Salvage surgery of hypopharyngeal cancer as a second malignancy post radiotherapy and the possibility of digestive track reconstruction – study of three cases and the literature review

Patients with head and neck cancers have an increased risk of second malignant neoplasm occurrence (25% in long-term follow-up, 4% yearly). Most patients with a primary tumor can be treated with organ-preserving strategies including radiotherapy (RT) or chemoradiotherapy (CRT). Very often after radical surgical excision there are indications for adjuvant radiotherapy. However, if recurrence or second malignancy will develop after definitive primary RT, there are limitation to use therapeutic dose of radiation again for the same area. Salvage surgery is regarded as the only curative option in those cases. In our study we analysed 3 patients, who presented with head and neck second cancer in the area of hypopharynx, within 10-25 years after primary radiotherapy due to oropharyngeal and laryngeal cancer. A total pharyngectomy with larynx preservation and bilateral neck dissection were performed in the first case and the radial forearm free flap (RFFF) was used for reconstruction of the pharynx. Second patient, due to perilaryngeal invasion in radiological images, underwent total pharyngolaryngectomy with selective bilateral cervical lymph nodes dissection and digestive track was restored also with RFFF. The third patient had previously undergone laryngectomy and after total pharyngectomy the free autologous jejunal flap (FAJF) was used for reconstruction. The main goal of reconstruction after salvage surgery due to hypopharyngeal cancer is to reconstruct the digestive tract. The other important aspect is to optimize the anatomy for voice rehabilitation and swallowing. Unfortunately, radiation and chemotherapy impair wound healing, which indicates increased risk of postoperative complications and makes salvage surgery results unpredictable.

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Long-term incidence of venous thromboembolism (VTE) among survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.10562 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 10562-10562

Author(s):

Arin L Madenci ◽

Brent Weil ◽

Qi Liu ◽

Todd M. Gibson ◽

Yutaka Yasui ◽

...

Keyword(s):

High Risk ◽

Childhood Cancer ◽

Chronic Conditions ◽

Malignant Neoplasm ◽

Cancer Recurrence ◽

Care Providers ◽

Second Malignant Neoplasm ◽

Increased Risk ◽

Survivors Of Childhood Cancer

10562 Background: This study aimed to estimate the incidence of late-occurring VTE among survivors of childhood cancer, and to identify associated demographic and clinical factors that define high-risk subgroups for potential screening and prevention. Methods: Using data from CCSS, a multi-institutional, longitudinal cohort of 5-year survivors of childhood cancer (diagnosed 1970-1999) and their siblings, the primary endpoint of self-reported late VTE (occurring ≥5 years after diagnosis) was estimated using multivariable piecewise exponential models adjusted for age, sex, and race. Generalized estimating equations accounted for potential within-family correlation where applicable. Results: Among 23,601 survivors and 5051 siblings, the incidence of VTE was 1.15 and 0.48 events per 1000 person-years, respectively. For survivors, median age at last follow-up was 28.6 years (range 5.6-58.3) and median follow-up time from diagnosis was 21.2 years (range 5.0-39.3). The adjusted rate ratio (RR) for survivors compared to siblings was 2.2 (95% confidence interval [CI] = 1.7-2.8, P< 0.01). Among survivors, risk factors for VTE included BMI≥30kg/m2 (ref. BMI 18.5-24.5; RR = 1.5, CI = 1.2-2.0, P< 0.01), increasing number of severe or life-threatening (i.e. CTCAE grades 3 or 4) non-VTE chronic conditions (ref. 0 conditions; 1-2 conditions: RR = 2.5, CI = 2.0-3.1, P< 0.01 ; ≥3 conditions: RR = 3.5, CI = 2.5-4.9, P< 0.01), and cancer recurrence or second malignant neoplasm (RR = 3.5, CI = 2.7-4.6, P< 0.01). Incidence of late VTE was associated with increased subsequent mortality, independent of non-VTE chronic conditions (RR 2.2, 95% CI = 1.7-2.8, P< 0.01). Conclusions: Survivors of childhood cancer remain at increased risk for VTE across their lifespan. While typically not causal, late VTE was associated with subsequent mortality. Care providers should be aware of this increased risk and consider interventions that target modifiable co-morbidities such as obesity. Surveillance and education should be directed toward high-risk survivors.

