Patient-Reported Outcome Measures of Psychosocial Quality of Life in Oropharyngeal Cancer Patients: A Scoping Review

Background: Oropharyngeal squamous cell carcinoma (OPSCC) patients are burdened by the effect of the disease process and treatment toxicities on organs important in everyday activities, such as breathing, speaking, eating, and drinking. There is a rise in OPSCC due to human papilloma virus (HPV)-associated OPSCC, affecting younger and healthier patients and with a better overall prognosis. Emphasis must be shared between oncologic outcomes and the effects on quality of life. While there have been efforts to study global and physical quality of life, the impact on psychosocial quality of life has not yet been specifically reviewed. Methods: A scoping review methodology was employed to explore the emotional, social, and mental quality of life in OPSCC patients and determine the impact of HPV status or treatment modalities. Results: Eighty-seven full-text articles were evaluated for eligibility. Fifteen articles met final inclusion criteria. The majority of the studies were conducted in the United States (n = 10) and study methodology was divided between cross-sectional (n = 6), prospective (n = 5), and retrospective studies (n = 4). Four psychosocial quality of life themes were explored: the impact on mental health and emotional wellbeing, social wellbeing and function, stress, and relationship and sexual behavior. Eighteen different patient-reported outcome measures were used, including both general head and neck oncology questionnaires and symptom-specific surveys. Conclusion: There is a paucity of research regarding the effect of OPSCC on patients’ psychosocial quality of life. Learning more about this component of quality of life can guide outreach programs and multidisciplinary involvement in improving patient care.


Introduction
While the number of head and neck cancer diagnoses is decreasing, the prevalence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing in North America due to human papillomavirus (HPV)-associated disease [1]. Currently, approximately 60-70% of OPSCC is associated with HPV, in contrast to traditional tobacco-and alcoholrelated OPSCC [1][2][3][4].
HPV-associated OPSCC differs significantly from conventional OPSCC. Clinically, these patients are younger and healthier at baseline, with little or no tobacco exposure, and the prognosis is favorable with standard treatments [3][4][5]. As such, psychosocial issues related to head and neck cancer survivorship are increasingly apparent in this patient population, yet remain understudied in the scientific literature [6].
Oropharyngeal cancers originate at keystone areas for breathing, eating, and speech [7]. Patients with oropharyngeal cancer experience stress from facing their cancer diagnosis and intensive treatment regimens, with the added effects on organs essential to the activities of daily living and communication [7][8][9][10]. With improved prognosis for most OPSCC cases, goals are shared between maintaining the excellent overall survival and disease-free survival, and quality of life (QOL) [11]. Recent reviews have summarized ongoing or recently completed clinical trials attempting to de-escalate standard therapies for HPVassociated OPSCC patients to minimize or lessen treatment-related side effects [12,13].
Most reviews assessing health-related QOL in OPSCC patients focus on xerostomia, dysphagia, mastication, and other physical complaints [9,14]. While these are important markers for assessment of post-treatment toxicity, QOL is multifactorial. The World Health Organization defines QOL as "an individual's perception of their position in life, in the context of culture and value system in their life and in relation to their goals, expectations, standards and concerns" [15]. Our definition of QOL should extend beyond physical and functional dimensions and incorporate social and emotional factors. This is especially important in head and neck cancer patients, a population in which the prevalence of diagnosed major depressive disorders is as high as 40% [16]. Head and neck cancer patients are more likely to commit suicide when compared to the general population or to patients diagnosed with 19 other cancers [17,18]. However, the changed demographic and better prognosis of HPV-associated OPSCC patients may lead to a different impact on psychosocial QOL.
There has not yet been a review addressing the psychosocial impact of oropharyngeal cancer on patients. Most research focuses on survival and on physical aspects of the disease, in striking contrast with patient-centered concerns. The primary objective of this review is to assess the broad psychosocial QOL in oropharyngeal cancer patients using patientreported outcome measures (PROMs). Secondary objectives are to determine whether treatment regimens or HPV status play a role.

Methodology
This scoping review seeks to identify the current literature published in this field, examine how the research was conducted, and detail the key factors and gaps in knowledge. We followed the scoping review framework proposed by Arksey and O'Malley, expanded by Levac et al. [19,20]. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews was followed as a complementary guideline [21].

