Human Papillomavirus-related Oropharyngeal Cancer Research Articles

Hypofractionated radiation therapy alone for human papillomavirus-related oropharyngeal cancer.

To report a single-institutional experience with hypofractionated radiation therapy alone for human papillomavirus (HPV)-positive oropharyngeal cancer. A total of 101 consecutive patients were treated by radiation therapy alone using a regimen of 66 Gy in 30 fractions (60 patients) or 70 Gy in 33 fractions (41 patients) for newly diagnosed p16-positive squamous cell carcinoma of the oropharynx. Sixty-seven patients (67%) were never smokers. The 3-year actuarial rates of overall survival, local-regional control, and progression-free survival were 94%, 93%, and 89%, respectively. Among never-smokers, the 3-year rates of overall survival and local-regional control were 98% and 100%, respectively. The grade 3+ acute toxicity rate was 21%, with the most commonly observed side effects related to mucositis. Hypofractionated radiation alone resulted in excellent outcomes for patients with HPV-positive oropharyngeal cancer. A prospective clinical trial investigating this modality in the setting of de-escalation is currently underway.

Detection of HPV DNA in Saliva of Patients with HPV-Associated Oropharyngeal Cancer Treated with Radiotherapy.

To investigate the technical feasibility of RT-PCR and direct sequencing to quantify HPV DNA in the saliva of patients with Human-Papilloma-Virus related oropharyngeal cancer (HPV-OPC), the level of which is known to predict prognosis after treatment. Nine patients with locally advanced HPV-OPC treated with definitive radiotherapy with chemotherapy or cetuximab, or radiotherapy alone between April 2016 and September 2017, were enrolled, two of whom also received induction chemotherapy. Saliva was collected before (baseline), during (mid-RT) and after (post-RT) radiotherapy. HPV-16 DNAs (E6 and E7) in saliva were quantified by RT-PCR and sequencing, the latter using a custom cancer panel. Correlations between HPV DNA levels and clinical outcomes were assessed. Compared to the baseline, the relative cycle threshold (Ct) value of E6 and E7 reduced at the point of mid-RT in the majority of the patients (100% and 75% for E6 and E7, respectively). Similarly, the relative Ct value from the baseline to post-RT reduced in 86% and 100% of the patients for E6 and E7, respectively. During the follow-up period, three patients (33%) experienced disease progression. The relative baseline Ct values of these three patients were in the top 4 of all the patients. The sequences of HPV DNA were detected in five (83%) of six samples of the baseline saliva that underwent DNA sequencing, along with several gene mutations, such as TP53,CDKN2A and PIK3CA. This study demonstrates that, in addition to detection and quantification of HPV DNA by RT-PCR, detection by sequencing of HPV-DNA using a customized cancer panel is technically possible.

Induction chemotherapy effects on very advanced (T3/T4) human papillomavirus-related oropharyngeal cancer for participation in hypoxia-directed major de-escalation (30 Gy) definitive treatment trial.

