The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) has increased, and staging and optimal therapeutic approaches are challenging. A questionnaire survey was conducted to investigate the controversial treatment policy of stage T2 OPC according to the N category and determine the opinions of multidisciplinary experts in Korea.
Five OPC scenarios were developed by the Subcommittee on Oropharyngeal Treatment Guidelines of the Korean Society for Head and Neck Oncology and distributed to experts of multidisciplinary treatment hospitals.
Sixty-five experts from 45 institutions responded. For the HPV-positive T2N0M0 scenario, 67.7% of respondents selected surgery followed by definitive concurrent chemoradiotherapy (CCRT) or radiotherapy alone. For the T2N1M0 HPV-positive scenario, there was a notable difference in the selection of primary treatment by expert specialty; 53.9% of respondents selected surgery and 39.8% selected definitive CCRT as the primary treatment. For the T2N3M0 advanced HPV-positive scenario, 50.0% of respondents selected CCRT and 33.3% considered induction chemotherapy (IC) as the primary treatment. CCRT and IC were significantly more frequently selected for the HPV-related OPC cases (p=0.010). The interdepartmental variability showed that the head and neck surgeons and medical oncologists favored surgery, whereas the radiation oncologists preferably selected definitive CCRT (p < 0.001).
In this study, surgery was preferred for lymph node-negative OPC, and as lymph node metastasis progressed, CCRT tended to be preferred, and IC was administered. Clinical practice patterns by stage and HPV status showed differences according to expert specialty. Multidisciplinary consensus guidelines will be essential in the future.
The incidence of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) has increased around the world and has recently been staged separately [
To achieve an increased cure rate and lower complication rate with these good prognostic diseases, proper multidisciplinary treatment guidelines are mandatory [
The purpose of this study was to investigate the current nationwide treatment policies for OPC and suggest opinions for preparing multidisciplinary consensus guidelines that are evidence-based and appropriately fit to the Korean medical environment. Since the amount is vast to investigate the treatment policy for entire OPC, this study focused on finding out the initial treatment decision for OPC, which may have disagreements among interdisciplinary. Therefore, the scenario was limited to T2 category and treatment policy according to the N category was reflected.
The survey was developed by the Subcommittee on Oropharyngeal Treatment Guidelines of the Korean Society for Head and Neck Oncology (KSHNO). The questionnaires asked about treatment policies for five scenarios depending on the stage or status of HPV infection. All cases were staged according to the American Joint Committee on Cancer (AJCC) 8th edition for both clinical and pathologic staging. Questionnaires were sent to all board-certified expert members of KSHNO who practice multimodal treatment of head and neck cancer in Korea. The questionnaire was sent via e-mail twice from July to August 2019, and the results were collected and analyzed in October 2019. The images and clinical summaries for the five scenarios are shown in
A 61-year-old male patient without underlying disease visited with a sore throat. His performance status was Eastern Cooperative Oncology Group performance status (ECOG PS) 1, and he had a 10 pack-per-year (PPY) smoking history. After imaging study and biopsy, he was diagnosed with HPV(+) squamous cell carcinoma (SCC) with clinical stage T2N0M0, and there was no base of tongue invasion. The choice of the first treatment method for this patient was investigated.
A 52-year-old female patient, ECOG PS 1, was a non-smoker without underlying disease admitted for a 3.3-cm-sized mass in the right tonsil and multiple metastatic lymph nodes on the right level II–III, and there was no tongue base invasion. The final diagnosis was HPV(+) SCC, and the clinical stage was T2N1M0. The questionnaire asked about the first treatment modality of choice.
A 49-year-old female non-smoker and ECOG PS 1 without underlying disease visited for a sore throat and a palpable huge mass on the left neck. A 4-cm-sized mass without base of tongue invasion in the left tonsil and metastatic lymph nodes in the ipsilateral upper, middle, and lower internal jugular chain were observed. A biopsy confirmed HPV(+) SCC, and the clinical stage was T2N3M0. The questionnaire asked about the first treatment for this patient.
A 69-year-old man, ECOG PS 1, with a 30-PPY smoking history visited the hospital with a sore throat. On magnetic resonance imaging, a mass of 2.2 cm, with the longest diameter in the left tonsil, was suspicious of tongue base invasion, and a 1.7-cm-sized lymph node metastasis was seen at ipsilateral cervical level II. He was diagnosed with HPV(−) SCC, and the clinical stage was T2N1M0. The first treatment for his cancer was queried.