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Reirradiation After Surgery and Microvascular Reconstruction

Otolaryngology ◽

10.1016/j.otohns.2008.05.501 ◽

2008 ◽

Vol 139 (2_suppl) ◽

pp. P93-P93

Author(s):

Jeffrey D. Suh ◽

Brian Paul Kim ◽

Elliot Abemayor ◽

Joel A Sercarz ◽

Vishad Nabili ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Free Flap ◽

Salvage Surgery ◽

Late Complications ◽

Microvascular Reconstruction ◽

Increased Risk ◽

Cord Injury ◽

Recurrent Head

Problem To evaluate the outcome and complications of reirradiation of recurrent head and neck cancer after salvage surgery and microvascular reconstruction. Methods Retrospective Study. Twelve patients underwent salvage surgery with microvascular reconstruction for recurrent or new primary head and neck cancer in a previously irradiated field. Median prior RT dose was 63.0 Gy (range 30.0–72.8). Patients then underwent postoperative reirradiation, receiving a median total cumulative radiation dose of 115.0 Gy. Results Three patients (25%) experienced acute complications (<3 months) during reirradiation that resolved with conservative care. Four patients (33%) developed grade 3 or 4 late reirradiation complications (>3 months). There were no incidences of free flap failure. No patients suffered brain necrosis, spinal cord injury, or carotid rupture. The incidence of soft tissue necrosis and osteoradionecrosis was 8%. There were no treatment-related mortalities. Six patients (50%) are alive without evidence of recurrent disease a median of 40 months after reirradiation (range 4–64 months). Conclusion Free flap reconstruction followed by reirradiation is not associated with an increased risk of perioperative, acute, or late complications. Microvascular free flaps allow for maximal resection and reliable reconstruction of previously irradiated cancers before high dose reirradiation, and may reduce the incidence of severe late complications and treatment related mortality. Significance Reirradiation for recurrent head and neck squamous cell carcinoma remains controversial. However, increasing evidence has demonstrated improved survival and locoregional control with reirradiation at the cost of potentially severe or sometimes fatal radiation toxicity. We hypothesize that using well-vascularized tissue and bone at the time of salvage surgery can reduce the incidence of reirradiation complications. This would allow patients at high risk for recurrence to more safely receive a second course of radiation therapy. To our knowledge this is the first report of the effects of microvascular reconstruction on complications and outcomes of patients undergoing salvage surgery and external beam reirradiation.

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Cancer screening in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.18_suppl.cra6501 ◽

2009 ◽

Vol 27 (18_suppl) ◽

pp. CRA6501-CRA6501 ◽

Cited By ~ 1

Author(s):

P. C. Nathan ◽

K. K. Ness ◽

M. M. Hudson ◽

M. Mahoney ◽

J. S. Ford ◽

...

Keyword(s):

