Oncology (Editorial). 17 (4): 403–404. doi:10.1016/S1470-2045(15)00611-7. {{cite journal}}: Invalid |ref=harv (help)

Treatment

• Adelstein, David J.; Li, Yi; Adams, George L.; Wagner, Henry; Kish, Julie A.; Ensley, John F.; Schuller, David E.; Forastiere, Arlene A. (January 2003). "An Intergroup Phase III Comparison of Standard Radiation Therapy and Two Schedules of Concurrent Chemoradiotherapy in Patients With Unresectable Squamous Cell Head and Neck Cancer". Journal of Clinical Oncology. 21 (1): 92–98. doi:10.1200/JCO.2003.01.008.
• Adelstein, David J.; Ridge, John A.; Brizel, David M.; Holsinger, F. Christopher; Haughey, Bruce H.; O'Sullivan, Brian; Genden, Eric M.; Beitler, Jonathan J.; Weinstein, Gregory S.; Quon, Harry; Chepeha, Douglas B.; Ferris, Robert L.; Weber, Randal S.; Movsas, Benjamin; Waldron, John; Lowe, Val; Ramsey, Scott; Manola, Judith; Yueh, Bevan; Carey, Thomas E.; Bekelman, Justin E.; Konski, Andre A.; Moore, Eric; Forastiere, Arlene; Schuller, David E.; Lynn, Jean; Ullmann, Claudio Dansky (December 2012). "Transoral resection of pharyngeal cancer: Summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia". Head & Neck. 34 (12): 1681–1703. doi:10.1002/hed.23136.
• Al-Mamgani, Abrahim; van Rooij, Peter; Verduijn, Gerda M.; Mehilal, Robert; Kerrebijn, Jeroen D.; Levendag, Peter C. (February 2013). "The impact of treatment modality and radiation technique on outcomes and toxicity of patients with locally advanced oropharyngeal cancer". The Laryngoscope. 123 (2): 386–393. doi:10.1002/lary.23699.
• de Almeida, John R.; Byrd, James K.; Wu, Rebecca; Stucken, Chaz L.; Duvvuri, Uma; Goldstein, David P.; Miles, Brett A.; Teng, Marita S.; Gupta, Vishal; Genden, Eric M. (September 2014). "A systematic review of transoral robotic surgery and radiotherapy for early oropharynx cancer: A systematic review". The Laryngoscope. 124 (9): 2096–2102. doi:10.1002/lary.24712.
• An, Yi; Holsinger, F. Christopher; Husain, Zain A. (20 December 2016). "De-intensification of adjuvant therapy in human papillomavirus-associated oropharyngeal cancer". Cancers of the Head & Neck (Review). 1 (1). doi:10.1186/s41199-016-0016-7. {{cite journal}}: Invalid |ref=harv (help)CS1 maint: unflagged free DOI (link)
• Bachaud, Jean-Marc; Cohen-Jonathan, Elizabeth; Alzieu, Claude; David, Jean-Marc; Serrano, Elie; Daly-Schveitzer, Nicolas (December 1996). "Combined postoperative radiotherapy and Weekly Cisplatin infusion for locally advanced head and neck carcinoma: Final report of a randomized trial". International Journal of Radiation Oncology*Biology*Physics. 36 (5): 999–1004. doi:10.1016/S0360-3016(96)00430-0.
• Beitler, Jonathan J.; Zhang, Qiang; Fu, Karen K.; Trotti, Andy; Spencer, Sharon A.; Jones, Christopher U.; Garden, Adam S.; Shenouda, George; Harris, Jonathan; Ang, Kian K. (May 2014). "Final Results of Local-Regional Control and Late Toxicity of RTOG 9003: A Randomized Trial of Altered Fractionation Radiation for Locally Advanced Head and Neck Cancer". International Journal of Radiation Oncology Biology Physics. 89 (1): 13–20. doi:10.1016/j.ijrobp.2013.12.027.
• Bernier, Jacques; Domenge, Christian; Ozsahin, Mahmut; Matuszewska, Katarzyna; Lef?bvre, Jean-Louis; Greiner, Richard H.; Giralt, Jordi; Maingon, Philippe; Rolland, Fr?d?ric; Bolla, Michel; Cognetti, Francesco; Bourhis, Jean; Kirkpatrick, Anne; van Glabbeke, Martine (6 May 2004). "Postoperative Irradiation with or without Concomitant Chemotherapy for Locally Advanced Head and Neck Cancer". New England Journal of Medicine. 350 (19): 1945–1952. doi:10.1056/NEJMoa032641.
• Bernier, Jacques; Cooper, Jay S.; Pajak, T. F.; van Glabbeke, M.; Bourhis, J.; Forastiere, Arlene; Ozsahin, Esat Mahmut; Jacobs, John R.; Jassem, J.; Ang, Kie-Kian; Lefèbvre, J. L. (October 2005). "Defining risk levels in locally advanced head and neck cancers: A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501)". Head & Neck. 27 (10): 843–850. doi:10.1002/hed.20279.
• Blanchard, Pierre; Baujat, Bertrand; Holostenco, Victoria; Bourredjem, Abderrahmane; Baey, Charlotte; Bourhis, Jean; Pignon, Jean-Pierre (July 2011). "Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): A comprehensive analysis by tumour site". Radiotherapy and Oncology. 100 (1): 33–40. doi:10.1016/j.radonc.2011.05.036.
• Bonner, James A; Harari, Paul M; Giralt, Jordi; Cohen, Roger B; Jones, Christopher U; Sur, Ranjan K; Raben, David; Baselga, Jose; Spencer, Sharon A; Zhu, Junming; Youssoufian, Hagop; Rowinsky, Eric K; Ang, K Kian (January 2010). "Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival". The Lancet Oncology. 11 (1): 21–28. doi:10.1016/S1470-2045(09)70311-0.