6076 Background: De-escalation trials in human papillomavirus associated oropharyngeal carcinoma (HPV+ OPC) often exclude patients with very locally advanced disease. We previously demonstrated in a Phase II study that for patients with T1-T2 HPV+OPC that de-escalation to 30Gy of definitive chemoradiation based on lack of hypoxia on 18F-FMISO (fluoromisonidazole) PET (ROC Study) is associated with excellent outcomes (JNCI 2021; JCO 2024). Here, we hypothesized that induction chemotherapy (ICT) could be used in locally advanced (T3-T4) HPV+OPC to down-stage patients and make them eligible for de-escalation and simultaneously improve tumor hypoxia. Methods: We conducted a pilot study in HPV+ OPC patients with AJCC v7 T3-T4 and/or large volume N2b-N2c-N3 disease (i.e. pts ineligible for ROC Study (NCT03323563)). ICT – carboplatin (AUC2), paclitaxel (90 mg/m2), and cetuximab (250 mg/m2 after 400 mg/m2 loading dose) weekly for 6 weeks. To be eligible for de-escalation (ROC), after ICT, patients needed to be down-staged (<=T2). 18F-FMISO PET scan done prior to ICT, after ICT, and, if eligible for ROC study, about 2 weeks after start of radiation therapy. If an 18F-FMISO PET scan showed no hypoxia at any time point, no further scans necessary and patients received 30Gy of radiation therapy with 2 cycles of chemotherapy concurrently. Primary outcome is 2-year local control rate in 20 evaluable patients (description only in this pilot study). This abstract reports only on the outcomes of the ICT portion of the study. Results: 20 patients were accrued 3/2023-12/2023. Median age - 70 years old (46-88); Male – 95%; ECOG PS 0 – 80%. Tumor stage – T3 (70%); T4a (30%); N2b (70%); N2c (30%). All 20 patients had pretreatment hypoxia by 18F-FMISO. Of the 17 evaluable patients post ICT, 14 (82%) had no hypoxia on post ICT scan (other 3 still receiving ICT). Of 3 patients with hypoxia after ICT, 2 had resolution 2 weeks into radiotherapy, and 1 patient is still pending intra-treatment scan. All 17 evaluable patients had a significant enough of a response anatomically to allow treatment on the ROC Study. All patients to date were able to receive 2 cycles of cisplatin (100 mg/m2) without dose or treatment adjustment. Conclusions: Preliminary results suggest that ICT can allow more advanced tumors (T3/T4), that are typically excluded from de-escalation studies, to be de-escalated and may eliminate tumor hypoxia in a large proportion of cases, but a larger study is needed to confirm these results. Further followup of outcomes (2 year local control rate) is still needed. Clinical trial information: NCT05491512 .

Intra-treatment hypoxia directed major radiation de-escalation as definitive treatment for human papillomavirus-related oropharyngeal cancer.

6007 Background: We previously reported that surgery to the primary site with hypoxia-directed de-escalated radiation to the neck for human papillomavirus associated oropharyngeal carcinoma (HPV+ OPC) can lead to excellent oncologic outcomes. We now report the results of a successor multi-center phase II trial of hypoxia-directed de-escalated chemoradiotherapy without surgery for HPV+OPC. Methods: HPV+ OPC (T0-2/N1-N2c/AJCC 7th) patients were eligible for enrollment. Tumors without evidence of hypoxia on 18F-FMISO (fluoromisonidazole) PET received de-escalated chemoradiation to 30Gy while those with hypoxia received chemoradiation to 70Gy. The primary objective was achieving a 2-year locoregional control (LRC) of 95% (failure was locoregional recurrence where surgical salvage was unfeasible) with a 7% non-inferiority margin. We enrolled a total of 158 subjects upfront to account for a 5% loss due to death (of reasons other than cancer) or follow-up. Secondary objectives were local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS), toxicities, and patient-reported MD Anderson Dysphagia Inventory (MDADI) scores. LF, RF, and DM were estimated using the Cumulative Incidence Function, and OS was estimated using the Kaplan-Meier method. Results were reported up to 1/31/2024. Results: From 4/28/20-4/17/23, 158 HPV+ OPC patients were enrolled where150 patients were eligible for analyses. Patient characteristics: Tonsil (43%); Base of Tongue (47%); unknown primary (10%); >/=10 pack years (22%); T0 (9%), T1 (44%), T2 (47%); N1 (14%), N2a (11%), N2b (59%), N2c (16%). 111 (74%) received 30Gy; 95% cisplatin. With 24 months (8-43) of median follow-up, the 2-year LF, RF, DM rates were 4.2%, 6.9%, 2.0%, respectively. The 2-year overall survival probability was 99%. Only 2 patients could not undergo salvage surgery [one 30Gy (second recurrence); one 70Gy (M1)], both received systemic therapy with durable response. Acute grade 3-4 toxicities were 32% (67% neutropenia). Mean MDADI scores: 92.93 (baseline); 68.24 (3 weeks), 91.45 (4 months) after chemoradiation. Conclusions: These early data indicate that major de-escalation to 30Gy based on hypoxia status achieved significant toxicity reduction without compromise in survival for HPV+ OPC treated with chemoradiation without surgery. Clinical trial information: NCT03323463 .