A 59-year-old male 20-PPY smoker visited the hospital for a sore throat. His pretreatment performance status was ECOG PS 1. HPV(−) SCC was diagnosed as clinical stage T2N2bM0 with a 2-cm-sized mass without tongue base invasion in the right tonsil and several lymph node metastases at ipsilateral cervical level II–III. The first treatment for his cancer was queried.
The questionnaires were sent to experts in treating head and neck tumors from 86 institutions in Korea with more than 300 beds, and responses were received from individuals or multidisciplinary teams representing the institutions. Multidisciplinary team gathered together in each department to derive the consensus opinion and submit the answer. The content of the returned data was anonymized and analyzed. In the questionnaire, the professional medical department, the period elapsed since board certification, the status of multidisciplinary consultation, and the method of surgery and radiation therapy in the institutions were surveyed. A chi-square test was performed to evaluate the relationship between treatment choice and each factor, such as HPV status, number of nodal metastases, department of experts, hospital beds, robotic surgery availability, and consultation meeting, and a p-value of less than 0.05 was considered statistically significant. Statistical analyses were performed using SPSS ver. 24 (IBM Corp., Armonk, NY).
A total of 59 individuals and six multidisciplinary teams from 45 institutions responded. The nationwide response rate was 52.3% (45/86 institutions). Thirteen out of 16 institutions with > 1,000 hospital beds (81.3%), 29 out of 60 institutions with 500–1,000 hospital beds (48.3%), and three out of 10 institutions with > 300 and ≤ 500 hospital beds (30%) replied to the survey, indicating a high response rate in institutions with a high number of hospital beds. The most responses were from experts from the department of radiation oncology (n=35, 53.8%), followed by head and neck surgeons (n=16, 24.6%), medical oncologists (n=8, 12.3%), and multidisciplinary teams (n=6, 9.2%).
The institutional surveys reported that 69.2% decided treatment modalities through regular head and neck conferences, 10.8% held meetings if necessary, and 18.5% decided through interdepartmental patient referrals. Robotic surgery was available in 67.7% of the institutions, and most respondents (93.8%), except for one, performed radiotherapy for head and neck tumors using the intensity-modulated radiotherapy technique. Data on the characteristics of the respondents are summarized in
A survey of the first treatment was conducted for both HPV(+) and HPV(−) OPC cases. The selection of the first treatment for each case is presented in
The results of the questionnaire for the primary treatment of HPV(−) OPC cases (cases 4 and 5) are shown in
For four scenarios, excluding case 1 without metastatic lymph nodes, a chi-square test was performed on the association between selection of treatment method and HPV status. CCRT and induction chemotherapy was more frequently chosen for the HPV(+) cases than for the HPV(−) cases, and the difference was significant (p=0.010; odds ratio, 9.276) (
The difference in the treatment options selected according to specialty was remarkable in each scenario. In
A significant difference was found according to the stage of the metastatic lymph node (
The number of hospital beds, the availability of robotic surgery, and the status of the consultation meeting were analyzed to determine trends by scenario (
The regimens and schedules of chemotherapeutic agents used in definitive CCRT were queried. Forty-four experts answered these questions, 41 of the respondents (93.2%) used cisplatin alone, and most of them used a weekly low-dose dosing schedule.
This study is meaningful as the first multidisciplinary survey study of OPC in Korea. The purpose of this study was to survey the current treatment patterns of OPC which may have disagreements interdisciplinary and suggest the need for evidence-based multidisciplinary consensus guidelines suitable for the Korean medical environment. We investigated initial treatment selection limited to T2, according to N category where various treatment strategies can be selected.
The mainstay treatment for OPC includes surgery and definitive chemoradiation or radiation alone. Recently, the de-intensification of treatment according to HPV status was proposed [
The results of this study showed differences in treatment policy according to HPV status and extent of nodal stage. Clinical studies on the treatment method for HPV(+) OPC are currently being actively conducted. In definitive CCRT, cetuximab was inferior in overall survival and progression-free survival (PFS) and had increased locoregional and distant failure rates compared to cisplatin in the phase III randomized clinical studies RTOG 1016 and De-ESCALaTE, in which cetuximab was substituted for cisplatin [
The preferred treatment method for each specialty showed different trends. Head and neck surgeons responded that advanced surgical techniques could be used and various surgical instruments have been developed, so surgical treatment was possible in OPC even at advanced stages [
The reason why the treatment choice is different is due to concerns about complications. Definitive CCRT for OPC is associated with increased toxicity, such as long-term dysphagia. A gastrostomy insertion rate of 24% at one year and 14% at 2 years after CCRT has been reported, and xerostomia is one of the leading causes associated with radiation-related complications [
The interesting point of this study is that induction chemotherapy was chosen as the first treatment in the cT2N3M0 HPV(+), even in the National Comprehensive Cancer Network (NCCN) guideline category 3 [
There were several limitations to this survey study. First, there were insufficient questions on surgical techniques for OPC. Although the questions on treatment method selection were surveyed by stage, opinions on surgical techniques were not objectively surveyed, as the differences were likely to vary depending on the surgical environment and equipment in the institution or the head and neck surgeon’s experience and perspectives. In addition, the treatment policy according to the N category was reflected, but questions according to the T category were insufficient. This is because, in general, surgery is recommended for T1, and induction chemotherapy or definitive CCRT is preferred for T3–4. Thus, the approaches are fairly consistent, so the scenario was limited to T2. However, there will be limitations in establishing an algorithm for the overall treatment of OPC.
