Abstract
Objective
To evaluate the impact of healthcare reorganization during the severe acute respiratory syndrome coronavirus 2 pandemic on Italian colposcopy clinic activities, focusing on cervical excision procedures, follow-ups for conservative management of low-grade lesions, and follow-ups post cervical excision.
Methods
Retrospective study conducted in 14 Italian colposcopy clinics. The number and clinical characteristics of cervical excisions, follow-ups for conservative management of low-grade lesions, and follow-ups after cervical excision were compared between the period March 1, 2019 to February 29, 2020 (pre-pandemic) and March 1, 2020 to February 28, 2021 (pandemic) with a Poisson regression analysis.
Results
In the pandemic period, the number of cervical excisions was reduced by 8.8% (95% confidence interval [CI]=−15.6% to −2%; p=0.011). Excisions were less frequently performed in the operating room (−35.1%; 95% CI=−47.6% to −22.6%; p<0.001), the number of patients from spontaneous screening was reduced by −14.0% (95% CI=−23.4% to −4.6%; p=0.003), and the CO2-laser technique was used less frequently (−30%; 95% CI=−45.1% to −15.0%; p<0.001). As compared to the pre-pandemic period, the number of follow-ups for conservative management of low-grade lesions was reduced by −26.7% (95% CI=−39.0% to −14.4%; p<0.001), and the follow-up appointments after cervical excision were reduced by −51.0% (95% CI=−58.1% to −43.9%; p<0.001).
Conclusion
The most significant impact of the healthcare reorganization during the coronavirus disease 2019 pandemic was on follow-ups after cervical excision. The resumption of disrupted activities should follow a risk-based prioritization, starting from women in follow-up after cervical excision. It is advisable that the trend of performing cervical excision as an outpatient procedure is maintained in the post-pandemic period.
Keywords: Colposcopy, Cervical Cancer, COVID-19 Pandemic, Conization, Screening
Synopsis
Follow-ups after cervical excisions were highly impacted during the pandemic. Cervical excisions and follow-ups for low-grade lesions maintained an acceptable rate. The resumption of activities should be prioritized according to individual risk. The trend of performing cervical excision in outpatient should be maintained.
INTRODUCTION
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has radically changed the organization of health systems worldwide. One of the main aims of public health during the coronavirus disease 2019 (COVID-19) pandemic was to reduce the impact on healthcare systems. In Italy, in the first phase of the pandemic (starting from March 16, 2020), all outpatient services have been postponed [1], including the HPV vaccination program, cervical cancer screening, colposcopy clinic activities, and outpatient surgery of the lower genital tract, except for cases which required urgent evaluation [1]. These decisions had an impact on a large percentage of the Italian population, considering that the HPV vaccination coverage on December 31, 2019 ranged from 41.6% to 70.4% for women aged 12–23 years and that the Italian cervical cancer screening coverage was 79.9% (48.7% organized screening and 30.8% spontaneous screening) in the period 2016–2019 [2,3]. In this context, scientific societies have provided guidance to advise clinicians and service providers on how to triage patients who needed a prompt evaluation in a colposcopy clinic from patients whose care could be safely postponed [2,3]. After the intensive adoption of preventive measures for SARS-CoV-2 diffusion, the consequent reduction in the incidence of new cases, and the improvement of the health facilities organization, the Italian Ministry of Health has provided new indications on how to resume disrupted activities during the first months of the pandemic [4]. The recommendations published on June 1, 2020, offered the possibility of a progressive reactivation of the outpatient services, with a particular interest in cancer screening programs [4]. The resumption of disrupted activities took place unevenly, considering the different pressure on the health systems in different regions and the increase in new cases in the last months of the year 2020 [5]. In May 2021, almost all Italian regions resumed outpatient services and screening programs.
This interruption of preventive strategies may have increased the time between an abnormal first-level test result and the following diagnostic tests. It may have caused the patients to miss follow-up appointments or delay urgent evaluation for symptoms suggestive of lower genital tract malignancies, with a potential lack of diagnosis and treatment of cervical cancer and its precursors.