Identifying the Research Question
This scoping review was developed to describe the nature, number, and scope of published research articles examining the relationship of psychosocial QOL in patients with OPSCC using validated patient-reported outcome metrics.

Identifying Relevant Studies
A systematic literature search of PubMed, Embase, PsycINFO, and CINAHL was conducted of all articles published between 1946 and August 2022. Search terms included a combination of appropriate database MeSH terms, subject headings, and keywords for the concepts of oropharyngeal cancer, QOL, patient-reported outcome measures, and different emotional and mental states (Supplementary S1). The search strategy was developed with the assistance of a medical librarian guided by the Joanna Briggs Institute; inclusion and exclusion criteria were determined by population type, concept, and context framework (Table 1) [22].

Study Selection
The titles and abstracts of all identified studies were screened by two independent reviewers (JS, RS), with a senior author available to resolve conflicts not agreed upon by discussion (MH). The abstract screening protocol was discussed among authors, and criteria defined using Rayyan, a software designed to allow multiple reviewers to independently select studies for inclusion or exclusion [23]. A pilot sample of 20 abstracts was completed to ensure that both reviewers had a common understanding of the inclusion and exclusion criteria ( Table 1). All article abstracts were screened in increments of 100-200 articles to regularly check inter-rater reliability and ensure consistent results.
The full-text articles were screened by two reviewers (JS, RS) with more refined criteria (Table 1). Articles were included if they were studies published in peer-reviewed journals with a population of adult patients with OPSCC who are undergoing or completed treatment for their disease (surgery, chemotherapy and/or radiation therapy (RT)). The included studies reported on QOL with validated patient-reported outcome metrics, and at least one component of psychosocial QOL was a primary or secondary outcome of the paper. The reference lists of eligible studies were also reviewed to identify any further studies that had been missed in the electronic searches.

Data Extraction
From the full texts, two authors (JS and RS) extracted the following data: author(s), year of publication, study design, study location, participant characteristics, PROMs em-ployed, psychosocial QOL concepts discussed, and important findings. The psychosocial theme content analysis was compiled using NVivo software and inter-rater reliability was calculated [24]. Risk of Bias was assessed using the National Institutes of Health Quality Assessment Tool by two independent reviewers (JS and RS) [25]. Disagreements were resolved by discussion and by consulting a senior author (MH) to resolve remaining discrepancies. Prior to submission, the search was repeated and an additional two articles were included in the analysis. New articles identified since the primary search were screened and data extraction was performed by the same reviewers jointly to ensure agreement.

Collation, Summarizing and Reporting the Results
The data from the included studies were collated and included study demographics, PROMs employed, and psychosocial theme (mental health and emotional wellbeing, social contact, stress, and interpersonal relationships).

Study Population and Demographics
The study selection process is outlined in Figure 1. The databases yielded 2630 citations (Medline: 933, Embase: 1343, PsycINFO: 308, CINAHL: 39), reduced to 1603 articles after removing duplicates. Of these, 87 full-text articles were deemed to be eligible for full-text review. There was a 96.9% inter-rater reliability between the two screening authors (JS and RS). Cohen's kappa was calculated at 0.73, representing substantial agreement [26]. Fifteen articles met eligibility criteria. Their references were screened, but no further articles met inclusion criteria. The included studies had varied study designs, cross-sectional (n = 6), prospective (n = 5), and retrospective (n = 4). The majority of the studies were conducted in the United States (n = 10), with the remainder from Australia (n = 3), and single studies from both Sweden (n = 1) and the Netherlands (n = 1). The three studies from Australia were conducted by the same research group using the same cross-sectional methodology and patient cohort. Studies were published between 2013 and 2022. Sample sizes ranged from 24 to 972 patients, with an average of 179 patients per study. The average age of participants was 59 years (range18 to 89). All studies assessed QOL post-treatment at an average of 30.9 months follow-up (range six months to six years).

Quality Assessment
Using the National Institutes of Health Quality Assessment Tool, the majority of the studies were rated as fair (n = 11), with the remainder graded as good (n = 3) and poor (n = 1).

Quality Assessment
Using the National Institutes of Health Quality Assessment Tool, the majority of the studies were rated as fair (n = 11), with the remainder graded as good (n = 3) and poor (n = 1).