The results of the expert questionnaire study reflected that the debate on the choice of treatment method was based on the perspective of the professional field and showed that this could be an obstacle to the preparation of clinical evidence. The 2019 American Society of Clinical Oncology and 2017 American Society for Radiation Oncology guidelines for OPC did not address the consensus of primary treatment [
In summary, the current survey of the clinical practice patterns of OPC in Korea showed that surgery was preferred for lymph node-negative OPC, and as lymph node metastasis progressed, CCRT tended to be preferred, and induction chemotherapy was also applied. A treatment consensus among multidisciplinary departments through active communication in academic societies like the KSHNO is needed to provide optimal therapy and reduce differences at each institution.
We observed different treatment policies between HPV-positive and HPV-negative patients in this survey. In addition, this survey will serve as the basis for creating a unified treatment guideline that takes into account differences in each hospital size or among experts. This will be the basis for treating OPC, considering both tumor control and complications, and establishing a treatment protocol that can be delivered at a reasonable social cost.
Supplementary materials are available at Cancer Research and Treatment website (
Conceived and designed the analysis: Choi KH, Song JH, Kim YS.
Collected the data: Choi KH, Kim YS, Kim JH, Jeong WJ, Nam IC, Kim JH, Ahn HK, Chun SH, Hong HJ, Joo YH, Eun YG, Moon SH, Lee J.
Contributed data or analysis tools: Choi KH, Song JH, Kim YS, Kim JH, Jeong WJ, Nam IC, Kim JH, Ahn HK, Chun SH, Hong HJ, Joo YH, Eun YG, Moon SH, Lee J.
Performed the analysis: Choi KH, Song JH, Kim YS, Kim JH, Jeong WJ, Nam IC, Kim JH, Ahn HK, Chun SH, Hong HJ, Joo YH, Eun YG, Moon SH, Lee J.
Wrote the paper: Choi KH, Kim YS.
Conflict of interest relevant to this article was not reported.
This work was supported by the Subcommittee on Oropharyngeal Treatment Guidelines of the KSHNO. We thank all of KSHNO respondents to this survey and experts treating head and neck tumors from 45 institutions who participated in this survey as follows: Asan Medical Center, Yonsei University Severance Hospital, Samsung Medical Center, Seoul National University Hospital, Gachon University Gil Medical Center, The Catholic University of Korea Seoul St. Mary’s Hospital, Chungnam National University Hospital, Bundang Seoul National University Hospital, Pusan National University Hospital, Ajou University Hospital, Jeonbuk National University Hospital, Korea University Anam Hospital, Korea University Guro Hospital, Kosin University Gopspel Hospital, Dong-A University Hospital, Keimyung University Dongsan Medical Center, Inha University Hospital, Soonchunhyang University Cheonan Hospital, Gyeongsang National University Hospital, Daegu Catholic University Medical Center, Ewha Womans University Medical Center, Hanyang University Seoul Hospital, Wonju Severance Christian Hospital, Chosun University Hospital, Kyung Hee University Hospital, The Catholic University of Korea Incheon St. Mary’s Hospital, Yonsei University Gangnam Severance Hospital, Inje University Busan Paik Hospital, Chungbuk National University Hospital, The Catholic University of Korea St. Vincent’s Hospital, Wonkwang University Hospital, The Catholic University of Korea Uijeongbu St. Mary’s Hospital, Chonnam National University Hwasun Hospital, Kangbuk Samsung Hospital, The Catholic University of Korea Daejeon St. Mary’s Hospital, Kyung Hee University Hospital at Gangdong, The Catholic University of Korea Bucheon St. Mary’s Hospital, Presbyterian Medical Center, National Cancer Center, Catholic Kwandong University International St. Mary’s Hospital, Merinol Hospital, Korea Cancer Center Hospital, The Catholic University of Korea Yeouido St. Mary’s Hospital, Hanyang University Guri Hospital, and The Catholic University of Korea Eunpyeong St. Mary’s Hospital.
