Complementary and alternative medicine use in women with cervical dysplasia and HPV infection: A cross-sectional study

Abstract

Objectives

Current treatment options for cervical dysplasia and HPV infections are limited to surveillance and surgical interventions, with no established conservative therapies. As a result, women may turn to complementary and alternative medicine (CAM). This study aimed to assess the general interest in conservative therapies, determine the prevalence of CAM-use and identify used CAM methods. These factors were compared between women attending a colposcopy unit and those undergoing routine cancer screening.

Methods

This study used a cross-sectional survey design. An assessment form was developed to gather data on patient characteristics and familiarity with CAM therapies. Five hundred twenty-nine patients participated and provided free-text responses on the use of CAM therapies.

Results

More than 85% of participants expressed a general interest in conservative treatment. CAM use and/or familiarity with CAM for the treatment of HPV or cervical dysplasia was reported by eleven patients (2.0%). Methods like Local Vitamin D therapy, topical mushroom (Coriolus versicolor) gel and topical selenium were mentioned most frequently. All CAM users were patients from the colposcopy unit, and they had higher Pap smear results and HPV infections. The gynecologist was the most frequently used source of information.

Conclusions

We observed a high interest in conservative treatment options and a low prevalence of CAM use. The results suggest that healthcare providers need to remain aware of the specific practices described in order to identify potential adverse effects. Clinicians should address them proactively, particularly in patients with HPV infection or cervical dysplasia.

Resumen

Objetivos

Las opciones terapéuticas actuales para la displasia cervical y las infecciones por el VPH se limitan a la vigilancia y a las intervenciones quirúrgicas, sin que existan terapias conservadoras establecidas. Como resultado, las mujeres pueden recurrir a la medicina complementaria y alternativa (MCA). Este estudio tuvo como objetivo determinar la prevalencia del uso de la MCA, identificar los métodos utilizados y caracterizar a las usuarias de MCA, comparando estos factores entre las mujeres atendidas en una unidad de colposcopia y aquellas sometidas a programas de cribado rutinario de cáncer.

Métodos

Este estudio utilizó un diseño de encuesta transversal. Se desarrolló un formulario de evaluación para recopilar datos sobre las características de las pacientes y su familiaridad con las terapias de MCA. Participaron 529 pacientes, quienes proporcionaron respuestas de texto libre sobre el uso de terapias de MCA.

Resultados

El uso de MCA y/o la familiaridad con estas terapias para el tratamiento del VPH o la displasia cervical fue reportado por 11 pacientes (2,0%). Entre los métodos mencionados con mayor frecuencia se incluyeron la terapia local con vitamina D, el gel tópico de hongos (Coriolus versicolor) y el selenio tópico. Todas las usuarias de MCA pertenecían a la unidad de colposcopia, y presentaban valores más elevados en el frotis cervical y una mayor prevalencia de infección por el VPH. También se observó un alto nivel de interés en opciones terapéuticas conservadoras. El ginecólogo fue la fuente de información más utilizada.

Conclusiones

Se observó una baja prevalencia del uso de MCA. Se identificaron métodos específicos de MCA empleados por las pacientes. Es probable que la verdadera prevalencia del uso de MCA esté subestimada en nuestros hallazgos. A pesar de ello, los profesionales sanitarios deben ser conscientes de estas prácticas específicas para identificar posibles efectos adversos. Los clínicos deberían abordarlas de manera proactiva, especialmente en las pacientes con infección por VPH o displasia cervical.

Introduction

Cervical cancer is one of the most frequent malignant tumors in women worldwide.¹ The most important etiology for cervical cancer and its precursors (cervical intraepithelial neoplasia (CIN) and high-grade squamous intraepithelial lesion (HSIL)) is an infection with high-risk types (16,18) of the human papilloma virus (HPV). Although high-risk HPV infection occurs in more than 80% of women at some point in their lives, it does not progress to cervical cancer in most cases.² Most frequently, HPV infections resolve spontaneously within two years.³ Risk factors for developing cervical dysplasia include smoking, nutritional deficiency of folate, vitamin A, C and E as well as immunosuppression.^1,4 There are two accepted prophylactic strategies for the prevention of cervical cancer: (1)HPV vaccines which have demonstrated high efficacy and have been incorporated into the national immunization programs of 60% of WHO member states.⁵ (2) The detection of dysplasia via Papanicolaou (Pap) smear, HPV-screening and colposcopy.¹ Management of CIN and HPV infection is based on active surveillance and surgical therapy.⁶ Since there is currently no conservative treatment, many women are distressed when confronted with an abnormal Pap smear result and/or HPV infection.⁷