High Risk ◽

Cancer Survivors ◽

Childhood Cancer ◽

Pap Smear ◽

Malignant Neoplasm ◽

Childhood Cancer Survivors ◽

Cancer Center ◽

Second Malignant Neoplasm ◽

Increased Risk ◽

Population Controls

CRA6501 Background: Childhood cancer survivors may develop a second malignant neoplasm (SMN) and require surveillance to detect new cancers. Methods: We surveyed survivors and siblings from the CCSS, a cohort study of patients who have survived ≥5 years after a diagnosis of childhood cancer from 1970–86. We assessed compliance with the American Cancer Society's (ACS) guidelines for surveillance mammography, colonoscopy and PAP smears, and compared them to a matched population comparison group drawn from the 2003 National Health Interview Survey. Further, we examined compliance with the Children's Oncology Group (COG) guidelines for more frequent colonoscopy, mammography and skin exams in survivors at high risk for cancers of the colon (≥30 Gy pelvic, abdominal or spinal radiation), breast (≥ 20 Gy breast radiation in females) or skin (any radiation). Proportions screened were compared between groups with adjusted generalized estimating equations or log-binomial regression models. Results: There were 8318 survivors (50.6% male, mean age at interview 31.2 ± 7.3 years), 2661 siblings and 8318 population controls. 141/829 (17.6%), 592/855 (70.4%) and 3362/3690 (92.6%) eligible survivors reported a colonoscopy, mammogram, or PAP smear per ACS guidelines. Survivors were less likely than siblings (odds ratio [OR] 0.30; 95% confidence interval [CI] 0.18–0.49) and population controls (OR 0.63; CI 0.50–0.80) to have a colonoscopy, and less likely than siblings to have a PAP smear (risk ratio [RR] 0.98; CI 0.97–0.99). However, they were more likely than siblings (RR 1.14; CI 1.03–1.27) and population controls (RR 1.05; CI 1.01–1.10) to have a mammogram. Among survivors at increased risk for a SMN, only 92/809 (11.4%) reported a colonoscopy within the COG recommended 5-year period, 164/537 (30.5%) reported a mammogram within a 1-year period and 1288/4833 (26.7%) reported a skin exam. Care at a cancer center was associated with mammography (RR 1.91; 95% CI 1.02–1.27) and skin exam (RR 1.55; 95% CI 1.22–196) in high-risk patients. Conclusions: Childhood cancer survivors are not screened adequately for SMNs. Surveillance is very poor amongst those at highest risk for colon, breast, or skin cancer. Survivors and their physicians need education about the importance of surveillance. No significant financial relationships to disclose.

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Risk of second malignant neoplasm and mortality in patients with rheumatoid arthritis treated with biological DMARDs: a Danish population-based cohort study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-212086 ◽

2017 ◽

Vol 77 (4) ◽

pp. 510-514 ◽

Cited By ~ 10

Author(s):

Lene Dreyer ◽

René L Cordtz ◽

Inger Marie J Hansen ◽

Lars Erik Kristensen ◽

Merete L Hetland ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cancer Diagnosis ◽

Malignant Neoplasm ◽

Population Based ◽

Cancer Site ◽

Primary Cancer ◽

Second Malignant Neoplasm ◽

Increased Risk ◽

Before And After ◽

History Of

ObjectiveTo study the risk of a second malignant neoplasm (SMN) and mortality in patients with rheumatoid arthritis (RA) with a history of a primary cancer diagnosis and treated with biological disease-modifying antirheumatic drugs (bDMARD).MethodsAmong patients with RA (n=15 286) registered in the DANBIO Register during 2000–2011, 1678 had a primary cancer according to the Danish Cancer Registry. HRs for SMN and death were calculated.ResultsDuring follow-up there were 279 patients with RA contributing person-years to the bDMARDs use before their primary cancer diagnosis, 220 to the only after, 92 to the both before and after, while 1203 patients with RA contributed to the non-use strata. Ever use of bDMARDs was associated with a HR of 1.11 (95% CI 0.74 to 1.67) for developing a SMN compared with non-use (cancer site adjusted). The HR for death associated with bDMARD use before the primary cancer diagnosis was increased 1.53 (95% CI 1.13 to 2.09). After further adjustment for extent of the primary cancer, the HR for death was 1.20 (95% CI 0.88 to 1.63) for bDMARDs use before cancer, 1.36 (95% CI 0.78 to 2.39) for bDMARD use only after cancer and 1.22 (95% CI 0.70 to 2.13) for use both before and after the cancer.ConclusionsAmong patients with RA with a history of cancer, treatment with bDMARDs was not associated with increased risk of SMN. No clear conclusion can be drawn regarding mortality in bDMARD-treated patients with RA.