• Bourhis, Jean; Overgaard, Jens; Audry, Hélène; Ang, Kian K; Saunders, Michele; Bernier, Jacques; Horiot, Jean-Claude; Le Maître, Aurélie; Pajak, Thomas F; Poulsen, Michael G; O'Sullivan, Brian; Dobrowsky, Werner; Hliniak, Andrzej; Skladowski, Krzysztof; Hay, John H; Pinto, Luiz HJ; Fallai, Carlo; Fu, Karen K; Sylvester, Richard; Pignon, Jean-Pierre (September 2006). "Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis". The Lancet. 368 (9538): 843–854. doi:10.1016/S0140-6736(06)69121-6.
• Brockstein, Bruce E.; Vokes, Everett E. (February 2011). "Head and neck cancer in 2010: Maximizing survival and minimizing toxicity". Nature Reviews Clinical Oncology. 8 (2): 72–74. doi:10.1038/nrclinonc.2010.226. {{cite journal}}: Invalid |ref=harv (help)
• Calais, Gilles; Bardet, Etienne; Sire, Christian; Alfonsi, Marc; Bourhis, Jean; Rhein, Béatrix; Tortochaux, Jacques; Man, Yooye Tao Kong; Auvray, Hugues; Garaud, Pascal (January 2004). "Radiotherapy with concomitant weekly docetaxel for Stages III/IV oropharynx carcinoma. Results of the 98-02 GORTEC Phase II trial". International Journal of Radiation Oncology Biology Physics. 58 (1): 161–166. doi:10.1016/S0360-3016(03)01370-1.
• Canis, Martin; Martin, Alexios; Kron, Martina; Konstantinou, Alexandra; Ihler, Friedrich; Wolff, Hendrik A.; Matthias, Christoph; Steiner, Wolfgang (29 December 2012). "Results of transoral laser microsurgery in 102 patients with squamous cell carcinoma of the tonsil". European Archives of Oto-Rhino-Laryngology. 270 (8): 2299–2306. doi:10.1007/s00405-012-2335-6.
• Chen, Allen M.; Daly, Megan E.; Luu, Quang; Donald, Paul J.; Farwell, D. Gregory (March 2015). "Comparison of functional outcomes and quality of life between transoral surgery and definitive chemoradiotherapy for oropharyngeal cancer". Head & Neck. 37 (3): 381–385. doi:10.1002/hed.23610.
• Chia, Stanley H.; Gross, Neil D.; Richmon, Jeremy D. (December 2013). "Surgeon Experience and Complications with Transoral Robotic Surgery (TORS)". Otolaryngology-Head and Neck Surgery. 149 (6): 885–892. doi:10.1177/0194599813503446.
• Choby, Garret W.; Kim, Jeehong; Ling, Diane C.; Abberbock, Shira; Mandal, Rajarsi; Kim, Seungwon; Ferris, Robert L.; Duvvuri, Umamaheswar (1 June 2015). "Transoral Robotic Surgery Alone for Oropharyngeal Cancer". JAMA Otolaryngology–Head & Neck Surgery. 141 (6): 499. doi:10.1001/jamaoto.2015.0347.
• Cohen, Marc A.; Weinstein, Gregory S.; O'Malley, Bert W.; Feldman, Michael; Quon, Harry (April 2011). "Transoral robotic surgery and human papillomavirus status: Oncologic results". Head & Neck. 33 (4): 573–580. doi:10.1002/hed.21500.
• Cooper, Jay S.; Pajak, Thomas F.; Forastiere, Arlene A.; Jacobs, John; Campbell, Bruce H.; Saxman, Scott B.; Kish, Julie A.; Kim, Harold E.; Cmelak, Anthony J.; Rotman, Marvin; Machtay, Mitchell; Ensley, John F.; Chao, K.S. Clifford; Schultz, Christopher J.; Lee, Nancy; Fu, Karen K. (6 May 2004). "Postoperative Concurrent Radiotherapy and Chemotherapy for High-Risk Squamous-Cell Carcinoma of the Head and Neck". New England Journal of Medicine. 350 (19): 1937–1944. doi:10.1056/NEJMoa032646.
• Cooper, Jay S.; Zhang, Qiang; Pajak, Thomas F.; Forastiere, Arlene A.; Jacobs, John; Saxman, Scott B.; Kish, Julie A.; Kim, Harold E.; Cmelak, Anthony J.; Rotman, Marvin; Lustig, Robert; Ensley, John F.; Thorstad, Wade; Schultz, Christopher J.; Yom, Sue S.; Ang, K. Kian (December 2012). "Long-term Follow-up of the RTOG 9501/Intergroup Phase III Trial: Postoperative Concurrent Radiation Therapy and Chemotherapy in High-Risk Squamous Cell Carcinoma of the Head and Neck". International Journal of Radiation Oncology Biology Physics. 84 (5): 1198–1205. doi:10.1016/j.ijrobp.2012.05.008.
• Corry, June; Peters, Lester J.; Rischin, Danny (10 January 2015). "Impact of Center Size and Experience on Outcomes in Head and Neck Cancer". Journal of Clinical Oncology. 33 (2): 138–140. doi:10.1200/JCO.2014.58.2239.
• Dziegielewski, Peter T.; Teknos, Theodoros N.; Durmus, Kasim; Old, Matthew; Agrawal, Amit; Kakarala, Kiran; Marcinow, Anna; Ozer, Enver (1 November 2013). "Transoral Robotic Surgery for Oropharyngeal Cancer". JAMA Otolaryngology Head & Neck Surgery. 139 (11): 1099. doi:10.1001/jamaoto.2013.2747.