A Case of Cystic Lymph Node Metastasis from Human Papillomavirus-related Oropharyngeal Cancer That Was Diagnosed After Resection of a Second Branchial Cleft Cyst

A Case of Cystic Lymph Node Metastasis from Human Papillomavirus-related Oropharyngeal Cancer That Was Diagnosed After Resection of a Second Branchial Cleft Cyst

Prevention of human papillomavirus-related oropharyngeal cancer

Prevention of human papillomavirus-related oropharyngeal cancer

Temporal Incidence and Patterns of Distant Failure for Human Papillomavirus (HPV) Related Oropharyngeal Cancer

HPV related oropharyngeal cancer (HPV-OPC) enjoys improved treatment outcomes relative to non-HPV related disease but suffers from similar rates of distant metastases (DM) following treatment. Emerging data supports radical intent therapy for oligometastatic relapsed HPV-OPC, suggesting early diagnosis of DM may be beneficial to outcome. We assess temporal patterns in distance relapse to investigate rationalization of post treatment imaging. A retrospective single center cohort study was carried out of consecutive HPV-OPC treated with radical intent (chemo)radiotherapy ((CT)RT) between 2011 and 2020. Electronic records were reviewed to identify location and timing of development of DM. Oligometastatic (OM) state was defined as </ = 5 metastasis in one system. A total of 793 HPV-OPC patients were identified with median follow-up 3.15 years (range 0.2-8.9). The median time to recurrence was 15.1 months (range: 2.6-63 months). 87% of DM occurred in the first two years after treatment. Pattern of failure by stage are shown in table 1. Indications for scans performed identifying DM alone were symptoms (66%), follow-up imaging based on previous radiological findings (15%), disease response assessment imaging (15%), and incidental findings (4%). Sites of distant metastasis were lung (64%), thoracic nodes (36.5%), bone (27%), visceral (23%), brain (4%) and skin (2%). The sites of visceral metastasis involvement included liver (92%), Adrenal (18%), kidney (18%), and spleen (9%). Treatment offered to patients with OM alone was best supportive care (46%), palliative chemotherapy (15.4%), palliative RT (23%), immunotherapy (8%), and one patient lost to follow up (8%). SBRT was not available during time period. Median survival following diagnosis was 17.5 months (range 4.4-85.4 months). Despite no routine imaging beyond initial treatment response assessment, we identify a small minority of HPV OPC patients with OM recurrence that is associated with better outcome and occasional long-term cure from aggressive therapy. The majority (69%) of DM occur in the thorax/upper abdomen of patients in the first two years post treatment. This finding supports the potential utility of regular imaging of thorax/upper abdomen during early follow.

Abstract PO-037: Biomarkers for early diagnosis of human papillomavirus-related oropharyngeal cancer

Abstract PO-037: Biomarkers for early diagnosis of human papillomavirus-related oropharyngeal cancer

Investigating women's awareness and perceptions on human papillomavirus infection and oropharyngeal cancer in Italy.

This study explored knowledge, attitudes and behaviors toward human papillomavirus (HPV) infection and oropharyngeal cancer (OPC) among women attending primary care services. The cross-sectional study was conducted from September to December 2022 in adult women attending three primary care services in Italy, who were invited to complete a self-administered questionnaire. Overall, 34.7% of participants know that OPC is HPV-associated; knowledge was higher among women who had personal, familiar or friends' experience of cancer, and who reported to often seek dental care, whereas it was lower in older women. The perception of risk of developing OPC was high for 26.4% of women and was higher in those who had experienced STD, who knew that early sexual debut is a risk factor for OPC, and who considered useful the role of dentists on the provision of information about OPC. Only 22.5% had received HPV vaccination, but 62% intended to receive it in the future. Moreover, 63.2% believe that HPV vaccination is very useful to prevent OPC and only 27% are concerned about health consequences of HPV vaccination. These findings indicate that women's awareness of the role of HPV infection in the development of OPC is not satisfactory and underline the role that dentists might have in improving their patients' awareness on HPV related OPC.

