Exploring reasons for variations in anxiety after testing positive for human papillomavirus with normal cytology: a comparative qualitative study

Abstract Objective To explore reasons for variations in anxiety in women testing positive for human papillomavirus (HPV) with normal cytology at routine HPV primary cervical cancer screening. Methods In‐depth interviews were conducted with 30 women who had tested HPV‐positive with normal cytology, including 15 with low‐to‐normal anxiety and 15 with high anxiety. Data were analysed using Framework Analysis to compare themes between low and high anxiety groups. Results Several HPV‐related themes were shared across anxiety groups, but only highly anxious women expressed fear and worry, fatalistic cognitions about cancer, fertility‐related cognitions, adverse physiological responses and changes in health behaviour(s). In comparison to those with low anxiety, women with high anxiety more strongly voiced cognitions about the 12‐month wait for follow‐up screening, relationship infidelity, a lower internal locus of control and HPV‐related symptom attributions. Conclusions Receiving an HPV‐positive with normal cytology result related to various emotional, cognitive, behavioural and physiological responses; some of which were specific to, or more pronounced in, women with high anxiety. If our observations are confirmed in hypothesis‐driven quantitative studies, the identification of distinct themes relevant to women experiencing high anxiety can inform targeted patient communications and HPV primary screening implementation policy.


| METHODS
Women aged 24-63 who had tested positive for HPV with normal cytology were recruited to take part in a qualitative study through two NHSCSP HPV primary screening sites in England. The in-depth interviews were conducted with women who had taken part in a survey assessing their anxiety scores (see: doi.org/10.1186/ ISRCTN15113095), who did not report a current anxiety disorder.
Women were purposively sampled to compare the experiences of those with low-to-normal versus high anxiety (indicated by a score of ≤38 vs. ≥49 on the S-STAI-6, 6 respectively). Where possible, they were also sampled to represent a range of demographics (e.g., age, If women completed the survey, they could opt-in to be considered for an interview. The in-depth semi-structured interviews followed a topic guide (see Supporting Information 1) developed using the existing literature, 7,8  Data were coded using the qualitative analysis software NVivo 12 and a 10% check indicated good inter-rater reliability (Kappa ¼ 0.91).
The codes were summarised in a framework matrix to allow for theme comparisons between participants who had scored low-to-normal versus high for anxiety. Framework Analysis 11 was chosen because it facilitates comparisons within and between cases. 12 Greater methodological detail is available (see S2).

Highlights
� To our knowledge, this is the first qualitative study to explore anxiety in women testing human papillomavirus (HPV)-positive with normal cytology at routine HPV primary screening.
� Our comparative qualitative design allowed thematic nuances to emerge between women who had experienced low versus high anxiety following their result.

| Summary of themes
Women's reactions to receiving test results covered five themes: (1) emotional response, (2) cognitions related to HPV, (3) behaviours, (4) disclosure of result and (5) physiological response. Differences between low and high anxiety groups are highlighted throughout.
Quotes are reported with participant number (P) and by anxiety group (low as LA; high as HA).
See Figure 1 for an overview of the thematic comparisons between low versus high anxiety.

| Emotional response
Adverse emotional responses were described mainly by women with high anxiety. Many described experiencing fear or worry shortly after receiving their results, which often related to the development of cervical cancer and/or its potential impact on their family.
It's that panic. You think, oh my goodness. You don't want it [cancer] to happen to you and your family. You want -you want that bubble, you want… to be able to protect -protect it and protect them. (P25, HA) The period between receiving a result and attending the interview was described as 'up and down' (P7, HA), sometimes linked to external triggers (e.g., cancer on TV) or lack of distraction. The period of highest anxiety was reported as lasting between a few days and a couple of months. However, for some, the result remained an 'underlying anxiety' (P2, HA).
The first couple of months it was there. Um then it sort of faded… (P20, HA) Both anxiety groups described 'shock' or 'surprise' immediately after their result because they had no symptoms, had been vaccinated, or were unaware they were being tested for HPV. After the initial shock, some women in the low anxiety group reported little concern or 'relief and reassurance' (P6, LA).