• Dowthwaite, Samuel A.; Franklin, Jason H.; Palma, David A.; Fung, Kevin; Yoo, John; Nichols, Anthony C. (2012). "The Role of Transoral Robotic Surgery in the Management of Oropharyngeal Cancer: A Review of the Literature". ISRN Oncology. 2012: 1–14. doi:10.5402/2012/945162.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Eriksen, J. G.; Lassen, P.; Overgaard, J. (2010). "Do all patients with head and neck cancer benefit from radiotherapy and concurrent cetuximab?". The Lancet Oncology. 11 (4): 312–313. doi:10.1016/S1470-2045(10)70035-8. PMID 20359659.
• Fakhry, C.; Westra, W.; Li, S.; Cmelak, A.; Ridge, J.; Pinto, H.; Forastiere, A.; Gillison, M. (Feb 2008). "Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial". Journal of the National Cancer Institute. 100 (4): 261–269. doi:10.1093/jnci/djn011. ISSN 0027-8874. PMID 18270337.
• Fakhry, Carole; Zhang, Qiang; Nguyen-Tan, Phuc Felix; Rosenthal, David; El-Naggar, Adel; Garden, Adam S.; Soulieres, Denis; Trotti, Andy; Avizonis, Vilija; Ridge, John Andrew; Harris, Jonathan; Le, Quynh-Thu; Gillison, Maura (20 October 2014). "Human Papillomavirus and Overall Survival After Progression of Oropharyngeal Squamous Cell Carcinoma". Journal of Clinical Oncology. 32 (30): 3365–3373. doi:10.1200/JCO.2014.55.1937.
• Fundakowski, Christopher E.; Lango, Miriam (11 July 2016). "Considerations in surgical versus non-surgical management of HPV positive oropharyngeal cancer". Cancers of the Head & Neck (Review). 1 (1). doi:10.1186/s41199-016-0007-8. {{cite journal}}: Invalid |ref=harv (help)CS1 maint: unflagged free DOI (link)
• Genden, Eric M.; Kotz, Tamar; Tong, Charles C. L.; Smith, Claris; Sikora, Andrew G.; Teng, Marita S.; Packer, Stuart H.; Lawson, William L.; Kao, Johnny (August 2011). "Transoral robotic resection and reconstruction for head and neck cancer". The Laryngoscope. 121 (8): 1668–1674. doi:10.1002/lary.21845.
• Givens, Daniel J.; Karnell, Lucy Hynds; Gupta, Anjali K.; Clamon, Gerald H.; Pagedar, Nitin A.; Chang, Kristi E.; Van Daele, Douglas J.; Funk, Gerry F. (21 December 2009). "Adverse Events Associated With Concurrent Chemoradiation Therapy in Patients With Head and Neck Cancer". Archives of Otolaryngology–Head & Neck Surgery. 135 (12): 1209. doi:10.1001/archoto.2009.174.
• Haughey, Bruce H.; Hinni, Michael L.; Salassa, John R.; Hayden, Richard E.; Grant, David G.; Rich, Jason T.; Milov, Simon; Lewis, James S.; Krishna, Murli (December 2011). "Transoral laser microsurgery as primary treatment for advanced-stage oropharyngeal cancer: A united states multicenter study". Head & Neck. 33 (12): 1683–1694. doi:10.1002/hed.21669.
• Hunter, Klaudia U.; Schipper, Matthew; Feng, Felix Y.; Lyden, Teresa; Haxer, Mark; Murdoch-Kinch, Carol-Anne; Cornwall, Benjamin; Lee, Connie S.Y.; Chepeha, Douglas B.; Eisbruch, Avraham (March 2013). "Toxicities Affecting Quality of Life After Chemo-IMRT of Oropharyngeal Cancer: Prospective Study of Patient-Reported, Observer-Rated, and Objective Outcomes". International Journal of Radiation Oncology Biology Physics. 85 (4): 935–940. doi:10.1016/j.ijrobp.2012.08.030.
• Kramer, Simon; Gelber, Richard D.; Snow, James B.; Marcial, Victor A.; Lowry, Louis D.; Davis, Lawrence W.; Chandler, Richard (September 1987). "Combined radiation therapy and surgery in the management of advanced head and neck cancer: Final report of study 73?03 of the radiation therapy oncology group". Head & Neck Surgery. 10 (1): 19–30. doi:10.1002/hed.2890100105.
• Machtay, Mitchell; Moughan, Jennifer; Trotti, Andrew; Garden, Adam S.; Weber, Randal S.; Cooper, Jay S.; Forastiere, Arlene; Ang, K. Kian (20 July 2008). "Factors Associated With Severe Late Toxicity After Concurrent Chemoradiation for Locally Advanced Head and Neck Cancer: An RTOG Analysis". Journal of Clinical Oncology. 26 (21): 3582–3589. doi:10.1200/JCO.2007.14.8841.
• Marur, Shanthi; Li, Shuli; Cmelak, Anthony J.; Gillison, Maura L.; Zhao, Weiqiang J.; Ferris, Robert L.; Westra, William H.; Gilbert, Jill; Bauman, Julie E.; Wagner, Lynne I.; Trevarthen, David R.; Balkrishna, Jahagirdar; Murphy, Barbara A.; Agrawal, Nishant; Colevas, A. Dimitrios; Chung, Christine H.; Burtness, Barbara (10 February 2017). "E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx— ECOG-ACRIN Cancer Research Group". Journal of Clinical Oncology. 35 (5): 490–497. doi:10.1200/JCO.2016.68.3300.