Identification of Psychosocial QOL Themes and Thematic Analysis in Oropharyngeal Cancer Patients
The eligible studies reported on four main themes within psychosocial QOL (Table 2), subdivided as follows: mental health and emotional wellbeing (n = 10), social wellbeing and function (n = 4), stress (n = 5), and relationship and sexual behavior (n = 3). The content analysis of psychosocial QOL themes conducted by both reviewers yielded a Cohen's kappa correlation coefficient of 0.77, demonstrating substantial agreement.

Mental Health and Emotional Wellbeing
The mental health domain comprised studies addressing impacts on depression, anxiety, mood, and emotional function.
Only one study by Kaffenberger evaluated patient mental health after different treatment modalities [27]. This retrospective cohort study compared patients with advanced oropharyngeal cancer treated with primary chemoradiotherapy (CRT) (n = 44) to those treated with surgery with adjuvant RT or CRT (n = 29) and found no significant difference in depression or anxiety scores between the two cohorts, using the PHQ-8 and GAD-7 PROMs, respectively.
The studies that evaluated mental health at different time points noted improvement in mental health scores over time. Janz's prospective cohort study exploring differences between HPV-associated OPSCC patients (n = 21) and HPV-negative oral cavity cancer patients who smoke (n = 17) found that, at 12 months, the HPV-associated OPSCC cohort had an improved depression score on the CES-D [28]. Rajeev-Kumar conducted a retrospective analysis of OPSCC patients treated with RT (n = 69) using the University of Washington QOL (UW-QOL) questionnaire and noted that anxiety and mood scores improved at 12 months compared to pre-treatment values [29].
Berg performed a cross-sectional study comparing BOT cancer patients (n = 190) to tonsillar cancer patients (n = 405) and to the general population (n = 190) [30]. This research identified better emotional function in the patients with HPV-associated OSPCC than in the HPV-negative patients on the EORTC QLQ-C30. Qualliotine's retrospective review of OPSCC patients (n = 69) noted that a lower proportion of HPV-associated OPSCC patients use anti-depressants [31]. Korsten prospectively compared HPV-positive and HPV-negative OPSCC patients and identified greater post-treatment emotional function in the former group using the EORTC QLQ-C30 and the EORTC Head and Neck Cancer module (EORTC QLQ-HN35) [32]. Lee found decreased anxiety (p = 0.005) but no significant difference in mood (p = 0.288), using the UW-QOL scale in 25 HPV-associated OPSCC patients treated with neoadjuvant chemotherapy and transoral robotic surgery (n = 25) compared to a normative cohort [33].
Several other studies did not associate worsening mental health with HPV status (Qualliotine on CES-D initial screen, Rajeev-Kumar on UW-QOL, and Shinn using both the PHQ-9 and the CES-D) [29,31,34]. Shinn performed a prospective cohort study on 130 patients with OPSCC [34]. Casswell et al. did not compare their data of their HPVassociated cohort to HPV-negative patients [27,35,36]. Casswell and McDowell studied the same 136-patient, HPV-positive OPSCC cohort treated with CRT in their crosssectional studies, using the Patient-Reported Outcomes Measurement Information System (PROMIS ® ) Anxiety and Depression questionnaires [35][36][37].

Social Wellbeing and Function
The social wellbeing and function domain comprised studies addressing impacts on social quality of life, social contact, and social eating.
Berg did not identify any significant difference in social domain of the EORTC QLQ-C30 or in the EORTC QLQ-HN35 scores in BOT OPSCC patients who underwent different treatment modalities [30]. Kaffenberger did not identify differences in UW-QOL social scores when comparing CRT to surgery with adjuvant RT or CRT [27]. However, this study did establish that the mean dose of RT delivered to the ipsilateral parotid gland correlated with worse social scores. Dziegielewski performed a prospective cohort study exploring swallowing, speech, and QOL outcomes after transoral robotic surgery in 81 patients with OPSCC, using the Head and Neck Cancer Inventory (HNCI) [38]. The social QOL domain declined immediately after surgery, reaching a nadir at three months; however, this domain recovered and was similar to baseline results at one-year post-therapy.
Comparing HPV-positive and HPV-negative patients, Korsten identified better social functioning at baseline, which worsened to a greater extent during treatment, and recovered better and more quickly at follow-up compared to patients with an HPV-negative cancer [32]. However, mixed-model analysis did not demonstrate a significant difference between HPV-positive and negative patients on social contact and social eating domains. There was no difference in social scores in HPV-positive and HPV-negative patients in the two studies that performed this comparison (Berg, Dziegielewski) [30,38].

