Prevalence and Rapid Screen Method of Diagnostic Criteria for Psychosomatic Research Syndromes in Human Papillomavirus-Infected Patients

Human Papillomavirus (HPV) is a sexually transmitted virus that is very common and is responsible for causing more than 99% of cervical cancers [1]. In recent years, studies using self-rated scales have shown that there are psychosocial factors that affect HPV-positive patients [2, 3], and only one study used a structured clinical interview to assess mental disorders (e.g., Diagnostic and Statistical Manual of Mental Disorders [DSM]) [4]. However, these studies did not assess psychosomatic symptoms or provide specific guidance for clinical interventions.

The DSM is considered as the gold standard in psychiatry [5, 6]. However, it may not always be effective at detecting psychological problems that are less severe, known as “subclinical” problems [7]. A new Diagnostic Criteria for Psychosomatic Research (DCPR) assessment tool was developed in 1995 [8] to address this issue. 2017, a revised DCPR version was released, including a semi-structured interview [9]. Reports have shown that the DCPR has clinical utility in (1) subtyping medical patients, (2) identifying undetected syndromes, (3) evaluating the burden of somatic syndromes, and (4) predicting treatment outcomes and identifying risk factors [10]. The DCPR has been used to supplement DSM diagnosis in oncology [11], dermatology, endocrinology, cardiology [10, 12‒14], and gastroenterology studies [15, 16]. Its reliability and advantages relative to the DSM were previously verified [17], and its clinimetric properties were confirmed [18].

It is essential to assess the psychological health of patients who are HPV-positive. However, routine assessment can be time-consuming (i.e., more than 30 min) and requires a specialized psychological clinic referral. Structured interviews require specialized clinical experience and skills [19]. Therefore, doctors who do not have specialized psychological training can use a more rapid screening method. In this study, we investigated the prevalence and psychosocial factors that contribute to DCPR syndromes in patients with HPV infection. We used multivariate analysis to develop a rapid screening method to help doctors quickly identify patients at high risk of DCPR syndromes. This is the first study to examine DCPR syndromes in obstetric and gynecological illnesses worldwide.

This cross-sectional study investigated risk factors associated with DCPR syndromes in HPV infection patients. The study enrolled patients who visited the HPV Special Disease Clinic of the Cervical Diseases Department of Changzhou Maternal and Child Health Care Hospital consecutively from January 2022 to December 2022 and met the following criteria: (1) aged 20–66 years; (2) positivity for one or more HPV types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, or 82; (3) normal or abnormal cytological type; (4) Chinese maternal history; and (5) primary school education or above. Patients who had cervical cancer or any other cancer, hysterectomy, acute or fatal cardiovascular, kidney, liver, nervous system disease, or immune system disease were excluded. Participants in the control group were without HPV infection, the other inclusion criteria and exclusion criteria were the same as the HPV-positive group.

The primary measure to evaluate psychosomatic syndromes was through semi-structured interviews using the DCPR tool [20]. In addition to this, other measures like Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnoses [21], Social Support Rating Scale (SSRS) [22], Simplified Coping Style Questionnaire (SCSQ) [23], and the level of fear were also evaluated [24, 25] (instruments available within the online supplement; for all online suppl. material, see https://doi.org/10.1159/000539471). The sociodemographic and clinical data were collected by a trained psychologist independently.

The statistical analyses were conducted using Empower Stats software version 2.2 (X&Y Solutions, Inc., USA) and R (version 3.4.2; http://www.R-project.org). We compared the sociodemographic and clinical characteristics, including age, educational level, income, occupation status, marital status, infection duration, DCPR, DSM-5, degree of fear, medical history, coping styles, SSRS, and incidence knowledge between HPV-positive and HPV-negative groups using independent t tests or Kruskal-Wallis tests. Similarly, we used the same method to compare DCPR = 0 with DCPR ≥1. χ² test was used to analyze the prevalence of DCPR syndromes and DSM-5 diagnoses. The age, education, income, SSRS, degree of fear, HPV positivity, active coping, passive coping, and infection duration were used to evaluate the associations of psychosocial factors with DCPR syndromes (DCPR ≥1) using univariate and multivariate logistic regression analyses. We also assessed the potential effect of advanced fear on the relationship between DCPR risk and HPV positivity by interaction analysis and obtained odds ratios (ORs) and 95% confidence intervals (CIs). We considered a two-tailed p < 0.05 to indicate statistical significance.