Cervical cancer and the aetiology of HPV
Most women were aware that sexual activity caused HPV.
Others guessed that HPV was caused by poor hygiene or was a symptom of another condition. Most believed that HPV lasted 1-2 years; though a minority believed HPV would stay 'forever' or had been there 'since birth'. Some women wanted to know whether they had 'high-risk' HPV in order to assess their cancer risk. Highly anxious women viewed themselves as medium-to-high risk of cervical cancer.
In the letter they obviously tell you that -that 50 per In contrast, most women in the low anxiety group reported feeling at 'low' risk of cancer and that their result was 'not serious'.
Low perceived risk was related to not having abnormal cells; HPV not being the direct cause of cancer; and HPV not causing problems when dormant or detected early.
Consequences related to developing cancer and its future impact were shared subthemes for both groups; however, these cognitions were prominent in highly anxious women. Some described thoughts about death and cancer treatment.

12-Month screening interval
In the UK, women who receive an HPVþ/normal result for the first or

Sexual impact
Cognitions about the sexual impact of HPV mainly centred round the source of infection and timeline, transmission, the STI label and relationships/infidelity.

Symptom attributions
HPV was widely seen as asymptomatic but some highly anxious women attributed symptoms to the virus, including: the development of a fibroid in the womb; a urinary tract infection; breast milk production; previous genital warts; and thrush. One woman with low anxiety attributed flu-like symptoms and weight gain to HPV. Some women across both groups mentioned symptoms but were unsure if they were connected to HPV, including irregular bleeding, cramp pain, cold sores, fallopian tube pain, cystitis, bleeding after sex, and bladder leaks.

Other cognitions
Fertility-related consequences were mentioned by younger women in the high anxiety group. The HPV vaccine was also discussed and was linked with annoyance about not being offered it by those with high anxiety. Two women discussed the consequences of HPV on their health and mortgage insurance. One had been advised by her insurer that she needed to formally declare her second HPVþ/normal result on her mortgage.
And so he went back to the insurance company and said should she put this down… and their answer was if it was the first one, no -but now she's had two, yes.
And we will not cover her for any treatment. (P28, LA)

| Behaviours
Only women with high anxiety reported changing their behaviour due to HPV. Some reported avoiding sexual intercourse or using condoms. A few attempted to boost their immune system with vitamin supplements, changes to diet, and exercise. One woman reported reducing smoking and another described vaping more to deal with the stress of HPV.
We've not had any sexual intercourse since I got the letter. (P18, HA) For like the first month I was on this really healthy exercise and eating hype to boost my immune system! Women were also asked what they did immediately after they received their result. Many reported using the Internet to search for information on HPV; and highly anxious women described this most extensively, stating it was often 'unhelpful'. Women with low anxiety usually reported putting their result letter to one side, 'skim reading' it (P2, LA), or getting on with their day. Some women described using distraction (e.g., activities or work) to avoid thinking about their result.

| Disclosure of result
Seeking social support was described as a coping strategy to help deal with HPV. Nearly all highly anxious women reported disclosing their result to at least one person; though some delayed disclosure or did not tell certain individuals. Non-disclosure in this context was often because women did not want to burden loved ones. In the low anxiety group, the decision to disclose was mixed. A few women stated that they did not tell anyone because they were not concerned. Those who did disclose sometimes omitted certain information (e.g., the sexually transmitted aspect) due to embarrassment, not wanting to be viewed as 'promiscuous' (P22, LA), or viewing their result as 'personal' (P8, LA). Two women were contemplating whether to disclose their result to a partner.
I think I just tried to put it out of my head and I was a bit embarrassed so I never even discussed it with anyone. (P15, LA)

| Physiological response
Physiological responses were exclusive to highly anxious women.
Soon after their result, some reported crying, sensations in their stomach, and/or sleepless nights. Others described bodily sensations such as shaking and increased heart rate, and nocturia. One reported that she lost her appetite due to her anxiety.