HPV-related oropharyngeal cancer: identifying and quantifying topics of patient interest.

As the incidence of human papillomavirus related oropharyngeal cancer continues to rise, it is increasingly important for public understanding to keep pace. This study aimed to identify areas of patient interest and concern regarding human papillomavirus and oropharyngeal cancer. This study was a retrospective survey of search queries containing the keywords 'HPV cancer' between September 2015 and March 2021. There was 3.5-fold more interest in human papillomavirus related oropharyngeal cancer (15 800 searches per month) compared with human papillomavirus related cervical cancer (4500 searches per month). Among searches referencing cancer appearance, 96.8 per cent pertained to the head and neck region (3050 searches per month). Among vaccination searches, 16 of 47 (34.0 per cent; 600 searches per month) referenced human papillomavirus vaccines as being a cause of cancer rather than preventing cancer. The vast majority of online searches into human papillomavirus cancer pertain to the oropharynx. There are relatively few search queries on the topic of vaccination preventing human papillomavirus associated oropharyngeal cancer, which highlights the continued importance of patient education and awareness campaigns.

Clearance Profile of Circulating Tumor Human Papillomavirus DNA During Radiotherapy Predicts Clinical Outcomes in Human Papillomavirus-Related Oropharyngeal Cancer.

This study aimed to examine whether circulating tumor human papillomavirus type 16 (HPV16) DNA (ctHPV16DNA) can help identify patients with locally advanced HPV16-related oropharyngeal squamous cell carcinoma who may benefit from deintensified treatment. We serially collected blood samples before, during, and after treatment from 22 patients who received 70 Gy radiotherapy alone and longitudinally quantified ctHPV16DNA using droplet digital polymerase chain reaction. We correlated the clearance profile of ctHPV16DNA with clinical outcomes. The percentage of patients with detectable ctHPV16DNA decreased after every 10 Gy of radiotherapy. By contrast, the percentage of patients who later developed treatment failure among patients with detectable ctHPV16DNA gradually increased as radiotherapy proceeded, reaching 100% after 60 Gy of radiotherapy. We defined patients with and without detectable ctHPV16DNA after receiving 40 Gy as having slow and rapid clearance profiles, respectively. All 12 patients with a rapid clearance profile remained disease-free after radiotherapy. Of the 10 patients with a slow clearance profile, three had persistent or progressive disease at response evaluation after radiotherapy and one developed distant metastasis during follow-up (ie, four patients experienced treatment failure). The median follow-up for surviving patients was 38.6 months, and the 3-year failure-free survival rates of patients with rapid and slow clearance profiles were 100% and 58%, respectively (P = .02). Neither baseline ctHPV16DNA levels nor metabolic tumor volume was an independent predictor of the pattern of the clearance profile. In patients with HPV16-related oropharyngeal squamous cell carcinoma receiving radiotherapy, a slow ctHPV16DNA clearance profile could prelude unfavorable outcomes. Monitoring ctHPV16DNA is essential for determining the clearance profile, which might help optimize treatment intensity individually.

Investigation of the diversity of human papillomavirus 16 variants and L1 antigenic regions relevant for the prevention of human papillomavirus-related oropharyngeal cancer in Japan