As a matter of fact, in California, cervical cancer screening rates for 21–65 years old women dropped in 2020 after stay-at-home orders. After lifting the order, they remain lower than the corresponding 2019 months [6].
Predictive models have shown that COVID-19 related disruptions of cervical cancer prevention activities would increase cervical cancer cases by 2027 [7,8]. It is also reported that this increase will be primarily due to disruption of excisional treatment and follow-up appointments (colposcopy clinics activities), rather than delays in first-level screening, which will probably have a negligible effect on cervical cancer diagnosis [7,8].
Therefore, this study aims to evaluate the impact of healthcare reorganization during the SARS-CoV-2 pandemic on Italian colposcopy clinic activities by comparing the volume of activity of the 12 months before the pandemic with the first 12 months of the pandemic spread in Italy, focusing on cervical excision procedures, follow-ups for conservative management of low-grade lesions, and follow-ups post cervical excision.
MATERIALS AND METHODS
This retrospective study was conducted in 14 Italian colposcopy clinics, including 3 categories of patients: those subjected to cervical excision procedure, those in follow-up for conservative management of low-grade lesions, and those in follow-up after cervical excision in the period March 1, 2019 to February 29, 2020 (pre-pandemic period), and March 1, 2020 to February 28, 2021 (pandemic period).
Patients were considered as eligible in case of cervical excision procedure performed in the period March 1, 2019 to February 29, 2020, or March 1, 2020 to February 28, 2021, or last follow-up appointment for conservative management of low-grade lesions performed in the period March 1, 2019 to February 29, 2020, or March 1, 2020 to February 28, 2021, or last follow-up appointment after cervical excision performed in the period March 1, 2019 to February 29, 2020, or March 1, 2020 to February 28, 2021. Patients were exluded in case of missing data.
Cervical excisions were performed for the following indications: histopathological diagnosis at a cervical biopsy of high-grade cervical intraepithelial lesion (high-grade squamous intraepithelial lesion [HSIL]-cervical intraepithelial neoplasia [CIN]2 or HSIL-CIN3), histopathological diagnosis at a cervical biopsy of persistent (more than 2 years) low-grade cervical intraepithelial lesion (low-grade squamous intraepithelial lesion [LSIL]-CIN1), histopathological diagnosis at a cervical biopsy of LSIL-CIN1 in post-menopausal women with not-visible squamocolumnar junction, histopathological diagnosis at a cervical biopsy of adenocarcinoma in situ (AIS), or major colposcopic abnormalities with high-grade cervical cytology (see and treat approach). Regarding cervical excision procedures, the following variables were collected and compared between the 2 periods: the total number of cervical excisions performed in each institution; the total number of operators that performed the excisions; patient’s age (≤24, 25–34, 35–44, 45–54, 55–64, and ≥65 years); the approach to cervical excision (2-step approach with cervical biopsy and subsequent excision or see and treat approach); the surgical technique (loop electrosurgical excisional procedure [LEEP], CO2-laser, or cold-knife); the setting (outpatient vs. operating room); the screening modality (organized vs. spontaneous); the time between the excision and the screening test (high-risk human papillomavirus [HR-HPV] test, cervical cytology or both), collected as within the 3 or 6 months following the screening test or later; colposcopy (number of excisions with at least one previous colposcopy and number of excisions performed under colposcopic guidance); the time between the excision and the cervical biopsy, collected as within 1 or 3 months following the cervical biopsy or later; the definitive histology of the cone specimen; the margin status (negative, positive ectocervical, positive endocervical, both positive, or not assessable).
Follow-up appointments for conservative management (without cervical excision or destructive treatment) of low-grade cervical lesions (previous histopathological diagnosis of LSIL-CIN1) were scheduled as follows: execution of cervical cytology and HR-HPV test at 12 and 24 months from diagnosis, with possible execution of colposcopy and cervical biopsy in case of positivity of one of the 2 tests. The activities regarding follow-up after conservative management of low-grade lesions were assessed by collecting the number of follow-up appointments performed in each institution, the number of negative follow-ups, the number of “low-grade” positive follow-ups (defined as a result of low-grade cytology, low-grade histology, or HR-HPV positivity during follow-up), the number of “high-grade” positive follow-ups (defined as a result of high-grade cytology, high-grade histology, or AIS during follow-up), and the number of follow-ups with an invasive cancer diagnosis.