Stress
Stress was a diverse theme within this scoping review, with five studies discussing four stress-related concepts: fear of cancer recurrence [35,39], overall attitude/bother or satisfaction with function [38], decisional regret [39,40], and cancer worry [28].
Casswell employed the Fear of Cancer Recurrence Inventory and found that this fear was present in over half of the patients, with younger patients more likely to report this stress [35]. Fear of cancer recurrence was also associated with lower global QOL, higher symptom interference with daily activities, and greater anxiety and depression scores [39]. This study used a patient perspective questionnaire, a measure developed by the researchers based on previously validated metrics.
Dziegielewski identified a significant difference in change in overall attitude in the Head and Neck Cancer Inventory (HNCI; a measure capturing patients' ratings of their function and how much they are bothered by that function) in patients who received adjuvant RT (p = 0.003) and those receiving adjuvant CRT (p = 0.04) compared to those without adjuvant treatment [38]. There was no difference in overall attitude in HPV-positive or HPV-negative patients (p = 0.56).
The study by Janz used the Assessment of Survivor Concerns instrument to compare cancer worry in HPV+ OPSCC patients with smoking oral cavity cancer patients and found that there was no statistically significant difference in cancer worry score (p = 0.1) [28]. Cancer worry also decreased over time in both cohorts but was not statistically significant (HPV+ OPSCC: 21 to 16, p = 0.11, oral cavity: 16 to 15, p = 0.07).
Goepfert and Shaverdian both examined decisional regret in their cohorts using the Decision Regret Scale [39,40]. Goepfert's cross-sectional study reported an average score correlating to mild decision regret (n = 935, median follow-up 6 years) [40]. A total of 15.5% of the patients did exhibit moderate to strong regret, which was significantly associated with higher T classification, combination treatment (surgery and RT/CRT), smoking at diagnosis, and high MDASI-HN symptom score (associated with dysphagia symptom). Shaverdian [39] performed a single-arm cross-sectional study of HPV-associated OPSCC patients (n = 24) enrolled in a de-escalation clinical trial protocol (induction chemotherapy and then concurrent CRT with reduced dose RT of either 54 Gy or 60 Gy based on response). Patients were satisfied overall with their treatment, agreeing that they had made the right decision to pursue a de-escalated treatment. No patient regretted the choice or was dissatisfied with their treatment at a median follow-up of 24 months.        were "totally satisfied" with their treatment and its result. 17% said that they were "somewhat satisfied". None had any level of dissatisfaction with the treatment. 92% "strongly agree" that their decision to proceed with de-escalated therapy was the "right decision", 8% "agree". 92% strongly disagreeing to the statement "I regret the choice I made", none "agree" or "strongly agree". 75% "strongly agree" with the statement "I would go for the same choice if I had to do it again", 21% "agree" and the remaining 1 patient selected "neither agree nor disagree". 92% "strongly agree" that their decision to receive de-escalated therapy was a "wise one", with the remaining 8% patients selecting "agree". The fear of disease recurrence was greater than expected in 42%, as expected in 33% and less than originally expected in 25%.

Relationship and Sexual Behavior
The relationship and sexual behavior domain comprised studies addressing impacts on sexuality and relationship quality/function.
Berg commented on sexuality in the context of a comparison of BOT cancer patients (n = 190) to patients with tonsillar carcinoma (n = 405) and to the general population (n = 190) [30]. Those treated with radiotherapy alone reported worse sexuality scores on the EORTC QLQ-HN35 than those who had surgery with adjuvant CRT (40 versus 28). Overall, BOT cancer patients and patients with HPV-negative disease reported worse sexuality scores than the general population and HPV-positive patients (36 versus 25, p = 0.002 and 48 versus 31, p = 0.05, respectively). There was no significant difference in subgroup analyses comparing subsite (BOT vs. tonsillar), gender, or disease stage.
Casswell utilized the EORTC Sexual Health Questionnaire (EORTC QLQ-SHQ-22) to assess the physical, social, and psychological aspects of sexual health [37]. This study demonstrated that an active sexual life is important to most in this cohort of HPV-associated OPSCC survivors (60%), but there was a much lower rate of recent significant sexual activity (20%). There was no difference in the rating of importance, nor in frequency of sexual activity in patients who knew their cancer was caused by HPV compared to those unaware of the viral etiology. The majority of patients reported no change (57%) or a positive change (27%) in the quality of relationships, while there was a negative impact on the sexual aspect of the relationship in 37% since their diagnosis.
Taberna's prospective research compared the effects of diagnosis and treatment on relationship and sexual behavior in HPV-positive (n = 142) and negative patients (n = 120) [41]. In both groups, they found a high satisfaction with their relationship in elements such as honesty with their partner, lack of regret, confidence in the future of the partnership, and having an overall happy relationship, using the Dyadic Adjustment Scale. There was a significant decrease in frequency of sexual activity at 6-month follow-up for both cohorts (p < 0.01).