• Maxwell, Jessica H.; Mehta, Vikas; Wang, Hong; Cunningham, Diana; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas; Ferris, Robert L. (July 2014). "Quality of life in head and neck cancer patients: Impact of HPV and primary treatment modality". The Laryngoscope. 124 (7): 1592–1597. doi:10.1002/lary.24508.
• Mehanna, H (2017). "Update on De-intensification and Intensification Studies in HPV". Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer. 206: 251–256. doi:10.1007/978-3-319-43580-0_20. PMID 27699545. {{cite journal}}: Invalid |ref=harv (help) excerpt here
• Moore, Eric J.; Olsen, Steven M.; Laborde, Rebecca R.; García, Joaquín J.; Walsh, Francis J.; Price, Daniel L.; Janus, Jeffrey R.; Kasperbauer, Jan L.; Olsen, Kerry D. (March 2012). "Long-term Functional and Oncologic Results of Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma". Mayo Clinic Proceedings. 87 (3): 219–225. doi:10.1016/j.mayocp.2011.10.007.
• Moore, Eric J.; Hinni, Michael L. (April 2013). "Critical Review: Transoral Laser Microsurgery and Robotic-Assisted Surgery for Oropharynx Cancer Including Human Papillomavirus Related Cancer". International Journal of Radiation Oncology Biology Physics. 85 (5): 1163–1167. doi:10.1016/j.ijrobp.2012.08.03.
• More, Yogesh I.; Tsue, Terance T.; Girod, Douglas A.; Harbison, John; Sykes, Kevin J.; Williams, Carson; Shnayder, Yelizaveta (1 January 2013). "Functional Swallowing Outcomes Following Transoral Robotic Surgery vs Primary Chemoradiotherapy in Patients With Advanced-Stage Oropharynx and Supraglottis Cancers". JAMA Otolaryngology Head & Neck Surgery. 139 (1): 43. doi:10.1001/jamaoto.2013.1074.
• Nguyen-Tan, Phuc Felix; Zhang, Qiang; Ang, K. Kian; Weber, Randal S.; Rosenthal, David I.; Soulieres, Denis; Kim, Harold; Silverman, Craig; Raben, Adam; Galloway, Thomas J.; Fortin, André; Gore, Elizabeth; Westra, William H.; Chung, Christine H.; Jordan, Richard C.; Gillison, Maura L.; List, Marcie; Le, Quynh-Thu (December 2014). "Randomized Phase III Trial to Test Accelerated Versus Standard Fractionation in Combination With Concurrent Cisplatin for Head and Neck Carcinomas in the Radiation Therapy Oncology Group 0129 Trial: Long-Term Report of Efficacy and Toxicity". Journal of Clinical Oncology. 32 (34): 3858–3867. doi:10.1200/JCO.2014.55.3925.
• Parsons, James T.; Mendenhall, William M.; Stringer, Scott P.; Amdur, Robert J.; Hinerman, Russell W.; Villaret, Douglas B.; Moore-Higgs, Giselle J.; Greene, Bruce D.; Speer, Tod W.; Cassisi, Nicholas J.; Million, Rodney R. (1 June 2002). "Squamous cell carcinoma of the oropharynx: Surgery, radiation therapy, or both". Cancer. 94 (11): 2967–2980. doi:10.1002/cncr.10567.
• Pignon, Jean-Pierre; le Maître, Aurélie; Bourhis, Jean (October 2007). "Meta-Analyses of Chemotherapy in Head and Neck Cancer (MACH-NC): An Update". International Journal of Radiation Oncology Biology Physics. 69 (2): S112–S114. doi:10.1016/j.ijrobp.2007.04.088.
• Pollei, Taylor R.; Hinni, Michael L.; Moore, Eric J.; Hayden, Richard E.; Olsen, Kerry D.; Casler, John D.; Walter, Logan C. (1 November 2013). "Analysis of Postoperative Bleeding and Risk Factors in Transoral Surgery of the Oropharynx". JAMA Otolaryngology Head & Neck Surgery. 139 (11): 1212. doi:10.1001/jamaoto.2013.5097. PMID 24113922.
• Posner, M. R.; Lorch, J. H.; Goloubeva, O.; Tan, M.; Schumaker, L. M.; Sarlis, N. J.; Haddad, R. I.; Cullen, K. J. (May 2011). "Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial". Annals of Oncology. 22 (5): 1071–1077. doi:10.1093/annonc/mdr006.
• Quon, Harry; Richmon, Jeremy D. (August 2012). "Treatment Deintensification Strategies for HPV-Associated Head and Neck Carcinomas". Otolaryngologic Clinics of North America. 45 (4): 845–861. doi:10.1016/j.otc.2012.04.007. {{cite journal}}: Invalid |ref=harv (help)
• Rich, Jason T.; Milov, Simon; Lewis, James S.; Thorstad, Wade L.; Adkins, Douglas R.; Haughey, Bruce H. (September 2009). "Transoral laser microsurgery (TLM) ?? adjuvant therapy for advanced stage oropharyngeal cancer". The Laryngoscope. 119 (9): 1709–1719. doi:10.1002/lary.20552. PMC 3877921. PMID 19572271.
• Rinaldi, V; Pagani, D; Torretta, S; Pignataro, L (26 September 2013). "Transoral robotic surgery in the management of head and neck tumours". Ecancermedicalscience. 7: 359. doi:10.3332/ecancer.2013.359. PMID 24073017.
• Sinclair, CF; McColloch, NL; Carroll, WR; Rosenthal, EL; Desmond, RA; Magnuson, JS (November 2011). "Patient-perceived and objective functional outcomes following transoral robotic surgery for early oropharyngeal carcinoma". Archives of Otolaryngology Head & Neck Surgery. 137 (11): 1112–6. doi:10.1001/archoto.2011.172. PMID 22106235.
