Cervical cancer is highly preventable, and improving the screening consultation rate is therefore an urgent issue for the reduction of the prevalence of cervical cancer. We researched whether a self-collected HPV test was effective as a countermeasure for those who had not yet undergone the recommended cervical cancer screening. In this study, 12.6% of individuals who were initially referred were tested, and 1.4% of those who were tested were able to undergo surgery for invasive cancer or precancerous lesions. Our findings revealed that the self-collected HPV test showed certain efficacy as a screening measure for evaluating those who had not yet undergone traditional cervical cancer screening. Those who had not undergone cervical cancer screening and presented with positive HPV findings were encouraged to undergo a closer examination at a designated hospital. Our results suggest that it may become an effective method in the future in Japan, where the screening rate is low and cervical cancer is on the rise.
In Japan, the rate of cervical cancer screening is low and the active recommendation for vaccination against cervical cancer has been suspended for some time [2]. Therefore, improving the rate of cervical cancer screening is a critically important public health issue. We conducted this study because self-collected HPV tests have already been introduced and shown to be effective in these countries. Moreover, we thought that this intervention would be effective in guiding women at a high risk of HPV positivity (rather than recommending traditional cytopathological examinations to the unexamined patients).
We conclude that HPV testing using self-collected samples is a convenient and effective means for improving the cervical cancer screening rate. However, to serve as an alternative cervical cancer screening technique, this method must show a sensitivity equivalent to HPV testing using physician-collected cervical samples.
We previously reported that results were consistent between physician- and self-collected samples and that the agreement rate was especially high for HPV types 16 and 18 (as measured using κ-values) [9]. Among women presenting with CIN3, when a positive physician-collected sample was considered a true positive, the sensitivity and specificity of self-collected samples were 100% and 100% for HPV type 16, 75% and 100% for HPV type 18, and 92.0% and 96.3% for the other HPV types, respectively [9].
Onuma et al. reported that HPV self-sampling results showed good agreement with physician sampling results and that the sensitivity of CIN2 detection by self-sampling was as high as that of physician sampling [10]. Ngu et al. likewise reported that the concordance for HPV detection between self-sampled and clinician-sampled specimens was 90.2% (95% confidence interval [CI]: 85.1–93.8%; Cohen’s kappa 0.59 [95% CI: 0.42–0.75]) in Hong Kong. These researchers conclude that HPV self-sampling is an effective method for cervical cancer screening and can be considered an effective screening option, especially in women who are reluctant or unable to attend regular screenings [11].
In addition, Saville et al. reported that HPV16/18 results showed high observed agreement between self- and practitioner-collected samples in all assays (range: 0.94–0.99), with good agreement for non-HPV16/18 oncogenic HPV types (range: 0.64–0.73). These researchers concluded that self-collection showed good concordance and sensitivity for HPV-based cervical screening compared to those for practitioner-collected samples in assays conducted within the Australian National Cervical Screening Program [12]. These results indicate that self-administered HPV tests may be a viable option for cervical cancer screening.
Several studies have reported that self-collected HPV tests have led to an increase in the consultation rates [13–16]. For example, in a study conducted in Sweden, Sanner et al. reported that 63% of the women invited to participate in their study (i.e., those who did not have a screening record within the previous 6 years) requested a self-testing kit and that 39% of these women sent a self-sampling kit to the designated laboratory [13]. In another study conducted in Copenhagen, Denmark, Lam et al. reported that 32% of the recruited women who were not screened in the previous 4–6 years requested self-sampling kits and that 20% sent a self-sampling kit to the designated laboratory [14].
Moreover, Arbyn et al. examined the acceptance rate of self-collecting HPV tests in a randomized controlled trial [15]. The mean percentage of women in the self-sampling arm with an HPV test conducted on a self-sample after the research team mailed a self-sampling kit to the participant’s home in a “mail-to-all” campaign was 19.2% (95% CI: 15.7–23.0%) [15]. The pooled participation rate was 7.8% (95% CI: 5.2–10.9%) when women had to request a self-sampling kit (i.e., opt-in) [15]. The pooled percentage of participating women in the intention-to-treat analysis within the self-sampling arm was 17.7% (12.3–23.9%) in the opt-in scenario [15]. These researchers concluded that offering self-sampling kits was generally more effective in reaching under-screened women than sending invitations. Moreover, these researchers reported follow-up compliance rates for HPV-positive individuals in a meta-analysis evaluating a self-collected HPV testing intervention, with a consultation rate of 70.4% (95% CI: 58.3–81.3%) in reference to cytological triage [15]. The corresponding consultation rate in our study was 79.8%, which was higher than that of the prior meta-analysis. The high consultation rate in our study may be due to our designating a hospital for follow-up visitation and testing.
The detection rate for a presentation of CIN2 or higher was as high as 18.3% on cytology triage of the HPV-positive individuals enrolled in this study. When screening using cytology alone, the detection rate for a presentation of CIN2 or higher was reported as approximately 4.4% in the literature [17]. The corresponding detection rate was higher in the present study. However, our study found two cases of invasive gynecologic cancer, whereas no cervical cancer patients were diagnosed within the standard cervical cancer screening performed in Muroran City during the same time period. This study confirmed that the HPV-positive cases who had not undergone cervical cancer screening were at high risk for cervical cancer.
The limitations of this study are as follows. First, it is currently unclear which ages should be recommended for completing self-administered HPV kits. For example, there is currently no clear consensus as to whether women over the age of 20 years should be contacted or if the targeted age group should be those over the age of 30 years. Moreover, the upper age limit for this intervention is, likewise, presently unclear. Including women of younger age may lead to the detection of transient HPV infections as well as presenting a cause of unnecessary anxiety. In fact, our study revealed that the rate of being diagnosed with a finding of CIN2 or higher was statistically significantly lower in those in their 20s given positive HPV findings. However, to widely recommend medical examinations to the unvaccinated generation, it is necessary to inform the younger generation of this critically important public health concern and initiative.
Second limitation is an unclear optimal subsequent follow-up period for women who are found to be HPV-positive. Although it is sufficient for the participants to visit the hospital regularly following the detection of positive HPV findings, there is a possibility that a woman will elect not to undergo examinations. Therefore, effectively managing post-testing follow-up is of critical importance. Moreover, the specific testing that should be provided to individuals have been diagnosed as HPV-positive is presently unclear. Options include colposcopy as well as cytology prior to colposcopy. It may be possible to triage testing strategies according to HPV type. For example, while colposcopy may be performed for HPV type 16, it may be possible to evaluate cytology prior to performing colposcopy for other HPV types.
Third limitation is that this study included women who were not truly unexamined (i.e., who had been examined for HPV/cervical cancer more than 5 years prior as well as those who had undergone screenings elsewhere). We conclude that it is necessary to evaluate the status of the city's medical examination system in the future. It is also necessary to publicize the reliability of the evaluated screening intervention, as some citizens may not have participated in this study because they did not trust the self-collected HPV testing method.
Fourth limitation is that we conducted an opt-in study. It may be preferable to send the kit only to those who request it, send the kit to all the unexamined people, or distribute a coupon for testing at the city facility. This remains to be elucidated in future studies. Two previous meta-analyses revealed that sending self-collection kits directly to the participants’ home address generated a higher response rate than sending an invitation letter [18, 19]. How to best send self-collection kits to at-risk citizens is a critical issue to resolve within future investigations.
The strength of this study is that many of the patients who had not been examined had an opportunity to visit the hospital and that several patients successfully underwent treatment for cervical cancer or precancerous lesions through surgery. This strategy should be useful for health management in the future because most participants continue to follow through after undergoing the test.