A prospective observational design was employed to assess pregnant women’s psychological distress before the notification of a positive-HPV-and-normal-cytology result, as well as before the colposcopy evaluation and 2 weeks after. The result notification and colposcopy evaluation were 2 weeks apart.
HPV genotyping and cytology
Two endocervical brush samples were taken from the participants for liquid based cytology (Thinprep) and HPV genotyping (Hybribio), as the co-testing. The cytology results were evaluated according to the Bethesda system as Negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL). An abnormal cytology result was defined as ASC-US or above, and a positive HPV result referred to testing positive for any of the 13 high-risk subtypes. The HPV detection subtypes included 15 high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68) and 6 low-risk types (6, 11, 42, 43, 44 and 81). The infection of high- risk HPV was defined as HPV positive.
From July, 1, 2017 to December, 31, 2017, pregnant women who had entered their second trimester undergoing combined HPV and cytology screening, the ‘co-testing’, were enrolled. Women with previously diagnosed mental illness, younger than 25 years of age, and had any obstetrics complications too serious to continue pregnancy were excluded. The positive HPV results were notified by the first author by phone after the baseline psychological questionnaire was filled out. Most women that were invited to the colposcopy did not further ask the meaning of the screening results over the phone. For the inquiries regarding HPV, the first author responded with the following statements: (a) HPV is highly prevalent; (b) Persistent HPV infection is a prerequisite for cervical pre-malignancy and, eventually, cervical cancer; and (c) Evaluation under colposcopy is an effective way to determine whether there is a lesion on the cervix. The interview via telephone lasted 2-5 minutes per participant. Two weeks after the notification, participants were observed under colposcopy to rule out any cervical lesion and, if high-grade lesion was detected, the biopsy was done with fully consent of the participant, according to the study protocol. The second and third psychological evaluations were done before the colposcopy and 2 weeks after.
We also included a control group who had received a normal co-testing result. The psychological evaluation was done only once before the notification of the result (the baseline).
The psychological distress questionnaire (in Chinese Mandarin language) included the Generalized Anxiety Disorder-7 scale (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9) for anxiety and depression. We selected these two screening instruments considering that (a) they can easily be completed within 5 minutes, (b) questions are referring to symptoms during the last 2 weeks, which is coherent with the notification-colposcopy period, and (c) they were both validated for pregnancy populations, (16-18) as recommended by ACOG and NICE. (19, 20)
Both PHQ-9 and GAD-7 have been developed from the original Patient Health Questionnaire (PHQ) with nine and seven questions each. (21) The PHQ-9 is composed of the nine criteria on which the diagnosis of depression is based in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) (22) and scores can range from 0 to 27, with 5, 10, 15 and 20 representing mild, moderate, moderately severe and severe levels of depressive symptoms. Similarly, the GAD-7 can also be used as a continuous measure with scores ranging from 0 to 21 and cutoff points of 5, 10 and 15 representing mild, moderate and severe anxiety symptoms.
The demographic data and lifestyle factors were also collected, followed by questions regarding screening behavior and knowledge of cervical cancer.
The study was approved by Ren Ji Hospital Ethics Committee (2018). All methods were carried out in accordance with the rules of the Declaration of Helsinki. All participants provided written informed consent.
Continual variables were presented as means (standard deviations, SD) or median (interquartile ranges, P25 ~ P75). Categorical data were presented as frequencies (percentages). Univariate comparisons between HPV-positive and -negative groups were undertaken using the Pearson Chi-square test, exact Chi-square test, T-test, or Mann-Whitney test. Univariate and multivariate logistic regression analysis was employed to identify women’s lifestyle factors that were associated with HPV positivity. Friedman’s test and the Wilcoxon’s test were employed to detect changes of psychological scores in the HPV-positive group between the first two time-points, and among all three time-points. Analyses were carried out using SPSS v25, and p-value <0.05 was considered statistically significant.