In view of patients’ desire for non-surgical treatment options, it is conceivable they will also look out for methods from the field of complementary, alternative or integrative medicine (CAM). CAM is highly frequently used in the field of oncology, often without physicians’ knowledge.⁸ CAM is a broad term that refers to therapeutic and diagnostic disciplines existing outside of conventional health care providers.⁹ Complementary medicine is used alongside conventional medicine and adheres to similarly evidence-based principles.¹⁰ Alternative medicine is often viewed as incompatible with conventional medicine, as its methods are typically perceived to compete with conventional approaches.⁹ CAM users tend to be more educated, of middle age and often have multiple medical conditions.¹¹ According to a recent review on the topic, CAM approaches with evidence supporting their clinical benefits include topical mushroom therapy (Coriolus versicolor), an active ingredient in Papilocare® (Dr. Pfleger Arzneimittel GmbH, 2016, Germany); topical sodium selenite, found in DeflaGyn® (DEFLAMED INTERNATIONAL s.r.o., 2016, Czech Republic); and oral indole-3-carbinol (I3C).¹²

To our knowledge, there is no data on the prevalence of CAM use in dysplasia patients in literature. This study aimed to determine the prevalence of CAM use, identify used CAM methods, characterize CAM users, identify their sources of information, and assess general interest in conservative approaches. Additionally, the study sought to compare the results between patients referred to a gynecologic clinic for colposcopy and those attending routine cancer screening in medical practice.

Methods

Since there was no prior research in this area, we developed an assessment form comprising the following parts (Supplemental Material 1):

• •

  Patient characteristics and lifestyle: age, height, weight, marital status, smoking, HPV-vaccination, history of abnormal Pap smears, CAM use in general, level of education, current Pap smear result, highest Pap smear result, HPV status.

• •

  Familiarity or prior use of methods for the treatment of dysplasia or HPV infection treatment: participants provided open-ended responses and were permitted to report multiple methods. To avoid agreement bias, we chose to use free-text responses rather than asking participants to simply select from the treatment options we proposed. The categorization of therapies identified as CAM was performed based on the work provided by Wieland et al.¹³ DeflaGyn and Papilocare were classified as CAM following the classification by Walsh et al.¹² Similarly we classified Colpofix® (Uriach, 2022, Spain) as CAM. Methods classified as conventional medicine were categorized in accordance with the German S3 Guideline: Prevention of Cervical Cancer.¹⁴ Certain therapies mentioned were either non-specific or could not be definitively classified as either CAM or conventional medicine. An exhaustive list of methods mentioned can be found in Supplemental Material 2.

• •

  Attitudes towards statements: interest in consultations regarding treatment options; sources of information participants used or would use, including naturopaths, gynecologists, and specialists.

• •

  Preferred forms of treatment application: treatment application methods that participants would consider suitable such as self-applied vaginal treatment, gynecologist applied vaginal treatment, Pills, conization, hysterectomy.

The inclusion criteria were an age range of 18–70 years and the ability to understand both written and spoken German. Patients presenting to the colposcopy unit of the Ortenau Klinikum, Offenburg, Germany, were allocated to the first of two groups. The colposcopy unit was certified by OnkoZert, an independent institute commissioned by the German Cancer Society. This specialized colposcopy unit was the only certified facility in Ortenau County and was therefore representative of the Western region of Southern Germany.

The patients were compared to a cohort of individuals assigned to a second group, comprising those who sought care at a gynecological medical center: MVZ Offenburg Ebertplatz, Offenburg, Germany. The primary reason for consultation at this location was not HPV positivity or dysplasia but rather a representative sample of typical patients in German gynecological practice. The study was approved by the Ethics Committee of the University of Freiburg (Approval Number: 23-1385-S2, October 24th, 2023). Written informed consent was obtained from all patients. After approval the study started on December 1st, 2023. Due to the lack of data on this topic, we were unable to perform a sample size calculation. It was agreed that 250 patients in each group would provide a good overview. When the required number of patients had been reached in October 2024, the study was closed. In the colposcopy unit, 259 patients who met the criteria for inclusion and exclusion were approached, and 252 agreed to complete the assessment form (97.3%). At the gynecological practice, 294 patients were asked to participate in the study, and 277 agreed to complete the assessment form (94.2%).