ObjectiveThis study aimed to investigate the distribution of human papillomavirus 16 (HPV16) variants that contribute to the development of HPV-related oropharyngeal carcinoma (HPV-OPC) in the Japanese population and to evaluate genetic variations in the sequence encoding the L1 antigen region of the viral outer shell that is targeted by existing vaccines and is relevant for designing a prevention strategy to combat the exponential increase in HPV-OPC cases in Japan. MethodsSeventy Japanese HPV-OPC patients treated at Tohoku University Hospital were included in the study. DNA was extracted from formalin-fixed, paraffin-embedded tissue samples. Polymerase chain reaction and direct nucleotide sequencing were performed to determine the nucleotide polymorphisms necessary for the classification of HPV16 variants and to assess genetic diversity in the HPV16 L1 antigen region, including the BC, DE, EF, FG, and HI loops. ResultsThe most common variant of HPV16 was the A4 sublineage (88.6%), conventionally called the Asian type, followed by the A1/2/3 (10.0%) sublineage, classified as the European type. The only nonsynonymous substitution detected in the L1 antigen loop region was p.N181T in the EF loop, which was found in 28/70 (40%) cases. In contrast, no nonsynonymous substitutions were observed in the DE, FG, and HI loops, which are particularly important regions in the antigen loop targeted by existing HPV vaccines. ConclusionThe most common HPV16 variant in Japanese HPV-OPC patients was the A4 subtype. The L1 antigen region is highly conserved, suggesting sufficient efficacy of existing HPV vaccines. These findings provide important information that will aid in the design of an HPV16 infection control strategy using existing HPV vaccines to prevent the spread of HPV-OPC in Japan.

Population-Based Analysis of Trends in Incidence and Survival of Human Papilloma Virus-Related Oropharyngeal Cancer in a Low-Burden Region of Southern Europe.

Introduction: Human papilloma virus (HPV)-related oropharyngeal carcinoma (OPC) can be considered a new subtype of cancer with different clinical characteristics and prognosis than that related to tobacco. Its incidence is increasing worldwide. Its epidemiology has been widely studied in areas such as North America and Northern Europe, but less is known in Southern Europe. Methods: We analyzed the epidemiology of OPC using the database from Girona’s population-based Cancer Registry, in the North-East of Spain, from 1994 to 2018. To analyze differences between neoplasms related to human papillomavirus or not, we determined the immunohistochemical expression of p16 in cases within four time periods: 1997–1999, 2003–2005, 2009–2011, and 2016–2018. Results: Oropharyngeal cancer incidence increased significantly from 2001 to 2018 with an Annual Percentage of Change (APC) of 4.1. OPC p16-positive cases increased with an APC of 11.1. In the most recent period, 2016–2018, 38.5% of OPC cases were p16-positive. European age-standardized incidence rate was 4.18 cases/100.000 inhabitants-year for OPC cancer and 1.58 for those p16-positive. Five-year observed survival was 66.3% for p16-positive OPC and 37.7% for p16-negative. Conclusions: Although with lower burden than in other regions, p16-positive oropharyngeal cancer is increasing in our area and has a better prognosis than p16-negative OPC.

The Impact of Surgical Resectability on Outcomes for Patients Undergoing Primary Radiation Treatment for Human Papillomavirus-Related Oropharyngeal Cancer

Primary radiation therapy with or without chemotherapy (RT/CRT) is the most common treatment for oropharyngeal squamous cell carcinomas (OPSCC), but there has been an increase in transoral surgery (TOS) for T1-2 tumors. Because only a subset of T1-2 tumors are TOS-favorable, nonrandomized comparisons between RT/CRT and TOS could be confounded by indication. We aimed to compare outcomes of potential TOS-candidates versus non-TOS candidates, among patients who underwent RT/CRT for early T-stage OPSCC. For patients treated with RT/CRT for early-stage human papilloma virus positive OPSCC between 2014 and 2018, pretreatment imaging was reviewed by 3 head and neck surgeons, blinded to outcomes, to assess primary-site appropriateness for TOS, and extracapsular extension (ECE) was scored by a head and neck neuroradiologist. We compared outcomes based on surgical favorability pertaining to (1) the primary site tumor alone and (2) the primary site and an absence of ECE. Kaplan-Meier estimates for overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared using the log-rank test, with Cox regression used for multivariable modeling. One hundred and forty-three patients were evaluated, of which 121 were male (84.6%), the median age was 59.4 years, and all of them were p16 positive (100%). The primary site was TOS-favorable in 115 of 143 (80.4%). Patients with TOS-favorable primary site experienced superior 5-year OS (89.8% vs 71.2%, P=.017), DSS (90.4% vs 63.4%, P=.022), and RFS (83% vs 49.4%, P=.04) compared with TOS-unfavorable patients. Similarly, patients with a TOS-favorable primary site and no ECE on imaging 101 of 143 (70.6%), had improved OS, DSS, and RFS (P < .05) compared with TOS-unfavorable patients. In this first study to assess surgical favorability as a prognostic factor among patients with T1/2 p16+ OPSCC, patients with TOS-favorable early-stage OPSCC have better outcomes than TOS-unfavorable patients. This provides valuable prognostic information for patients, and also suggests the risk of confounding by indication in nonrandomized comparisons of treatment modalities.