Follow-up appointments after cervical excisional treatment were scheduled as follows: execution of cervical cytology, HR-HPV test, and colposcopy at 6 months from the procedure, with possible execution of cervical biopsy in case of evidence of colposcopic abnormalities. At 18 months from the procedure, cervical cytology and HR-HPV test were performed, with colposcopy in case of positivity of one or both tests. During pandemic period, telephonic follow-ups were not performed in the included institutions. The activities regarding follow-up after cervical excision were evaluated by collecting the number of follow-up appointments performed in each institution, the number of negative follow-ups, the number of “low-grade” positive follow-ups (defined as a result of low-grade cytology, low-grade histology, or HR-HPV positivity during follow-up), the number of “high-grade” positive follow-ups (defined as a result of high-grade cytology, high-grade histology, or AIS during follow-up), and the number of follow-ups with an invasive cancer diagnosis.
The primary outcomes were: the total number of cervical excisions performed in the included institutions in the 2 periods (pre-pandemic and pandemic); the total number of follow-up appointments for conservative management of low-grade cervical lesions performed in the included institutions in the 2 periods; the total number of follow-up appointments after cervical excisional treatment performed in the included institutions in the 2 periods.
1. Number of subjects and study size
The sample size for the present study was determined for the 3 primary outcomes. The G*Power version 3.1.9 software was used to determine the required sample size for the 2-tailed Poisson regression (test family: z-tests) that was used to compare the total number of cervical excisions performed, the total number of follow-up appointments for conservative management of low-grade cervical lesions, and the total number of follow-up appointments after cervical excisional treatment between the pre-pandemic and pandemic period, with an expected decrease (Expβ1) of 0.95, an α of 0.01, a power of 0.99, a mean exposure of 1 year, a binomial X distribution, a X parm ∏ of 0.5, and 3 different base rates (Expβ0) according to the 3 primary outcomes. The base rates (Expβ0) were determined considering the following estimates: 130 cervical excisions per year for each institution, 200 follow-up appointments for conservative management of low-grade cervical lesions per year for each institution, and 170 follow-up appointments after cervical excisional treatment per year for each institution.
Considering the parameters described above, a total sample size of 1,518 cervical excisions per year, 987 follow-up appointments for conservative management of low-grade cervical lesions per year, and 1,161 follow-up appointments after cervical excisional treatment per year were required.
2. Statistical analysis
The statistical software used was SPSS 27.0 (SPSS Inc., Chicago, IL, USA). The normality of each variable was evaluated by the Shapiro-Wilk test. Normally distributed variables were reported as arithmetic mean±standard deviation (SD), while not-normally distributed variables were reported as median and interquartile range (IQR). Qualitative variables were reported as numbers and percentages.
The comparison of the variables between the pre-pandemic and pandemic period was performed by running a Poisson regression analysis, considering as dichotomous predictor the pre-pandemic/pandemic period. The assumptions of independence of observations, Poisson distribution of counts, and equidispersion of the model were checked. Results were reported considering the coefficient estimates of the Poisson regression (B), with the 95% confidence interval (CI). A p-value <0.05 was regarded as statistically significant.
According to Italian legislation, the local ethical committee of the coordinator center (Comitato Etico Regionale Marche) took notice of the study protocol (No. CERM 2022/9). The manuscript was prepared according to STROBE checklist for reporting observational studies.
RESULTS
In the period March 1, 2019 to February 29, 2020 (pre-pandemic period), a total of 1,745 cervical excisions were performed in the 14 included colposcopy clinics, with a mean±SD number of cervical excisions per center of 125±66 and a median (IQR) number of operators per center of 3 (2–5). In the same 14 colposcopy clinics, 1,598 cervical excisions were performed in the period March 1, 2020 to February 28, 2021 (pandemic period), with a mean±SD number of cervical excisions per center of 114±73 and a median (IQR) number of operators per center of 3 (2–5).