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Salvage Reconstructive Surgery During Nivolumab Therapy for a Patient With Hypopharyngeal Cancer

Clinical Medicine Insights Case Reports ◽

10.1177/1179547620908854 ◽

2020 ◽

Vol 13 ◽

pp. 117954762090885

Author(s):

Nayuta Tsushima ◽

Takeshi Shinozaki ◽

Takao Fujisawa ◽

Toshifumi Tomioka ◽

Wataru Okano ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Reconstructive Surgery ◽

Salvage Surgery ◽

Single Agent ◽

Oral Intake ◽

Hypopharyngeal Cancer ◽

Primary Disease ◽

Neck Disease

Objectives: Nivolumab, a fully IgG4-programmed death-1 inhibitor antibody, led to improved overall survival compared with single-agent therapy in patients with platinum-refractory recurrent head and neck cancers. In general, nivolumab is used in inoperable patients. To the best of our knowledge, there have been no reports of salvage surgery during nivolumab therapy for patients with head and neck cancer. We report the case of a woman treated with salvage reconstructive surgery during nivolumab therapy. Method: Case report and literature review. Results: The patient underwent nivolumab therapy for recurrent primary and neck disease after induction chemotherapy, followed by concurrent chemoradiation therapy. The neck disease shrunk, whereas the primary disease temporarily shrunk but later progressed again. Recurrent primary disease led to a narrowing of her airway, and she required airway management. We performed total pharyngolaryngectomy with free jejunal reconstruction, and her quality of life improved. The surgery was performed without complications and the postoperative course was uneventful. She was discharged postoperative day 18 with oral intake function and a safer airway. Conclusion: As far as we know, this is the first report of salvage surgery during nivolumab therapy for patients with head and neck cancer. The salvage reconstructive surgery in this case proceeded uneventfully.

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Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

Blood ◽

10.1182/blood-2008-11-187880 ◽

2009 ◽

Vol 113 (24) ◽

pp. 6077-6084 ◽

Cited By ~ 97

Author(s):

Kjeld Schmiegelow ◽

Ibrahim Al-Modhwahi ◽

Mette Klarskov Andersen ◽

Mikael Behrendtz ◽

Erik Forestier ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Maintenance Therapy ◽

Lymphoblastic Leukemia ◽

Cumulative Risk ◽

Malignant Neoplasm ◽

Tpmt Activity ◽

Second Malignant Neoplasm ◽

Childhood All ◽

Monosomy 7 ◽

Increased Risk

Abstract Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16 acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P = .07) were related to increased risk of SMN. Thiopurine methyltransferase (TPMT) methylates 6MP and its metabolites, and thus reduces cellular levels of cytotoxic 6-thioguanine nucleotides. Of 524 patients who had erythrocyte TPMT activity measured, the median TPMT activity in 9 patients developing an SMN was significantly lower than in the 515 that did not develop an SMN (median, 12.1 vs 18.1 IU/mL; P = .02). Among 427 TPMT wild-type patients for whom the 6MP dose was registered, those who developed SMN received higher average 6MP doses than the remaining patients (69.7 vs 60.4 mg/m2; P = .03). This study indicates that the duration and intensity of 6MP/MTX maintenance therapy of childhood ALL may influence the risk of SMNs in childhood ALL.

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Increased Risk of Suicide among Cancer Survivors Who Developed a Second Malignant Neoplasm

Computational Intelligence and Neuroscience ◽

10.1155/2022/2066133 ◽

2022 ◽

Vol 2022 ◽

pp. 1-11

Author(s):

Huazhen Yang ◽

Yuanyuan Qu ◽

Yanan Shang ◽

Chengshi Wang ◽

Junren Wang ◽

...