The questionnaire responses were entered into SPSS Statistics for Windows, IBM Corp., 2016, Version 24.0, Armonk, NY: IBM Corp. An alpha level of 0.05 was used for all statistical tests. Chi-square tests were used to assess associations between categorical variables; Fisher's exact test was applied when expected cell counts fell below 5. Metric variables were checked for normal distribution using QQ-Plots. Metric group differences were analyzed using the Wilcoxon–Mann–Whitney test.

Results

Patient characteristics

A total of 529 patients completed the questionnaire, with their characteristics shown in Table 1. Patients in gynecological practice were significantly older and were more frequently married or living with a partner. There were no differences between groups regarding the level of education. Patients from the colposcopy unit were significantly more likely to have an abnormal current Pap smear result, a history of abnormal Pap smears and an HPV infection. Patients from the gynecological practice group were significantly more likely to be vaccinated against HPV. Smoking was more prevalent in the colposcopy unit group.

Table 1.

Characterization and group comparison of patients attending the colposcopy unit and gynecological practice.

Variable	Entire groupN = 529	Patients from colposcopy unitN = 252	Patients from gynecological practiceN = 277	Group comparisonp-Value
Age years
Median	49	46	54	0.003**^,^a
Body mass index kg/m^2
Mean	25.2	24.9	25.5	0.448^a
Relationship, n (column %)
Single/divorced/widowed	134 (26.2)	83 (34.4)	51 (18.9)	<0.001***^,^b
Married/living with a partner	377 (73.8)	158 (65.6)	219 (81.1)
Education, n (column %)
No final examination	3 (0.6)	1 (0.4)	2 (0.7)	0.085^c
Secondary school	277 (52.9)	141 (56.9)	136 (49.3)
University entrance qualification	139 (26.5)	67 (27.0)	72 (26.1)
University degree	105 (20.0)	39 (15.7)	66 (23.9)
Current Pap smear result, n (column %)
Pap I	310 (76.4)	62 (41.1)	248 (97.3)	<0.001***^,^c
Pap II	37 (9.1)	30 (19.9)	7 (2.7)
Pap III	53 (13.1)	53 (35.1)	0 (0.0)
Pap IV	6 (1.5)	6 (4.0)	0 (0.0)
History of abnormal Pap smear result, n (column %)
Yes	146 (28.3)	114 (45.8)	32 (12.0)	<0.001*** ^b
No	369 (71.7)	135 (54.2)	234 (88.0)
HPV infection is documented, n (column %)
Yes	187 (35.3)	165 (65.5)	22 (7.9)	<0.001*** ^b
No	342 (64.7)	87 (34.5)	255 (92.1)
HPV vaccinated, n (column %)
Yes	61 (11.9)	21 (8.5)	40 (15.0)	0.023* ^b
No	453 (88.1)	226 (91.5)	227 (85.0)
Smoking, n (column %)
No	422 (80.5)	183 (73.8)	239 (86.6)	0.001** ^b
1–15 cigarettes/d	88 (16.8)	57 (23.0)	31 (11.2)
More than 15 cigarettes/d	14 (2.7)	8 (3.2)	6 (2.2)
CAM use in general, n (column %)
Yes	161 (30.7)	75 (29.9)	86 (31.4)	0.708^b
No	364 (69.3)	176 (70.1)	188 (68.6)

The difference between the total number of participants and the recorded count is a result of missing responses. The cumulative percentage may fall short of or exceed 100% as a result of rounding.

a

Wilcoxon–Mann–Whitney test.

b

Chi-square test.

c

Fisher's exact test.

*

p < .05.

**

p < .01.

***

p < .001.

Overall, 161 participants (30.4%) reported using CAM in general e.g. homeopathy. General usage showed no association with patient group, age, relationship status, education level, Pap smear results, or HPV infections.