Association of Psychosocial QOL and Treatment Modality
Berg reported no difference in depression, anxiety, or social quality of life scores when comparing OPSCC patients treated with primary CRT versus surgery with adjuvant RT/CRT [30]. Kaffenberger showed that patients receiving higher doses of RT to the ipsilateral parotid gland experienced higher anxiety levels and worse social function [27]. Goepfert's study sub-analyzed decision regret based on treatment modality and found that receiving combined treatments (primary CRT or surgery and adjuvant RT/CRT) was an independent predictor of decisional regret [40]. Dziegielewski demonstrated significant differences in overall attitude in patients who received adjuvant RT (p = 0.003) and adjuvant CRT (p = 0.04) compared to those without adjuvant therapy [38].

Association of Psychosocial QOL and HPV Status
A summary of all HPV-related results is included in Table 3. Six studies did not have a non-HPV-associated OPSCC comparator group [27,33,[35][36][37]39]. Table 3. Summary of results comparing HPV-positive and HPV-negative cohorts. Bolded = significant results.
Depression decreased significantly over time for the HPV-positive OPSCC patients (12 to 9.9, p = 0.03) and non-significantly in the oral cavity patients (14 to 9.73, p = 0.1) from baseline to 12 months. Table 3. Cont.

Study HPV-Related Results
Korsten, 2021 [32] Emotional functioning was significantly different between HPV-positive and negative patients: average scores were equal at baseline and in close follow-up (6 weeks and 3 months), but scores improved more in HPV-positive patients (p = 0.039).
Rajeev-Kumar, 2019 [29] There is no statistically significant relationship between anxiety or mood and human papillomavirus infection status (p = 0.089 for anxiety; p = 0.731 for mood).
Shinn, 2016 [34] There was no significant difference in depression scores between HPV-positive and HPV-negative patients.
Cancer worry decreased non-significantly over time in both the HPV-positive OPSCC patients (2.8 to 2.4, p = 0.11) and the oral cavity patients (3.2 to 2.7, p = 0.07).

Relationship and sexual behavior
Taberna, 2017 [41] At baseline, there was no statistically significant differences in levels of relationship distress between HPV-positive and HPV-negative patients. At 6 months follow up, a non-significant trend was noted of higher distress in the affection expression subscale of the DAS for HPV-positive patients compared to HPV-negative. 38% of HPV-positive patients reported that their relationship with their partner had stayed the same, and those who reported a change felt it was positive. 70% of partners reported favorable changes in their relationship since diagnosis. A higher proportion of partners reported more stress in their relationship since the cancer diagnosis than the patients (39% versus 14%, p < 0.01). Approximately a quarter of patients blamed themselves for their cancer diagnosis or felt guilty about exposing their partner to HPV. 14% of partners felt guilty for possibly exposing their partner to HPV or were concerned that the HPV infection may have been a result of an extramarital relationship (their or their partner's). There was a significant decline in sexual behavior frequency in both HPV-positive and HPV-negative cohorts (Primary text: Figure 2, p < 0.01). Six studies reported specific mental health and emotional wellbeing-related results for HPV-associated OPSCC patients. Berg and Korsten noted better emotional functioning in the HPV-positive cohort and Janz described a significant decrease in depression scores in the HPV-positive OPSCC cohort, without a significant decrease in the oral cavity cancer patients [28,30,33]. In the studies by Qualliotine, Rajeev-Kumar, and Shinn, no significant differences in mental health scores between HPV-positive versus HPV-negative cohorts were identified [29,31,34]. In the aforementioned studies, Qualliotine focused specifically on the mental health components of depression, Rajeev-Kumar on mood and anxiety, and Shinn on depression [29,31,34].