Keyword(s):

General Population ◽

Cancer Survivors ◽

Cancer Diagnosis ◽

Malignant Neoplasm ◽

Sociodemographic Factors ◽

Population Based ◽

Second Malignant Neoplasm ◽

Suicide Death ◽

Increased Risk ◽

Standardized Mortality Ratios

Background. Cancer diagnosis entails substantial psychological distress and is associated with dramatically increased risks of suicidal behaviors. However, little is known about the suicide risk among cancer survivors who developed a second malignant neoplasm (SMN). Methods. Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study involving 7,824,709 patients with first malignant neoplasm (FMN). We measured the hazard ratios (HRs) of suicide death after receiving a SMN diagnosis using Cox proportional hazard models, as compared with patients with FMN. The comparison with the US population was achieved by calculating standardized mortality ratios (SMRs). Results. Totally 685,727 FMN patients received a diagnosis of SMN during follow-up, and we in total identified 10,930 and 937 suicide deaths among FMN and SMN patients, respectively. The HR of suicide deaths was 1.23 (95% confidence interval (CI), 1.14–1.31) after a SMN diagnosis, compared with FMN patients, after adjusting for sociodemographic factors, tumor characteristics, and cancer treatment. As compared with the general population, while both SMN and FMN patients suffered an increased risk of suicide deaths, the excess risk was higher among SMN patients than FMN patients (age-, sex-, and calendar-year-adjusted SMR 1.65 (95% CI 1.54–1.75) vs. 1.29 (95% CI 1.26–1.31); P difference < 0.0001 ). Notably, across different time periods, we observed the greatest risk elevation during the first 3 months after a cancer diagnosis. Conclusions. Compared with either patients with FMN or the general population, cancer survivors who received a SMN diagnosis were at increased risk of suicide death. The risk elevation was most prominent soon after the cancer diagnosis, highlighting the necessity of providing timely psychological support to cancer survivors with a SMN.

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Bilateral testicular germ cell tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.392 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 392-392

Author(s):

Stephanie A. Curreri ◽

Sarah C. Markt ◽

Rowan Miller ◽

Elizabeth O'Donnell ◽

Brandon David Bernard ◽

...

Keyword(s):

Testicular Cancer ◽

Germ Cell ◽

Cause Of Death ◽

Germ Cell Tumors ◽

Malignant Neoplasm ◽

Patient Characteristics ◽

Second Malignant Neoplasm ◽

Testicular Germ Cell ◽

Risk Of Death ◽

Increased Risk

392 Background: Germ cell tumors (GCTs), both seminomatous and non-seminomatous, account for greater than 90% of testicular cancers. While bilateral testicular GCTs are rare, the incidence of bilateral tumors has increased over time. Methods: 668 cases of bilateral and 38,593 cases of unilateral testicular GCTs were reported between 1973 and 2011 by the SEER database. Patient characteristics and tumor features were analyzed. Results: The incidence of bilateral GCTs among men with testicular GCTs was 1.7% (668 of 39,261 total cases). Among the 668 men with bilateral GCTs, 53% (n=353) of second GCTs occurred within three years after the first cancer. 29% (n=196) of bilateral tumors occurred synchronously. Among patients with bilateral GCTs, 378 first GCTs and 466 second GCTs were seminomatous. 43% of bilateral cases were concordant seminomatous GCTs, 16% were concordant non-seminomas, and 41% were discordant histologies. 68% of unilateral GCTs, 70% of first GCTs, and 82% of second GCTs were staged as Localized disease. Testicular cancer was the cause of death for 4% (n=1,630) of men with a unilateral GCT and 1% (n=8) of men with bilateral GCTs. A second malignant neoplasm (SMN) was the cause of death for 2% (n=736) of men with a unilateral GCT and 2% (n=16) of men with bilateral GCTs. Conclusions: Among men with bilateral testicular GCTs, 59% had concordant histological diagnoses between their first and second tumor. Most (53%) second cancers among men with bilateral tumors occurred within three years after diagnosis of first cancers. Men who experience bilateral testicular GCTs do not appear to have an increased risk of death due to testicular cancer or a subsequent non-germ cell malignant neoplasm compared to men with a unilateral testicular GCT. [Table: see text]

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Risk of Selected Subsequent Carcinomas in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.7235 ◽