Patient-reported outcomes in human papillomavirus-related oropharyngeal cancer.

This review explores how human papillomavirus-related oropharyngeal cancer affects health-related quality of life (HR-QoL) and the role patient-reported outcomes (PROs) can play in optimizing treatment. PRO measures (PROMs) are comprehensive, subjective assessments of patients' day-to-day HR-QoL. Developed through a scientifically robust, multistage process, PROMs offer insight into patients' symptoms, function, and satisfaction with care. The use of PROMs can increase symptom awareness, stimulate discussion, and enhance shared decision-making between patients and healthcare providers.

Therapeutic strategies for systemic therapies of human papillomavirus-related oropharyngeal cancer.

Our understanding of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) and its molecular basis continues to evolve and produce important insights into customized therapeutic strategies. Novel therapeutics exploiting HPV-related targets are being evaluated in the incurable setting, while the favorable prognosis of locoregionally advanced disease has stimulated investigation into de-escalation strategies. There is much opportunity for better personalization of standard therapy according to HPV status. This review discusses both current and investigational therapeutic strategies for HPV-related OPC.

The 30 ROC trial: Precision intra-treatment imaging guiding major radiation reduction in human papillomavirus related oropharyngeal cancer.

6019 Background: Our previously published proof-of-concept trial using functional imaging to select patient with human papillomavirus (HPV) oropharyngeal carcinoma (OPC) for radiation de-escalation showed promising results. Here we report the outcome of a larger validation trial using the same paradigm where select HPV+ OPC patients received a definitive dose of 30Gy concurrently with chemotherapy and were subsequently observed. Methods: The trial enrolled patients who had p16+, T0-2, N1-N2c, M0 OPC by AJCC 7th TNM. Patients were required to have resection of the primary site (negative margin not required) or core biopsy of lymph node if unknown primary. In addition to standard positron emission tomography (PET), a pre-radiation dynamic 18F-FMISO (fluoromisonidazole) PET was performed to identify hypoxia in gross nodal disease. Patients with evidence of hypoxia ( &gt; 1.2 tumor to muscle standard uptake value on 18F-FMISO) underwent repeat18F-FMISO PET around 2 weeks into radiation. Patients without pre-radiation hypoxia or with resolution of hypoxia on 18F-FMISO PET received 30Gy with 2 cycles of concurrent chemotherapy (cisplatin 100mg/m2 or carboplatin AUC 1.25 x 4 with 5-fluorouracil 2400 mg/m2). Results: From 11/2/17-1/4/21, 158 HPV+ OPC patients consented and were enrolled on trial. Patient characteristics were as follows: male (90%); ages 36-80 years; T-stage T0(26), T1(77), T2(55); N stage N1(19), N2a(15), N2b(95), N2c(29). Of the 114 patients with pre-treatment hypoxia, 24 had persistent hypoxia and received 70Gy. 128 patients were de-escalated to 30Gy and chemotherapy (86% cisplatin). 6 patients withdrew from trial [3 decided to receive standard of care; 3 refused 18F-FMISO PET]. Acute mucositis rates were 11% grade 0, 59% grade 1, and 30% grade 2, respectively. Acute xerostomia rates were 92% grade 1 and 8% grade 2, respectively. Weight loss was infrequent and only 19% complained of grade 1 and 5% complained of grade 2 weight loss. Six patients experienced grade 3 adverse events (diarrhea (2), syncope (2), vasovagal (1), dysphagia (1)). No patients required PEG tubes. With a median follow-up is 12 months (range: 2 months to 40 months), the 1-year locoregional control, distant metastasis-free overall survival rates were 94%, 100%, and 100%, respectively. Among the 30Gy de-escalated patients, none failed in the primary site. 8 patients had recurrent nodal disease underwent successful salvage surgery of which no additional therapy was given to 4 patients. Conclusions: Major de-escalation to 30Gy using patient specific treatment response based on hypoxia resolution resulted in excellent locoregional control with significant toxicity reduction. Updated results along with detailed correlative analysis will be presented. Clinical trial information: NCT03323463.