• Spanos, William C.; Nowicki, Paul; Lee, Dong Wook; Hoover, Andrew; Hostager, Bruce; Gupta, Anjali; Anderson, Mary E.; Lee, John H. (1 November 2009). "Immune Response During Therapy With Cisplatin or Radiation for Human Papillomavirus–Related Head and Neck Cancer". Archives of Otolaryngology–Head & Neck Surgery. 135 (11): 1137. doi:10.1001/archoto.2009.159.
• Steiner, Wolfgang; Fierek, Oliver; Ambrosch, Petra; Hommerich, Christian P.; Kron, Martina (1 January 2003). "Transoral Laser Microsurgery for Squamous Cell Carcinoma of the Base of the Tongue". Archives of Otolaryngology-Head & Neck Surgery. 129 (1): 36. doi:10.1001/archotol.129.1.36.
• Vikram, Bhadrasain; Strong, Elliot W.; Shah, Jatin P.; Spiro, Ronald (January 1984). "Failure at the primary site following multimodality treatment in advanced head and neck cancer". Head & Neck Surgery. 6 (3): 720–723. doi:10.1002/hed.2890060303.
• Walvekar, Rohan R.; Li, Ryan J.; Gooding, William E.; Gibson, Michael K.; Heron, Dwight; Johnson, Jonas T.; Ferris, Robert L. (December 2008). "Role of Surgery in Limited (T1-2, N0-1) Cancers of the Oropharynx". The Laryngoscope. 118 (12): 2129–2134. doi:10.1097/MLG.0b013e3181857950.
• Weinstein, Gregory S.; O'Malley, Bert W.; Magnuson, J. Scott; Carroll, William R.; Olsen, Kerry D.; Daio, Lixia; Moore, Eric J.; Holsinger, F. Christopher (August 2012). "Transoral robotic surgery: A multicenter study to assess feasibility, safety, and surgical margins". The Laryngoscope. 122 (8): 1701–1707. doi:10.1002/lary.23294.
• White, Hilliary N.; Moore, Eric J.; Rosenthal, Eben L.; Carroll, William R.; Olsen, Kerry D.; Desmond, Reneé A.; Magnuson, J. Scott (20 December 2010). "Transoral Robotic-Assisted Surgery for Head and Neck Squamous Cell Carcinoma". Archives of Otolaryngology–Head & Neck Surgery. 136 (12): 1248. doi:10.1001/archoto.2010.216.
• Woody, Neil M.; Koyfman, Shlomo A.; Xia, Ping; Yu, Naichang; Shang, Qingyang; Adelstein, David J.; Scharpf, Joseph; Burkey, Brian; Nwizu, Tobenna; Saxton, Jerold; Greskovich, John F. (February 2016). "Regional control is preserved after dose de-escalated radiotherapy to involved lymph nodes in HPV positive oropharyngeal cancer". Oral Oncology. 53: 91–96. doi:10.1016/j.oraloncology.2015.11.004.

Prognosis

• Ang, K. K.; Harris, J.; Wheeler, R.; Weber, R.; Rosenthal, D. I.; Nguyen-Tân, P. F.; Westra, W. H.; Chung, C. H.; Jordan, R. C.; Lu, C.; Kim, H.; Axelrod, R.; Silverman, C. C.; Redmond, K. P.; Gillison, M. L. (2010). "Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer". New England Journal of Medicine. 363 (1): 24–35. doi:10.1056/NEJMoa0912217. PMC 2943767. PMID 20530316. {{cite journal}}: Cite has empty unknown parameter: |1= (help)
• Chernock, R. D.; El-mofty, S. K.; Thorstad, W. L.; Parvin, C. A.; Lewis, J. S. (2009). "HPV-Related Nonkeratinizing Squamous Cell Carcinoma of the Oropharynx: Utility of Microscopic Features in Predicting Patient Outcome". Head and Neck Pathology. 3 (3): 186–194. doi:10.1007/s12105-009-0126-1. PMC 2811624. PMID 20596971.
• Fischer, C. A.; Kampmann, M.; Zlobec, I.; Green, E.; Tornillo, L.; Lugli, A.; Wolfensberger, M.; Terracciano, L. M. (27 April 2010). "p16 expression in oropharyngeal cancer: its impact on staging and prognosis compared with the conventional clinical staging parameters". Annals of Oncology. 21 (10): 1961–1966. doi:10.1093/annonc/mdq210.
• Gillison, Maura L.; Zhang, Qiang; Jordan, Richard; Xiao, Weihong; Westra, William H.; Trotti, Andy; Spencer, Sharon; Harris, Jonathan; Chung, Christine H.; Ang, K. Kian (10 June 2012). "Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal Cancer". Journal of Clinical Oncology. 30 (17): 2102–2111. doi:10.1200/JCO.2011.38.4099.
• Hafkamp, Harriët C.; Manni, J.J.; Haesevoets, A.; Voogd, A.C.; Schepers, M.; Bot, F.J.; Hopman, A.H.N.; Ramaekers, F.C.S.; Speel, Ernst-Jan M. (15 June 2008). "Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas". International Journal of Cancer. 122 (12): 2656–2664. doi:10.1002/ijc.23458.
• de Jong, M. C.; Pramana, J.; Knegjens, J. L.; Balm, A. J. M.; Van Den Brekel, M. W. M.; Hauptmann, M.; Begg, A. C.; Rasch, C. R. N. (24 March 2010). "HPV and high-risk gene expression profiles predict response to chemoradiotherapy in head and neck cancer, independent of clinical factors". Radiotherapy and Oncologyissn=1879-0887. 95 (3): 365–370. doi:10.1016/j.radonc.2010.02.001. PMID 20346528.