Prevalence of CAM use and CAM methods used

Patients indicated the treatment methods with which they were familiar and/or which they had previously used. Many methods were associated with conventional medicine or could not be clearly classified (Supplemental Material 2). Eleven out of 529 patients (2.0%) reported using or being familiar with at least one specific CAM method. The CAM methods mentioned most were Local Vitamin D therapy, Papilocare and DeflaGyn (Table 2). All eleven patients using or being familiar with CAM methods were exclusively from the colposcopy unit group. Seven of the eleven patients (77.8%) had a Pap smear result >Pap II and nine of them (81.8%) had an HPV infection (Supplemental Material 3).

Table 2.

CAM methods mentioned in free text and their frequency of recognition and/or prior use by patients.

CAM method mentioned	N mentions
Local Vitamin D therapy	3
Papilocare	3
DeflaGyn	3
Hip bath	2
Fasting cure	2
Daily fresh garlic	2
Hypnotherapy	2
Tampon with yoghurt	2
Colpofix	2
Naturopathy	1
Local Vitamin C application	1
Grapefruit seed extract	1
Meditation	1
Food supplements	1
Methylsulfonymethan	1

Multiple responses per participant allowed.

Interest in conservative treatment options and sources of information

The participants’ responses regarding various attitudes are presented in Fig. 1 (and Supplemental Material 4). Interest in consultations about drug options for dysplasia and HPV infections treatment was high in both groups, however it was higher in patients from the colposcopy unit. Those interested were more likely to have a Pap smear result >II (p = 0.02) and an HPV-infection (p < 0.001). Most participants strongly agreed that their gynecologist should inform them about HPV and dysplasia treatments. Regarding this statement, there was no difference between groups found. For both groups, 42.9% strongly agreed or agreed that they had already sought or were interested in seeking information from a naturopath. Individuals from the colposcopy unit showed a significant preference for treatment by a specialist, not necessarily their gynecologist.

Fig. 1.

Attitude towards statements on interest in consultations for drug options in the treatment of cervical dysplasia and HPV infections, and preferred healthcare providers among participants from the gynecological practice and colposcopy unit. ***p < .001; (a) Chi-square test; (b) Fisher exact test.

Preferred treatment approaches

We also asked patients which methods for the prevention and treatment of HPV or dysplasia they would consider suitable. Patients rated their preferences using a scale of four options (Fig. 2 and Supplemental Material 5). Nearly all patients agreed that local vaginal application, either by a gynecologist or themselves, and the usage of pills or drops was suitable. However, opinions were divided regarding conization and hysterectomy. Patients from the colposcopy unit were significantly more likely to have considered hysterectomy (p = 0.041).

Fig. 2.

Agreement with treatment form of participants in gynecological practice (Gyn. Prac.) and colposcopy unit (Colp. Unit). Difference between groups: *p < 0.05; (a) Chi-square test; (b) Fisher's exact test.

Discussion

This study assessed the attitude of patients with cervical dysplasia and HPV infection towards CAM use. The study demonstrates that the prevalence is low with only a few patients (n = 11; 2.0%) aware of specific CAM methods. This usage of specific methods was exclusive to the colposcopy unit despite no difference in general CAM use. The prevalence was much lower than the 37.5% reported among patients with gynecological cancers.¹⁵ We observed that 30.4% of our participants reported using CAM in general, which is lower than the 42% prevalence found in previous studies of the general population.¹⁶ This discrepancy may be attributable to the recruitment setting, as our participants were drawn from a medical care environment rather than the general population or a naturopathic practice.

We hypothesize that the emotional burden in dysplasia patients is less severe than in cancer patients, possibly leading to a lower demand for alternative treatments. While the term cancer is generally well understood by the public, we hypothesize that many women with cervical abnormalities may not fully comprehend their condition, as previous research has shown limited awareness of HPV and its association with cancer.¹⁷

Among the mentioned CAM methods, Papilocare is considered the method with the best clinical benefit.¹² Also, DeflaGyn with its ingredient sodium selenite was mentioned. It has shown promising preliminary results in improving cervical cytology and HPV regression.¹² Although the prevalence of CAM use was low, we showed that those methods are indeed used by patients. Thus, physicians must be knowledgeable about its side effects and potential interactions with other treatments. For example, side effects of sodium selenite include vaginal itching, while Coriolus versicolor may cause vulvovaginal stinging and candidiasis.¹² Other mentioned CAM methods lack clinical evidence or have limited clinical evidence, such as local vitamin D application, which was mentioned three times. This method has only been tested in a small study, showing some antidysplastic effects.¹⁸

Patients in our study who used CAM were exclusively from the colposcopy unit and the majority had abnormal Pap smears and HPV infections. This is consistent with previous reports on general CAM use, which indicate that participants tended to use more CAM when experiencing health impairments.¹¹ Given the small sample of CAM users, a linear regression model could not be performed to explore predictors for CAM use for dysplasia.