De-Escalated Adjuvant Therapy After Transoral Robotic Surgery for Human Papillomavirus-Related Oropharyngeal Carcinoma: The Sinai Robotic Surgery (SIRS) Trial.

Treatment of human papillomavirus-related oropharyngeal squamous cell carcinoma (HPVOPC) results in unprecedented high survival rates but possibly unnecessary toxicity. We hypothesized that upfront surgery and neck dissection followed by reduced-dose adjuvant therapy for early and intermediate HPVOPC would ultimately result in equivalent progression-free survival (PFS) and overall survival while reducing toxicity. This study was a nonrandomized phase II trial for early-stage HPVOPC treated with transoral robotic surgery (TORS) followed by reduced-dose radiotherapy. Patients with previously untreated p16-positive HPVOPC and <20 pack years' smoking history were enrolled. After robotic surgery, patients were assigned to group 1 (no poor risk features; surveillance), group 2 (intermediate pathologic risk factors [perineural invasion, lymphovascular invasion]; 50-Gy radiotherapy), or group 3 (poor prognostic pathologic factors [extranodal extension [ENE], more than three positive lymph nodes and positive margin]; concurrent 56-Gy chemoradiotherapy with weekly cisplatin). Fifty-four patients were evaluable; there were 25 in group 1, 15 in group 2, and 14 in group 3. Median follow-up was 43.9 months (9.6-75.8). Disease-specific survival was 98.1%, and PFS was 90.7%. PFS probability via Kaplan-Meier was 91.3% for group 1, 86.7% for group 2, and 93.3% for group 3. There were five locoregional failures (LRFs), including one distant metastasis and one contralateral second primary. Average time to LRF was 18.9 months (9.6-59.0); four LRFs were successfully salvaged, and the patients remain disease free (11.0-42.7 months); one subject remains alive with disease. The results indicate that upfront surgery with neck dissection with reduced-dose radiation for T1-2, N1 stage (by the eighth edition American Joint Committee on Cancer staging manual) HPVOPC results in favorable survival with excellent function in this population. These results support radiation dose reduction after TORS as a de-escalation strategy in HPVOPC. Transoral robotic surgery can provide a safe platform for de-escalation in carefully selected patients with early-stage human papillomavirus-related oropharyngeal cancer. In this clinical trial, disease-specific survival was 100%, over 90% of the cohort had a reduction of therapy from standard of care with excellent functional results, and the five patients with observed locoregional failures were successfully salvaged.

Timing, number, and type of sexual partners associated with risk of oropharyngeal cancer.