• Lewis, James S; Carpenter, Danielle H; Thorstad, Wade L; Zhang, Qin; Haughey, Bruce H (24 June 2011). "Extracapsular extension is a poor predictor of disease recurrence in surgically treated oropharyngeal squamous cell carcinoma". Modern Pathology. 24 (11): 1413–1420. doi:10.1038/modpathol.2011.105.
• Licitra, Lisa; Perrone, Federica; Bossi, Paolo; Suardi, Simona; Mariani, Luigi; Artusi, Raffaella; Oggionni, Maria; Rossini, Chiara; Cantù, Giulio; Squadrelli, Massimo; Quattrone, Pasquale; Locati, Laura D.; Bergamini, Cristiana; Olmi, Patrizia; Pierotti, Marco A.; Pilotti, Silvana (20 December 2006). "High-Risk Human Papillomavirus Affects Prognosis in Patients With Surgically Treated Oropharyngeal Squamous Cell Carcinoma". Journal of Clinical Oncology. 24 (36): 5630–5636. doi:10.1200/JCO.2005.04.6136.
• Lowy, D.; Munger, K. (2010). "Prognostic Implications of HPV in Oropharyngeal Cancer". The New England Journal of Medicine. 363 (1): 82–84. doi:10.1056/NEJMe1003607. PMID 20530315. {{cite journal}}: Invalid |ref=harv (help)
• Maxwell, J. H.; Kumar, B.; Feng, F. Y.; Worden, F. P.; Lee, J. S.; Eisbruch, A.; Wolf, G. T.; Prince, M. E.; Moyer, J. S.; Teknos, T. N.; Chepeha, D. B.; McHugh, J. B.; Urba, S. G.; Stoerker, J.; Walline, H. M.; Kurnit, D. M.; Cordell, K. G.; Davis, S. J.; Ward, P. D.; Bradford, C. R.; Carey, T. E. (9 February 2010). "Tobacco Use in Human Papillomavirus-Positive Advanced Oropharynx Cancer Patients Related to Increased Risk of Distant Metastases and Tumor Recurrence". Clinical Cancer Research. 16 (4): 1226–1235. doi:10.1158/1078-0432.CCR-09-2350. PMC 2822887. PMID 20145161. {{cite journal}}: Cite has empty unknown parameter: |1= (help)
• Maxwell, Jessica H.; Ferris, Robert L.; Gooding, William; Cunningham, Diana; Mehta, Vikas; Kim, Seungwon; Myers, Eugene N.; Johnson, Jonas; Chiosea, Simion (September 2013). "Extracapsular spread in head and neck carcinoma: Impact of site and human papillomavirus status". Cancer. 119 (18): 3302–3308. doi:10.1002/cncr.28169.
• Ragin, Camille C. R.; Taioli, Emanuela (15 October 2007). "Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: Review and meta-analysis". International Journal of Cancer. 121 (8): 1813–1820. doi:10.1002/ijc.22851. {{cite journal}}: Invalid |ref=harv (help)
• Rischin, Danny; Young, Richard J.; Fisher, Richard; Fox, Stephen B.; Le, Quynh-Thu; Peters, Lester J.; Solomon, Ben; Choi, Jimin; O'Sullivan, Brian; Kenny, Lizbeth M.; McArthur, Grant A. (20 September 2010). "Prognostic Significance of p16INK4A and Human Papillomavirus in Patients With Oropharyngeal Cancer Treated on TROG 02.02 Phase III Trial". Journal of Clinical Oncology. 28 (27): 4142–4148. doi:10.1200/JCO.2010.29.2904.

Epidemiology

• Anantharaman, Devasena; Muller, David C; Lagiou, Pagona; Ahrens, Wolfgang; Holc?tov?, Ivana; Merletti, Franco; Kj?rheim, Kristina; Polesel, Jerry; Simonato, Lorenzo; Canova, Cristina; Castellsague, Xavier; Macfarlane, Tatiana V; Znaor, Ariana; Thomson, Peter; Robinson, Max; Conway, David I; Healy, Claire M; Tj?nneland, Anne; Westin, Ulla; Ekstr?m, Johanna; Chang-Claude, Jenny; Kaaks, Rudolf; Overvad, Kim; Drogan, Dagmar; Hallmans, G?ran; Laurell, G?ran; Bueno-de-Mesquita, HB; Peeters, Petra H; Agudo, Antonio; Larra?aga, Nerea; Travis, Ruth C; Palli, Domenico; Barricarte, Aurelio; Trichopoulou, Antonia; George, Saitakis; Trichopoulos, Dimitrios; Quir?s, J Ram?n; Grioni, Sara; Sacerdote, Carlotta; Navarro, Carmen; S?nchez, Mar?a-Jos?; Tumino, Rosario; Severi, Gianluca; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Francoise; Panico, Salvatore; Weiderpass, Elisabete; Lund, Eiliv; Gram, Inger T; Riboli, Elio; Pawlita, Michael; Waterboer, Tim; Kreimer, Aim?e R; Johansson, Mattias; Brennan, Paul (June 2016). "Combined effects of smoking and HPV16 in oropharyngeal cancer". International Journal of Epidemiology. 45 (3): 752–761. doi:10.1093/ije/dyw069.
• Chaturvedi, A.; Engels, E.; Anderson, W.; Gillison, M. (Feb 2008). "Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States" (PDF). Journal of Clinical Oncology. 26 (4): 612–619. doi:10.1200/JCO.2007.14.1713. ISSN 0732-183X. PMID 18235120.