A reduction between the number of excisions in the pre-pandemic and the pandemic period of −8.8% (95% CI=−15.6% to −2%; p=0.011) was evidenced. Table 1 reports the comparison of the cervical excisions’ characteristics between the pre-pandemic and pandemic period. Cervical excisions were less frequently performed in the operating room (−35.1%; 95% CI=−47.6% to −22.6%; p<0.001) during the pandemic period. CO2-laser technique was used less frequently (−30%; 95% CI=−45.1% to −15.0%, p<0.001). The number of patients from spontaneous screening was reduced by −14.0% (95% CI=−23.4% to −4.6%; p=0.003). A lower number of cervical excisions performed within 6 months after the screening tests emerged during the pandemic (−17.3%; 95% CI=−31.3% to −3.3%; p=0.016), as well as a lower number of cervical excisions performed more than 3 months after the screening tests (−17.2%; 95% CI=−33.4% to −1.1%; p=0.036). In patients in whom a see & treat approach was not performed, the median (IQR) period in months between the cervical biopsy and the excision was 2 (1–2) months in the pre-pandemic period and 2 (1–3) months in the pandemic period (p<0.001). A lower number of HSIL-CIN3 (−18.2%; 95% CI=−28.8% to −7.7%; p=0.001), squamous cervical cancer pT1a1 – International Federation of Gynecology and Obstetrics (FIGO) Ia1 (−43.4%; 95% CI=−399.3% to −0.8%; p=0.046), and squamous cervical cancer higher than pT1a1 – FIGO Ia1 (−53.9%; 95% CI=−107.7% to −0.1%; p=0.050) definitive histologies was noted in the pandemic period.
Table 1. Comparison of cervical excisions characteristics between the pre-pandemic and pandemic period (Poisson regression analysis).
| Characteristic | Pre-pandemic | Pandemic | Variation (%) | 95% CI (%) | p-value | ||
|---|---|---|---|---|---|---|---|
| Lower limits | Upper limits | ||||||
| Total number of cervical excisions | 1,745 | 1,598 | −8.8 | −15.6 | −2.0 | 0.011 | |
| Age (yr) | |||||||
| ≤24 | 19 | 14 | −30.5 | −99.6 | 38.5 | 0.386 | |
| 25–34 | 542 | 464 | −15.5 | −27.9 | −3.1 | 0.014 | |
| 35–44 | 591 | 580 | −1.9 | −13.3 | 9.6 | 0.748 | |
| 45–54 | 363 | 335 | −8.0 | −22.9 | 6.8 | 0.289 | |
| 55–64 | 181 | 155 | 15.5 | −37.0 | 5.9 | 0.156 | |
| ≥65 | 49 | 50 | 2.0 | −37.4 | 41.4 | 0.920 | |
| Approach | |||||||
| Two-step approach (cervical biopsy + subsequent excision) | 1,410 | 1,304 | −7.8 | −15.3 | −0.3 | 0.042 | |
| See and treat | 335 | 294 | −13.1 | −28.7 | 2.6 | 0.102 | |
| Surgical technique | |||||||
| LEEP | 1,336 | 1,299 | −2.8 | −10.4 | 4.8 | 0.471 | |
| CO2-laser | 397 | 294 | −30.0 | −45.1 | −15.0 | <0.001 | |
| Cold knife | 12 | 5 | −87.5 | −191.9 | 16.8 | 0.100 | |
| Setting | |||||||
| Outpatient setting | 1,147 | 1,177 | 2.6 | −5.6 | 10.7 | 0.534 | |
| Operating room | 598 | 421 | −35.1 | −47.6 | −22.6 | <0.001 | |
| Screening modality | |||||||
| Organized screening | 813 | 788 | −3.1 | −12.9 | 6.7 | 0.532 | |
| Spontaneous screening | 932 | 810 | −14.0 | −23.4 | −4.6 | 0.003 | |
| Cervical excision performed | |||||||
| Within the 3 months after the screening tests | 1,171 | 1,067 | −9.3 | −17.6 | −1.0 | 0.028 | |
| Within the 6 months after the screening tests | 429 | 361 | −17.3 | −31.3 | −3.3 | 0.016 | |