Case-control studies from the early 2000s demonstrated that human papillomavirus-related oropharyngeal cancer (HPV-OPC) is a distinct entity associated with number of oral sex partners. Using contemporary data, we investigated novel risk factors (sexual debut behaviors, exposure intensity, and relationship dynamics) and serological markers on odds of HPV-OPC. HPV-OPC patients and frequency-matched controls were enrolled in a multicenter study from 2013 to 2018. Participants completed a behavioral survey. Characteristics were compared using a chi-square test for categorical variables and a t test for continuous variables. Adjusted odds ratios (aOR) were calculated using logistic regression. A total of 163 HPV-OPC patients and 345 controls were included. Lifetime number of oral sex partners was associated with significantly increased odds of HPV-OPC (>10 partners: odds ratio [OR], 4.3 [95% CI, 2.8-6.7]). After adjustment for number of oral sex partners and smoking, younger age at first oral sex (<18 vs >20 years: aOR, 1.8 [95% CI, 1.1-3.2]) and oral sex intensity (>5 sex-years: aOR, 2.8 [95% CI, 1.1-7.5]) remained associated with significantly increased odds of HPV-OPC. Type of sexual partner such as older partners when a case was younger (OR, 1.7 [95% CI, 1.1-2.6]) or having a partner who had extramarital sex (OR, 1.6 [95% CI, 1.1-2.4]) was associated with HPV-OPC. Seropositivity for antibodies to HPV16 E6 (OR, 286 [95% CI, 122-670]) and any HPV16 E protein (E1, E2, E6, E7; OR, 163 [95% CI, 70-378]) was associated with increased odds of HPV-OPC. Number of oral sex partners remains a strong risk factor for HPV-OPC; however, timing and intensity of oral sex are novel independent risk factors. These behaviors suggest additional nuances of how and why some individuals develop HPV-OPC.

Outcomes of Patients With Single-Node Metastasis of Human Papillomavirus–Related Oropharyngeal Cancer Treated With Transoral Surgery

Regional lymph node metastasis remains an important prognostic factor in patients with oropharyngeal squamous cell carcinoma (OPSCC). Although survival among patients with regional metastasis in human papillomavirus (HPV)-related OPSCC is more favorable compared with patients who are HPV negative, prognostic variables associated with failure in patients with single-node metastasis are not known. To evaluate recurrence and survival in patients with HPV-related OPSCC with single-lymph node metastasis treated with transoral surgery. A retrospective cohort study was conducted of 207 adults with newly diagnosed p16-positive OPSCC and pathology-confirmed single-node disease who underwent surgical resection with or without adjuvant therapy at 2 tertiary academic medical centers from January 1, 2007, to December 31, 2016. Statistical analysis was performed from September 1, 2018, to September 1, 2020. Surgery alone (n = 59), surgery with adjuvant radiation (n = 75), or surgery with adjuvant chemoradiation (n = 73). The primary outcome was regional recurrence. Secondary outcomes included overall survival, any recurrence, and identification of factors associated with regional recurrence and overall survival. Among 207 patients, 178 (86%) were men, with a median age of 57 years (range, 35-82 years) at the time of surgery. Median follow-up was 36.2 months (range, 7-127 months). Regional recurrence occurred in 11 patients (5%). Of these, 1 patient (9%) was lost to follow-up after diagnosis, 1 (9%) was treated with palliative chemotherapy, and 9 (82%) were treated with curative intent. Ultimately, 7 patients received successful salvage treatment, and 3 died with disease. Overall, there were 21 patients (10%) with any recurrence, with 4 patients (19%) experiencing local recurrence, 11 (52%) experiencing regional recurrence, and 6 (29%) experiencing distant metastasis. The 5-year overall survival was 95% (95% CI, 89%-98%) for all patients. Older age (odds ratio [OR], 1.2; 95% CI, 1.1-1.2), advanced T stage (OR, 3.5; 95% CI, 0.9-14.0), and positive margins (OR, 10.9; 95% CI, 1.8-67.5) were associated with increased regional recurrence. Extranodal extension (OR, 0.2; 95% CI, 0.04-0.8), lymph node size greater than 3 cm (OR, 0.2; 95% CI, 0.1-0.7), and adjuvant therapy (OR, 0.08; 95% CI, 0.02-0.4) were associated with decreased regional recurrence. Advanced comorbidities (hazard ratio, 6.20; 95% CI, 1.4-27.7), lymphovascular invasion (hazard ratio, 4.7; 95% CI, 1.0-21.2), and regional recurrence (hazard ratio, 16.0; 95% CI, 3.1-82.0) were associated with worse overall survival. The findings of this cohort study suggest that patients with HPV-related OPSCC and single-node disease undergoing surgical resection with or without adjuvant treatment have excellent survival. Adjuvant therapy appears to improve regional control. Among patients with regional recurrence of OPSCC, there is a high rate of successful salvage treatment.