• Chaturvedi, Anil K.; Engels, Eric A.; Pfeiffer, Ruth M.; Hernandez, Brenda Y.; Xiao, Weihong; Kim, Esther; Jiang, Bo; Goodman, Marc T.; Sibug-Saber, Maria; Cozen, Wendy; Liu, Lihua; Lynch, Charles F.; Wentzensen, Nicolas; Jordan, Richard C.; Altekruse, Sean; Anderson, William F.; Rosenberg, Philip S.; Gillison, Maura L. (10 November 2011). "Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States". Journal of Clinical Oncology. 29 (32): 4294–4301. doi:10.1200/JCO.2011.36.4596. PMC 3221528. PMID 21969503.
• Chaturvedi, Anil K.; Anderson, William F.; Lortet-Tieulent, Joannie; Curado, Maria Paula; Ferlay, Jacques; Franceschi, Silvia; Rosenberg, Philip S.; Bray, Freddie; Gillison, Maura L. (20 December 2013). "Worldwide Trends in Incidence Rates for Oral Cavity and Oropharyngeal Cancers". Journal of Clinical Oncology. 31 (36): 4550–4559. doi:10.1200/JCO.2013.50.3870.
• Chenevert, J; Chiosea, S (January 2012). "Incidence of human papillomavirus in oropharyngeal squamous cell carcinomas: now and 50 years ago". Human Pathology. 43 (1): 17–22. doi:10.1016/j.humpath.2011.03.009. PMID 21777945. {{cite journal}}: Invalid |ref=harv (help)
• Cook, M.; Dawsey, S.; Freedman, N.; Inskip, P.; Wichner, S.; Quraishi, S.; Devesa, S.; McGlynn, K. (2009). "Sex disparities in cancer incidence by time period and age". Cancer Epidemiology, Biomarkers & Prevention. 18 (4): 1174–1182. doi:10.1158/1055-9965.EPI-08-1118. PMC 2793271. PMID 19293308.
• Dayyani, Farshid; Etzel, Carol J; Liu, Mei; Ho, Chung-Han; Lippman, Scott M; Tsao, Anne S (2010). "Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC)". Head & Neck Oncology. 2 (1): 15. doi:10.1186/1758-3284-2-15.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• D'Souza, G.; Kreimer, A.; Viscidi, R.; Pawlita, M.; Fakhry, C.; Koch, W.; Westra, W.; Gillison, M. (May 2007). "Case-control study of human papillomavirus and oropharyngeal cancer". The New England Journal of Medicine. 356 (19): 1944–1956. doi:10.1056/NEJMoa065497. ISSN 0028-4793. PMID 17494927.
• Ernster, J.; Sciotto, C.; O'Brien, M.; Finch, J.; Robinson, L.; Willson, T.; Mathews, M. (Dec 2007). "Rising incidence of oropharyngeal cancer and the role of oncogenic human papilloma virus". The Laryngoscope. 117 (12): 2115–2128. doi:10.1097/MLG.0b013e31813e5fbb. ISSN 0023-852X. PMID 17891052.
• Hammarstedt, L.; Lindquist, D.; Dahlstrand, H.; Romanitan, M.; Dahlgren, L.; Joneberg, J.; Creson, N.; Lindholm, J.; Ye, W.; Dalianis, T.; Munck-Wikland, E. (Dec 2006). "Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer". International Journal of Cancer. Journal International Du Cancer. 119 (11): 2620–2623. doi:10.1002/ijc.22177. ISSN 0020-7136. PMC 2817092. PMID 16991119.
• Heck, Julia E; Berthiller, Julien; Vaccarella, Salvatore; Winn, Deborah M; Smith, Elaine M; Shan'gina, Oxana; Schwartz, Stephen M; Purdue, Mark P; Pilarska, Agnieszka; Eluf-Neto, Jose; Menezes, Ana; McClean, Michael D; Matos, Elena; Koifman, Sergio; Kelsey, Karl T; Herrero, Rolando; Hayes, Richard B; Franceschi, Silvia; Wünsch-Filho, Victor; Fernández, Leticia; Daudt, Alexander W; Curado, Maria Paula; Chen, Chu; Castellsagué, Xavier; Ferro, Gilles; Brennan, Paul; Boffetta, Paolo; Hashibe, Mia (February 2010). "Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium". International Journal of Epidemiology. 39 (1): 166–181. doi:10.1093/ije/dyp350. PMID 20022926.
• Hemminki, K; Dong, C; Frisch, M (December 2000). "Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands". European Journal of Cancer Prevention. 9 (6): 433–437. doi:10.1097/00008469-200012000-00010. PMID 11201683.
• Hong, Angela M.; Grulich, Andrew E.; Jones, Deanna; Lee, C. Soon; Garland, Suzanne M.; Dobbins, Timothy A.; Clark, Jonathan R.; Harnett, Gerald B.; Milross, Christopher G.; O’Brien, Christopher J.; Rose, Barbara R. (April 2010). "Squamous cell carcinoma of the oropharynx in Australian males induced by human papillomavirus vaccine targets". Vaccine. 28 (19): 3269–3272. doi:10.1016/j.vaccine.2010.02.098. PMID 20226244.
• Jemal, A.; Siegel, R.; Ward, E.; Hao, Y.; Xu, J.; Murray, T.; Thun, M. J. (28 January 2008). "Cancer Statistics, 2008". CA: A Cancer Journal for Clinicians. 58 (2): 71–96. doi:10.3322/CA.2007.0010. {{cite journal}}: Check |journal= value (help)
• Marur, S.; D'souza, G.; Westra, W. H.; Forastiere, A. A. (2010). "HPV-associated head and neck cancer: a virus-related cancer epidemic". The Lancet Oncology. 11 (8): 781–789. doi:10.1016/S1470-2045(10)70017-6. PMID 20451455.