A total of 504 (249 HPV-positive and 255 negative) patients were enrolled in the study, as detailed in online supplementary Figure 1. The demographic and clinical characteristics of the patients were analyzed to determine the risk factors associated with DCPR syndromes in HPV infection patients.

Age, infection duration, degree of fear, DSM-5 diagnoses, and DCPR syndromes showed significant differences between the HPV-positive and HPV-negative groups (all p values <0.05), as detailed in online supplementary Table 1. Among the participants, 141 patients (56.6%) reported at least one diagnosed DCPR syndrome, with the most common syndromes being health anxiety (30.9%, n = 77), irritable mood (26.5%, n = 66), type A behavior (22.5%, n = 56), and demoralization (16.7%, n = 33). Conversely, 44 individuals who tested negative for HPV reported at least one DCPR syndrome, constituting 17.3% of the study population. In contrast, 21 individuals who tested positive for HPV were diagnosed with at least one mental disorder by DSM-5 criteria, accounting for 8.4% of the participants. The incidence of DCPR syndromes was significantly higher in HPV-positive patients than the incidence of DSM-5 diagnoses (χ² = 131.75, p < 0.001). For further details, please refer to the online suppl. Table 2.

The study revealed significant differences between participants with at least one DCPR syndrome and those without regarding age, degree of fear, coping styles, educational levels, income levels, and infection duration (all p values <0.05–0.001), as indicated in Table 1. Further analysis demonstrated that age (33–39 years: OR: 2.37, 95% CI: 1.15–4.90), SSRS score (OR: 0.95, 95% CI: 0.92–0.99), degree of fear (6–10: 4.43, 95% CI: 1.86–10.53), and HPV positivity (OR: 3.51, 95% CI: 2.04–6.04) were independent influencing factors of DCPR syndrome (all p values <0.05), as outlined in Table 2.

We found a significant relationship between fear and HPV positivity when it comes to the risk of presenting at least one DCPR syndrome (see online suppl. Table 3). Our analysis showed that as the degree of fear increased from zero to 1–5 to 6–10, the risk of DCPR syndrome also increased from (95% CI: 0.59–14.54, p = 0.1877) to 6.48 (95% CI: 2.35–17.84, p = 0.003) to 18.94 (95% CI: 7.05–50.91, p < 0.0001), respectively, in the crude model. However, after considering various factors such as age, education level, duration, income, coping style, and SSRS score, the risk of DCPR syndrome still increased in the adjusted model from 1.27 (95% CI = 0.21–7.63, p = 0.7918) to 3.24 (score range = 1–5, 95% CI = 1.01–10.39, p = 0.0477) to 9.91 (score range = 6–10, 95% CI = 3.21–30.62, p < 0.0001), respectively.

Patients with HPV, the most common sexually transmitted disease, are increasingly aware of the link between HPV infection and cervical cancer. In addition to worrying about their health, patients also fear disclosing their test results to their partners, family, or friends due to the stigma associated with the infection. This has led to an increase in anxiety, distress, and shame among patients [3, 26, 27]. In this study, it was found that both depressive disorder and anxiety disorder were more common in HPV-positive patients compared to negative ones. However, the differences were not statistically significant. According to the DSM-5, only 8.5% of the patients displayed symptoms that indicated a psychiatric diagnosis. However, a much higher percentage of patients (56.6%) met the criteria for DCPR syndrome. This suggests that the DCPR can identify subthreshold or subsyndromal disorders related to HPV that may have gone undiagnosed by DSM-5 alone. This finding is consistent with previous research in other medical settings [28, 29].

The prevalence of DCPR syndromes has been studied in patients with various illnesses, revealing different syndromes as the most common. In congestive heart failure patients, the three most common syndromes were irritable mood (12.9%), illness denial (22.9%), and demoralization (15.7%) [29]. In primary care patients, the main DCPR syndromes were maladaptive illness behavior (26.5%), allostatic overload (15.5%), and demoralization (15%) [28]. Patients who underwent coronary artery bypass grafting surgery had type A behavior (14.7%), irritable mood (14.7%), and health anxiety (11.8%) [13]. For migraine, the most frequent syndromes were allostatic overload (29%), type A behavior (10.5%), and persistent somatization (8%) [17]. In HPV-positive patients, the most common DCPR syndromes were health anxiety (30.9%), irritable mood (26.5%), type A behavior (22.5%), and demoralization (16.7%) [30]. These three, along with demoralization, were among the four major psychosocial aspects of a medical disorder in the biopsychosocial model based on clinimetric methods of classification [31].