2006 ◽

Vol 24 (3) ◽

pp. 476-483 ◽

Cited By ~ 179

Author(s):

Mylène Bassal ◽

Ann C. Mertens ◽

Leslie Taylor ◽

Joseph P. Neglia ◽

Brian S. Greffe ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Childhood Cancer ◽

Head And Neck ◽

Cancer Survivor ◽

Malignant Neoplasm ◽

Increased Risk ◽

Childhood Cancer Survivor Study ◽

Survivors Of Childhood Cancer

Purpose To determine the risk of subsequent carcinomas other than breast, thyroid, and skin, and to identify factors that influence the risk among survivors of childhood cancer. Patients and Methods Subsequent malignant neoplasm history was determined in 13,136 participants (surviving ≥ 5 years postmalignancy, diagnosed from 1970 to 1986 at age < 21 years) of the Childhood Cancer Survivor Study to calculate standardized incidence ratios (SIRs), using Surveillance, Epidemiology, and End Results data. Results In 71 individuals, 71 carcinomas were diagnosed at a median age of 27 years and a median elapsed time of 15 years in the genitourinary system (35%), head and neck area (32%), gastrointestinal tract (23%), and other sites (10%). Fifty-nine patients (83%) had received radiotherapy, and 42 (59%) developed a second malignant neoplasm in a previous radiotherapy field. Risk was significantly elevated following all childhood diagnoses except CNS neoplasms, and was highest following neuroblastoma (SIR = 24.2) and soft tissue sarcoma (SIR = 6.2). Survivors of neuroblastoma had a 329-fold increased risk of renal cell carcinomas; survivors of Hodgkin's lymphoma had a 4.5-fold increased risk of gastrointestinal carcinomas. Significantly elevated risk of head and neck carcinoma occurred in survivors of soft tissue sarcoma (SIR = 22.6), neuroblastoma (SIR = 20.9), and leukemia (SIR = 20.9). Conclusion Young survivors of childhood cancers are at increased risk of developing subsequent carcinomas typical of later adulthood, underscoring the importance of long-term follow-up and risk-based screening. Follow-up of the cohort is ongoing to determine lifetime risk and delineate individual characteristics that contribute to risk.

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Family History of Head and Neck Cancers

Cancers ◽

10.3390/cancers13164115 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4115

Author(s):

Xinjun Li ◽

Anni I. Koskinen ◽

Otto Hemminki ◽

Asta Försti ◽

Jan Sundquist ◽

...

Keyword(s):

High Risk ◽

Head And Neck ◽

Oropharyngeal Cancer ◽

Hpv Vaccination ◽

Nasopharyngeal Cancer ◽

Hpv Infection ◽

Hypopharyngeal Cancer ◽

Head And Neck Cancers ◽

Swedish Population ◽

Increased Risk

Background: Head and neck cancers (HNCs) encompass a heterogeneous group of cancers between the mouth and larynx. Familial clustering in HNCs has been described, but how it influences individual sites and to which extent known risk factors, such as human papilloma virus (HPV) infection, may contribute is not well established. Patients/methods: We employed standardized incidence ratios (SIRs) to estimate familial risks for HNC with same (concordant) and different (discordant) cancers among first-degree relatives using data from the Swedish Cancer Registry from 1958 to 2018. Results: Incidence for male and female oropharyngeal cancer increased close to four-fold in the past 39 years. Familial HNC was found in 3.4% of the study population, with an overall familial SIR of 1.78. Patients with concordant nasopharyngeal cancer showed a high risk of 23.97, followed by hypopharyngeal cancer (5.43). The husbands of wives with cervical cancer had an increased risk of oropharyngeal cancer. Discussion/Conclusion: Nasopharyngeal cancers lacked associations with lifestyle or HPV associated cancers, suggesting a role for germline genetics, which was also true for the high-risk families of three HNC patients. In the Swedish population with low smoking levels, HPV is becoming a dominant risk factor, emphasizing the need for sexual hygiene and HPV vaccination.

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