No comparison
Berg reported better social functioning in the BOT OPSCC patients who were HPVpositive, using the EORTC QLQ-C30, while Dziegielewski did not find any difference in social function or social attitude between HPV-positive and negative cohorts, using the Head and Neck Cancer Inventory (HNCI) [30,38]. Korsten found that the HPV-positive cohort had worse social functioning during the treatment but recovered faster and to a greater degree in follow-up [32].
Dziegielewski found no difference in overall attitude based on HPV status, and Goepfert did not identify any difference in decisional regret in HPV-associated or nonassociated patients [38,40]. There was a non-significant decrease of cancer worry at 12-month follow up for both the HPV-positive OPSCC patients and the oral cavity cancer patients described by Janz [28].
Taberna conducted the sole study describing the effect of HPV on relationship, finding no difference at baseline, but higher distress, though not significant, in the HPVpositive patients [41].

Discussion
This scoping review aimed to understand the landscape of published literature on the psychosocial QOL in oropharyngeal cancer patients and determine whether treatment regimens or HPV status play a role. Despite the rise in OPSCC globally and the current efforts to de-escalate treatments to allow for better QOL outcomes with long-term survival, this review identified a lack of observational research in this field.
The main mental health and emotional wellbeing theme findings are heterogeneous within the ten different studies. Interestingly, Janz, Berg, Qualliotine, and Korsten's research all identified better mental health and emotional scores in patients with HPV-associated disease when compared to non-HPV-associated head and neck cancers (oropharyngeal or oral cavity) [28,[30][31][32]. In contrast, Rajeev-Kumar and Shinn did not find an association with HPV status and mental health scores [29,34].
Within the social wellbeing and function domain, there were significant positive findings. Kaffenberger identified worse social scores in patients with higher RT doses to their ipsilateral parotid gland, and Dziegielewski found that post-operative social scores reached a low at three months but returned to baseline after one year [27,38]. Korsten noted that HPV-positive patients had better social functioning at baseline, worsened during treatment, but recovered to a greater level [32]. It is unclear why HPV-associated OPSCC patients have a greater toxicity burden from treatment, yet recover more quickly and better than HPV-negative patients; however, this is consistent with other research [42,43].
The stress category that emerged from the thematic analysis comprises four diverse concepts. These different feelings were identified in select subgroups within each study: younger patients and those with lower global QOL, higher symptom interference scores, and worse mental health scores had greater levels of fear of cancer recurrence [35,39]. A worse overall attitude/anxiety with function was found in patients receiving adjuvant therapy [38]. Greater decisional regret was reported in patients with higher T classification, those receiving combination treatment, smokers, and those with more dysphagia-related symptoms [39,40]. There was no difference in cancer worry scores between the groups compared (HPV-associated OPSCC patients vs. oral cavity cancer patients) [28].
The three studies focusing on relationship and sexual behavior employed three different PROMs, creating a challenge in comparison. Interestingly, none of the studies identified significant differences in their scores based on HPV status [30,37,41]. However, Taberna did learn that 28% of patients felt guilty about exposing their partner to HPV.
A secondary objective was to identify the impact of different treatment modalities on psychosocial QOL; however, only three studies addressed this topic. Kaffenberger compared advanced stage OPSCC patients treated for curative intent with CRT (nonsurgical cohort) to surgery and adjuvant RT or CRT (surgical cohort) [27]. Social scores from the UW-QOL questionnaire and depression and anxiety-specific PROM screening did not demonstrate differences between the two treatments. Of note, patients who received higher doses of RT to the ipsilateral parotid gland experienced higher anxiety levels and worse social function. Goepfert's study demonstrated a significant relationship between decisional regret scores and multimodality therapy [40]. While the cohort undergoing surgery and adjuvant therapy had the highest level of decisional regret, this represented few patients within the study and thus must be interpreted with caution (n = 17, 1.8% of study population). Shaverdian's patients were enrolled in the CCRO-22 clinical trial and treated with neoadjuvant chemotherapy and de-escalated CRT based on individual response, reporting excellent decision regret outcomes [39]. The lack of a control group nonetheless limits analysis of psychosocial impact based on treatment modality.