| DISCUSSION
Our findings advance the qualitative literature by exploring psychological response to testing HPV positive with normal cytology at routine HPV primary screening and identifying themes which may be specific to women with high anxiety. Only highly anxious women expressed fear and worry, fatalistic cognitions about cancer, fertilityrelated cognitions, adverse physiological responses, and changes in behaviour(s). In comparison to those with low anxiety, they more strongly voiced cognitions about the 12-month wait for follow-up screening, reltionship infidelity, a low internal locus of control and HPV-related symptom attributions.
Similar to other studies, we found testing positive for HPV was linked to cognitions about cervical cancer and feelings of fear and worry. 3 In our study, cancer-related cognitions appeared to be the most dominant theme and primary concern for highly anxious women.
In particular, these women often focussed on the consequences of cancer and expressed cognitions about undergoing cancer treatments or leaving loved ones behind. Further, many highly anxious women considered themselves to be at medium-to-high risk of cervical cancer.
In The sexually transmitted nature of HPV has previously been linked to feelings of stigma, shame, and embarrassment. 4,7,13 To date, most studies have assumed that sexual concerns play a central role in the development of anxiety following an HPV-positive result. Interestingly, however, we found that most sexual cognitions and related feelings of embarrassment were common to both anxiety groups.
Relationship infidelity was the only subtheme which was more pronounced in women with high anxiety. Although they require confirmation using quantitative studies, our findings help tease out nuances pertaining to cognitive versus emotional responses to HPV.
Longitudinal studies also support this notion given that psychosexual distress remains elevated for up to 12-month, whereas general anxiety normalises within 3 months, indicating two distinct psychological pathways. 4,5 Typically, low perceived control is associated with poor health outcomes including adverse emotional response. 14 In line with recent systematic review evidence for HPV, 4 nearly all women in our study reported feeling that they had little or no control due to a lack of treatment or practical prevention methods for HPV. A novel finding was that highly anxious women appeared to focus on internal factors they could use to gain control (e.g., consuming multivitamins), in contrast to women with low anxiety who linked external factors (e.g., fate) to acceptance of HPV. These findings point to individual differences in the interaction between locus of control and coping styles which, in the absence of a viable solution for HPV, may drive feelings of anxiety.
HPV is asymptomatic, yet some highly anxious women believed or questioned whether certain idiosyncratic symptoms may be HPVrelated. Healthcare professionals and screening information materials should highlight the asymptomatic nature of HPV, while encouraging women to monitor for specific cervical cancer symptoms (e.g., unusual bleeding, pain from sex).
Fertility-related cognitions associated with an HPV-positive result have also been identified in previous studies. 7

| Study limitations
Recruitment was linked to routine clinical management at HPV primary screening, ensuring a diverse and well-characterised sample.
However, due to the relatively small numbers within each demographic group, we were unable to explore intersections between demographics and anxiety. We were able to calculate the time (days) between women receiving their result and attending interview, which ranged from 22-76 days. It is possible that this variability in time from result may have introduced heterogeneity in women's recall of events and/or experiences of anxiety. Finally, although we excluded women who reported a current anxiety disorder, we did not measure anxiety scores prior to HPV primary screening, meaning we could not determine whether receiving an HPVþ/normal result was the primary source of their anxiety.

| Clinical implications
To date, cervical screening patient communications and public health campaigns aimed at minimising adverse psychological impacts have 90 - wholly based their content on population research. Our findings begin to build an evidence-base for the development of specific messages targeting the concerns of highly anxious women, which could be included in standard HPV-positive results letters or covered in training for sample-takers or GPs who discuss HPV results with women.

| CONCLUSION
Receiving an HPV-positive with normal cytology result related to various emotional, cognitive, behavioural, and physiological responses; some of which were specific to, or more pronounced in, women with high anxiety. To avoid unintended consequences for women attending HPV primary screening (e.g., unnecessary anxiety and/or adverse behavioural impacts), these distinct themes should be tested in hypothesis-driven quantitative studies and used to guide the development of evidence-based patient communications and screening implementation policy.

ACKNOLWEDGEMENTS
We would like to thank the women who kindly gave up their time to take part in the interviews.