Maximum intensity projection images of PET and clinical stage for five scenarios. AJCC, American Joint Committee on Cancer; HPV(+), human papillomavirus positive; HPV(−), human papillomavirus negative; PET, positron-emission tomography; PPY, pack-per-year.
Graphs for the proportion of responses according to the experts’ specialty in five scenarios (A–E, cases 1–5). The numbers in the stacked bar chart indicate each percentage of respondents who chose the treatment modality. CCRT, concurrent chemoradiotherapy; CTx, chemotherapy; HPV(+), human papillomavirus positive; HPV(−), human papillomavirus negative; RT, radiotherapy.
Graphs for the proportion of responses according to HPV status. CCRT, concurrent chemoradiotherapy; CTx, chemotherapy; HPV, human papillomavirus.
Graphs for the proportion of responses according to nodal stage. CCRT, concurrent chemoradiotherapy; CTx, chemotherapy.
Graphs for the proportion of responses according to hospital beds: T2N1M0 cases (A) and T2N2bM0 or T2N3M0 cases (B). CCRT, concurrent chemoradiotherapy; CTx, chemotherapy.
Characteristics of the respondents
Characteristic | No. (%) (n=65) |
---|---|
Otolaryngology | 16 (24.6) |
Radiation oncology | 35 (53.8) |
Medical oncology | 8 (12.3) |
Multidisciplinary team | 6 (9.2) |
< 5 | 6 (9.2) |
5–10 | 13 (20.0) |
11–20 | 22 (33.8) |
> 20 | 17 (26.2) |
N/A | 7 (10.8) |
> 1,000 | 21 (32.3) |
> 500 and ≤ 1,000 | 38 (58.5) |
> 300 and ≤ 500 | 5 (7.7) |
N/A | 1 (1.5) |
< 50 | 54 (83.1) |
50–100 | 8 (12.3) |
> 100 | 3 (4.6) |
Yes | 61 (93.8) |
No | 4 (6.2) |
Regular conference | 45 (69.2) |
Meeting if necessary | 7 (10.8) |
Interdepartmental referral | 12 (18.5) |
N/A | 1 (1.5) |
Available | 44 (67.7) |
Not used | 18 (27.7) |
N/A | 3 (4.6) |
Available | 61 (93.8) |
treatmentforhis Not used | 1 (1.5) |
N/A | 3 (4.6) |
IMRT, intensity-modulated radiotherapy; N/A, not available.
Factors affecting the choice of treatment modalities in node-positive cases
Characteristic | Surgery |
CCRT |
Induction chemotherapy |
p-value |
---|---|---|---|---|
Positive | 37 (38.5) | 49 (55.7) | 25 (64.1) | 0.010 |
Negative | 59 (61.5) | 39 (44.3) | 14 (35.9) | |
N1 | 65 (67.7) | 35 (39.8) | 7 (17.9) | < 0.001 |
N2–N3 | 31 (32.3) | 53 (60.2) | 32 (82.1) | |
Otolaryngology | 29 (30.2) | 11 (12.5) | 13 (33.3) | < 0.001 |
Radiation oncology | 37 (38.5) | 67 (76.1) | 16 (41.0) | |
Medical oncology | 17 (17.7) | 8 (9.1) | 6 (15.4) | |
Multidisciplinary team | 13 (13.5) | 2 (2.3) | 4 (10.3) | |
> 1,000 | 27 (28.1) | 35 (39.8) | 12 (30.8) | 0.149 |
> 500 and ≤ 1,000 | 57 (59.4) | 52 (59.1) | 24 (61.5) | |
> 300 and ≤ 500 | 8 (8.3) | 1 (1.1) | 3 (7.7) | |
N/A | 4 (4.2) | 0 ( | 0 ( | |
Available | 63 (65.6) | 59 (67.0) | 31 (79.5) | 0.280 |
Not used | 27 (28.1) | 28 (31.8) | 7 (17.9) | |
N/A | 6 (6.3) | 1 (1.1) | 1 (2.6) | |
Regular conference | 71 (74.0) | 61 (69.3) | 27 (69.2) | 0.781 |
Meeting if necessary | 8 (8.3) | 10 (11.4) | 5 (12.8) | |
Interdepartmental referral | 13 (13.5) | 17 (19.3) | 7 (17.9) | |
N/A | 4 (4.2) | 0 | 0 |
Values are presented as number (%). CCRT, concurrent chemoradiotherapy; HPV, human papillomavirus; N/A, not available.
Respondents who only selected one of treatment modalities were included.