• Näsman, A.; Attner, P.; Hammarstedt, L.; Du, J.; Eriksson, M.; Giraud, G.; Ahrlund-Richter, S.; Marklund, L.; Romanitan, M.; Lindquist, D.; Ramqvist, T. R.; Lindholm, J.; Sparén, P. R.; Ye, W.; Dahlstrand, H.; Munck-Wikland, E.; Dalianis, T. (July 2009). "Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma?". International Journal of Cancer. Journal International Du Cancer. 125 (2): 362–366. doi:10.1002/ijc.24339. PMID 19330833.
• Siegel, Rebecca; Naishadham, Deepa; Jemal, Ahmedin (January 2013). "Cancer statistics, 2013". CA: A Cancer Journal for Clinicians. 63 (1): 11–30. doi:10.3322/caac.21166.
• Siegel, Rebecca L.; Miller, Kimberly D.; Jemal, Ahmedin (January 2017). "Cancer statistics, 2017". CA: A Cancer Journal for Clinicians. 67 (1): 7–30. doi:10.3322/caac.21387.

Books, chapters and theses

• Cardesa, Antonio; Slootweg, Pieter J.; Gale, Nina; Franchi, Alessandro, eds. (2017). Pathology of the Head and Neck (2nd ed.). Springer. ISBN 978-3-662-49672-5. {{cite book}}: Cite has empty unknown parameter: |1= (help)
• Chaturvedi, Anil; Gillison, Maura L. Human Papillomavirus and Head and Neck Cancer. pp. 87–116. ISBN 978-1-4419-1471-2., in Olshan (2010)
• Hammarstedt, Lalle (25 April 2008), Tonsillar Cancer - Incidence, Prevalence of HPV and Survival (PhD thesis), Stockholm: Department of Clinical Neuroscience, Karolinska Institutet, ISBN 978-91-7357-587-4, retrieved 3 June 2017
• Hayat, M. A., ed. (2010). Methods of Cancer Diagnosis, Therapy, and Prognosis: Volume 7 - General Overviews, Head and Neck Cancer and Thyroid Cancer. Springer Science & Business Media. ISBN 978-90-481-3186-0. {{cite book}}: Invalid |ref=harv (help)
• Munck-Wikland, Eva; Hammarstedt, Lalle; Dahlstrand, Hanna. Role of Human Papillomavirus in Tonsillar Cancer. pp. 271–283. {{cite book}}: Cite has empty unknown parameter: |1= (help), in Hayat (2010) (additional extract here)
• Myers, Jeffrey N.; Sturgis, Erich M., eds. (2013). Oral Cavity and Oropharyngeal Cancer, An Issue of Otolaryngologic Clinics, E-Book. Elsevier Health Sciences. ISBN 978-0-323-18632-2. {{cite book}}: Invalid |ref=harv (help)
• Olshan, Andrew F., ed. (2010). Epidemiology, Pathogenesis, and Prevention of Head and Neck Cancer. Springer Science & Business Media. ISBN 978-1-4419-1471-2. {{cite book}}: Invalid |ref=harv (help)
• IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. vol 90: Human Papillomaviruses. Lyon: International Agency for Research on Cancer. 2007.
• Marur, S.; D'souza, G.; Westra, W. H.; Forastiere, A. A. (2010). "HPV-associated head and neck cancer: a virus-related cancer epidemic". The Lancet Oncology. 11 (8): 781–789. doi:10.1016/S1470-2045(10)70017-6. PMID 20451455.

Websites

• "Head and Neck Cancers" (PDF). NCCN Guidelines 2.2017. National Comprehensive Cancer Network. 2017. Retrieved 29 May 2017.
• Hunt, Jennifer L (21 March 2010). "Molecular Assessment of HPV in Patients with Head and Neck Tumors" (PDF). Association for Molecular Pathology. United States and Canadian Academy of Pathology. Archived from the original (PDF) on 16 July 2011. Retrieved 30 May 2017. {{cite web}}: Invalid |ref=harv (help)
• "Cancer of the Oral Cavity and Pharynx by Subsite" (PDF). SEER Cancer Statistics Review 1975-2007. Surveillance, Epidemiology, and End Results (SEER) Program. 15 April 2010. Retrieved 3 June 2017. {{cite web}}: Cite has empty unknown parameter: |1= (help)

Clinical trials

• "Post Operative Adjuvant Therapy De-intensification Trial for Human Papillomavirus-related, p16+ Oropharynx Cancer (ADEPT)". clinicaltrials.gov. National Library of Medicine. 2 February 2017. {{cite web}}: |access-date= requires |url= (help); Missing or empty |url= (help)
• "RTOG 9003. A Phase III Randomized Study to Compare Twice Daily Hyperfractionation, Accelerated Hyperfractionation with a Split and Accelerated Fractionation with Concomitant Boost to Standard Fractionation Radiotherapy for Squamous Cell Carcinomas of the Head and Neck". RTOG. 6 November 2013. Retrieved 1 June 2017.
• "Phase III Intergroup Trial of Surgery Followed by (1) Radiotherapy vs. (2) Radiochemotherapy for Resectable High Risk Squamous Cell Carcinoma of the Head and Neck". RTOG. 6 November 2013. Retrieved 15 June 2017.
• "RTOG 0129. A Phase III Trial of Concurrent Radiation and Chemotherapy (Followed by Surgery for Residual Primary/N2-3 Nodal Disease) for Advanced Head and Neck Carcinomas". RTOG. 23 July 2014. Retrieved 1 June 2017.

External links

• Is Oral Sex Safe? (Television production). England: BBC Three. 10 January 2011.