We observed that a significant number of women expressed interest in learning about new treatment options. Notably, women with more severe cervical abnormalities were more likely to show this interest. We found that many women exhibited skepticism toward surgical interventions, which is a finding that aligns with previous studies.¹⁹ We showed that the gynecologist serves as the main source of information on treatment options; however, more severely affected patients tend to prefer consultation with a specialist. As in previous studies shown, medical personnel have been found to be a trusted information source regarding HPV related questions.²⁰ We observed a relatively high proportion (42.9%) of patients, particularly those from the colposcopy unit, who were willing to seek guidance from a naturopath. A similar proportion was observed in other studies with breast cancer patients relying on naturopaths and non-medical practitioners for guidance on CAM.²¹

Our study's findings have the following limitations: The recruited participants all received professional medical care. This does not represent the fraction of the population who exclusively seek information from a naturopath or from other sources. As naturopathic treatments vary regionally, findings likely reflect practices specific to southwestern Germany. The use of a validated questionnaire to assess CAM prevalence would have been preferable, but this was not feasible due to the limited data available in this field. The question regarding treatment measures was phrased openly, leading many participants to respond with conventional medical treatments. A more specific inquiry focusing on CAM measures could have yielded more targeted responses. Moreover, patients provided responses to the list of methods in free text. It is possible that some participants chose not to answer this question due to a lack of motivation. This highlights how little significance many individuals assign to the topic. If simple yes/no questions had been used to assess CAM methods, we might have received more responses; however, this approach could have also increased the risk of acquiescence bias. Therefore, we hypothesize that the prevalence of CAM use is likely underestimated, but certainly not overestimated. Since only eleven patients reported using a CAM method, our sample size was too small to perform a logistic regression. Studies with a greater number of participants should be conducted to assess the predictors for CAM use.

Conclusion

In conclusion, we found a low prevalence of CAM use for the treatment of cervical dysplasia and HPV infection. Although the prevalence found in this study may be underestimated, it is still noticeable that most CAM users were from the colposcopy unit and had greater health impairments.

Specific methods mentioned by the participants with strong clinical evidence were DeflaGyn and Papilocare. However, methods with minimal evidence, such as the local application of vitamin D, were also mentioned. For most of the participants, gynecologists were the primary source of information on treatment options; however, naturopaths were also consulted. We found considerable skepticism towards surgical interventions. Our findings underscore a strong interest in conservative treatment options and support the need for larger studies to better assess the prevalence and types of CAM methods used. Finally, we emphasize that gynecologists should stay informed about emerging treatments and actively educate patients, particularly in patients with concerns related to HPV or Pap test results.

Authors’ contributions

• •

  Julius Brandt: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Visualization, Writing – original draft

• •

  Felix Momm: Conceptualization, Writing – review and editing

• •

  Anja Schilberg: Investigation

• •

  Karsten Münstedt: Conceptualization, Resources, Project administration, Validation, Writing – review and editing, Supervision, Investigation

Statement of ethics

All procedures for data collection and analysis were conducted in accordance with applicable laws and institutional guidelines. The study was approved by the Ethics Committee of the University of Freiburg (Approval Number: 23-1385-S2, October 24th 2023).

Patient consent

The privacy rights of all participants were protected, and informed consent was obtained.

Declaration of generative AI and AI-assisted technologies in the writing process

This paper benefited from the use of ChatGPT-4 for language refinement and translations. Each sentence was carefully reviewed and edited to ensure accuracy and appropriateness. The authors take full responsibility for the content.

Funding

This study was not supported by any sponsor or funder.

Conflict of interest statement

The authors have no conflicts of interest to declare.

Data availability

The datasets will be made available to reviewers, editors, and readers upon request.

Acknowledgements

The authors would like to thank the participants in the study. We thank Petra Brandt, Elke Fautz, Jörn Pons-Kühnemann and Christine Scheibelhut for their contributions.