Health anxiety is a condition where an individual experiences excessive and persistent worrying about their health, often accompanied by intense bodily preoccupations and an inclination to amplify physical sensations [19]. Fortunately, several effective treatments have been identified for this condition, including cognitive-behavioral therapy [30], imagery techniques [32], mindfulness training, and acceptance and commitment therapy. These treatments can be administered individually or in group settings, both in-person or virtually over the Internet, and be efficacious in the short and long term [33].

Demoralization is a term used to describe the feelings of helplessness, despair, and subjective incompetence that people experience when they believe they are not meeting their or others’ expectations while coping with difficulties [34, 35]. Identifying demoralization, which can also manifest as hopelessness in severe cases, can help identify patients who are more susceptible to nonspecific elements of treatment [36]. Cognitive-behavioral therapy combined with WBT, bedside psychotherapy [37], and existential inquiry [38] can be effective in addressing demoralization based on preliminary findings [39].

In this research, it was found that HPV-positive women with a fear level ranging from 6 to 10 had a risk of DCPR that was up to 9.91 times greater than that of HPV-negative women, even when other factors were taken into account [40]. According to the hypnosis theory of Milton Erickson, each person responds to questions based on their inner needs. The degree of fear reported by the participants was influenced by their personality traits, coping styles, and cognitive levels. This, in turn, reflected their attitudes and behaviors toward the disease. As the literature suggests, listening to the patient’s beliefs about the illness and its treatment can help identify inadequate expectations and convictions that may lead to health-damaging behaviors [19]. Therefore, self-reported fear levels could be used as a quick method to screen for DCPR syndrome in outpatients with HPV infection. Further research is needed to determine whether this approach could be applied to other diseases.

The current study has a few limitations that should be considered. First, it was a single-center cross-sectional study that may not accurately represent the general population. Thus, the conclusions drawn from this study need to be validated before being extended. Second, the focus of this study was on the Chinese population, and since HPV-positive rates vary according to race, further well-designed multicountry studies are required. Lastly, this study only examined one illness; future studies should determine if these findings apply to other diseases.

The DCPR tool clinicians administer requires proper training and familiarity with the literature on DCPR. It also requires prior knowledge of a patient’s medical and psychiatric diagnosis, disease course, and treatment history. A joint psychiatric assessment is recommended. This study aimed to fill the gap in knowledge on the use of DCPR syndrome in obstetrics and gynecology illnesses. It also explored a rapid screening method for doctors with no special psychological training rather than simplifying assessment scales or training more psychiatrists, as done in previous research. The findings showed that over 85% of patients with a fear score of 6–10 had at least one DCPR syndrome, and the detection efficiency improved significantly when applying the results of this experiment to the clinic.

We need to investigate further whether the correlation between the level of fear and the incidence of DCPR syndrome applies to other diseases. Furthermore, this method can aid clinicians in rapidly identifying outpatients at a greater risk of developing DCPR syndrome. This would promote efficient and systematic DCPR assessment in various clinical environments.

The authors thank all the subjects and psychiatrist involved in the study, as well as the nonauthor team members Wang Li, Hu Huiwen, and Zhu Haiyan, for collection and preparation of the data presented herein.

The study was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. All participants gave their written informed consent to participate in the study. The Ethics Committee of Nanjing Medical University approved the study with approval No. 2022-491.

The authors have no conflicts of interest to declare.

The work presented here was funded by the Top Talent of Changzhou “The 14th Five-Year Plan” High-Level Health Talents Training Project and the Changzhou Science and Technology Plan (social development science and technology support) project (CE20215023).

X. Cui, L. Ding, and Y. Xu designed the study. X. Cui, L. Ding, and Q. Zhang extracted the data, conducted the study, and wrote the first draft of the manuscript. X. Yuan cross-checked the statistical analyses. C. Rafanelli and S. Gostoli critically reviewed and interpreted the manuscript. Z. Liu and J. Cao are the principal investigators, providing resources and supervising all steps of this project. All authors contributed to the interpretation, reviewed, and edited the manuscript, and approved the submission of the final version.

Xuelian Cui and Lixin Ding are the two first authors and have contributed equally to this work.

The data cannot be shared due to patient confidentiality and privacy concerns. Further inquiries can be directed to the corresponding author.