With the rise in HPV-associated OPSCC, it is important to search for significant differences within the HPV-positive and HPV-negative cohorts. Higher emotional and social functioning and significant improvement in depression over time were found in the HPV-positive patients [28,30,32]. No significant differences were found in multiple other studies, and, specifically, no association of HPV status with any HNCI QOL domains [38], mood scores [29,31,34], decisional regret [40], or levels of relationship distress [41].
Within the thematic analysis, multiple PROMs were used for an individual symptom. It is clear that there is no standardized, uniform mental health survey specific for head and neck oncology patients, given that the ten studies within this review used eight different PROMs reporting on mental health or emotional well-being. The heterogeneity of PROMs utilized poses a difficulty in comparing outcomes. A recent study comparing different depression and anxiety PROMs in head and neck cancer patients found the prevalence of moderate and severe symptoms differed between surveys within the same patient cohort (using the Edmonton Symptom Assessment Scale, PHQ-9 and GAD-7) [44]. A meta-analysis performed by Krebber found that 8-24% of oncology patients suffered from depression, but these values were variable based on cancer type, treatment phase, and the screening instrument used to measure depression [45]. Similarly, one of the studies included in this review reported a significant association of depression and overall survival in multivariable modelling using the PHQ-9, while there was no significant risk for mortality using the CES-D [34]. While PROMs are valuable, establishing standard, agreed-upon metrics tailored to the head and neck patient population will be an important future goal to create comparable research outcomes and to decrease survey fatigue [46].
Many completed or ongoing clinical trials are attempting to change the standard treatments for HPV-positive OPSCC and reduce the treatment-related secondary effects [4,12,13]. Patients can be offered a plethora of potential treatments. This era of patient-centered decision making may open the door for further distress due to a shift of responsibility to the patient and the possibility of decision regret [47]. Windon performed a qualitative analysis of treatment decision-making in OPSCC patients who were offered surgery or RT as primary curative intent treatments [48]. Challenges in decision making included the difficulty of incorporating the perceived recommendation of the physician, personal desire for tumor excision, fear of specific secondary effects of treatment, and individual values.
In this scoping review, decision regret was measured in an HPV-positive OPSCC cohort enrolled in a de-escalation clinical trial [39]. At 16 to 30 months post-treatment, patients logged excellent scores on the Decision Regret Scale. In general, late RT-related adverse events, commonly xerostomia and dysphagia, are often the main drivers in post-treatment negative QOL [49][50][51][52]. The goal of lowered RT doses is shared in other trials to minimize these secondary effects [53][54][55]. While Shaverdian's results are positive, it is important to note that this was a small population (n = 24) and a median two-year follow-up may not have provided adequate time to capture the late post-radiation adverse effects. Goepfert assessed a large OPSCC cohort (n = 935) at a median of six years post-treatment, noting mild levels of decisional regret on average [40]. Higher levels of decision regret were associated with higher T staging, multimodal treatment, smoking at diagnosis, and high MDASI-HN symptom score. Decision regret is not yet well studied in OPSCC, despite current efforts to change the standard-of-care treatment, and this is a potential outcome to consider in future research.
There are several limitations to note within this scoping review. While an extensive search of four large databases with diverse target audiences was performed, additional databases may have yielded further results. Grey literature was not explored and published abstracts were not included. This was decided because the lack of full available data would not allow for analysis. Finally, the heterogeneity of themes and patient-reported outcome measures limited the ability to compare studies and draw conclusions.

Conclusions
This review has reported the current status of emotional, social, and psychological QOL in OPSCC survivors. With the rise of HPV-related OPSCC and characteristically younger, healthier patients with improved prognostication, treatment-related morbidity and associated psychosocial impact is now a key area of discussion amongst advocacy groups and oncology professionals alike. Specifically, decisional regret within the category of stress and the impact on relationships and sexuality have been recognized as unique avenues for future research, given the many ongoing clinical trials and the association of OPSCC with HPV, respectively. Few studies have explored these concepts, and no review has focused on these outcomes thus far. This scoping review identified a need to establish a uniform head and neck oncology-specific QOL metric to more consistently assess psychosocial burden within these patients.