| More than 6 months after the screening tests | 145 | 170 | 15.9 | −6.2 | 38.1 | 0.159 | |
| Colposcopy | |||||||
| Excisions with at least one previous colposcopy | 1,738 | 1,586 | −9.2 | −16.0 | −2.3 | 0.008 | |
| Excisions performed under colposcopic guidance | 1,700 | 1,560 | −8.6 | −15.5 | −1.7 | 0.014 | |
| Cervical excision performed | |||||||
| See & treat approach | 335 | 294 | −13.1 | 28.7 | 2.6 | 0.102 | |
| Within 1 month after the cervical biopsy | 411 | 382 | −7.3 | −106.0 | 6.6 | 0.303 | |
| Within the 3 months after the cervical biopsy | 677 | 651 | −3.9 | −50.9 | 6.8 | 0.476 | |
| More than 3 months after the cervical biopsy | 322 | 271 | −17.2 | −33.4 | −1.1 | 0.036 | |
| Definitive histology after cervical excision | |||||||
| Negative | 94 | 108 | 13.9 | −13.8 | 41.5 | 0.325 | |
| LSIL (CIN1) | 233 | 233 | 0 | −18.2 | 18.2 | 1.000 | |
| HSIL (CIN2) | 508 | 521 | 2.5 | −9.7 | 14.7 | 0.685 | |
| HSIL (CIN3) | 762 | 635 | −18.2 | −28.8 | −7.7 | 0.001 | |
| Squamous cervical cancer (pT1a1 – FIGO Ia1) | 54 | 35 | −43.4 | −399.3 | −0.8 | 0.046 | |
| Squamous cervical cancer (higher than pT1a1 – FIGO Ia1) | 36 | 21 | −53.9 | −107.7 | −0.1 | 0.050 | |
| AIS | 25 | 21 | −17.4 | −75.5 | 40.6 | 0.556 | |
| Adenocarcinoma (pT1a1 – FIGO Ia1) | 12 | 9 | −28.8 | −115.2 | 57.7 | 0.514 | |
| Adenocarcinoma (higher than pT1a1 – FIGO Ia1) | 7 | 12 | 53.9 | −128.4 | 147.1 | 0.257 | |
| Concomitant high-grade squamous and glandular lesion | 5 | 1 | −160.9 | −375.6 | 53.8 | 0.142 | |
| Other definitive histology | 9 | 2 | −150.4 | −303.6 | 2.8 | 0.054 | |
| Excision margins | |||||||
| Negative margins | 1,286 | 1,114 | −14.4 | −22.4 | −6.3 | <0.001 | |
| Positive ectocervical margin | 167 | 225 | 29.8 | 9.8 | 49.8 | 0.004 | |
| Positive endocervical margin | 162 | 143 | −12.5 | −35.0 | 10.0 | 0.277 | |
| Positive ectocervical and endocervical margin | 91 | 63 | −36.8 | −68.9 | −4.6 | 0.025 | |
| Not assessable | 39 | 53 | 30.7 | −10.7 | 72.0 | 0.146 | |
Variation (%) = coefficient estimates of the Poisson regression (B) (%).
AIS, adenocarcinoma in situ; CI, confidence interval; CIN, cervical intraepithelial neoplasia; HSIL, high-grade squamous intraepithelial lesion; LEEP, loop electrosurgical excisional procedure; LSIL, low-grade squamous intraepithelial lesion; FIGO, International Federation of Gynecology and Obstetrics.
The number of follow-up appointments for conservative management of low-grade lesions was reduced by −26.7% (95% CI=−39.0% to −14.4%; p<0.001) during the pandemic period. Table 2 reports the comparison of follow-up outcomes for conservative management of low-grade lesions between the pre-pandemic and pandemic periods. The number of negative follow-ups was reduced in the pandemic period (−45.4%; 95% CI=−62.8% to −28.0%; p<0.001), with a lower number of high-grade lesion/AIS (−167.4%; 95% CI=−707.9% to −44.1%; p=0.008).
Table 2. Comparison of follow-up for conservative management of low-grade lesions outcomes between pre-pandemic and pandemic period (Poisson regression analysis).
| Outcome | Pre-pandemic | Pandemic | Variation (%) | 95% CI (%) | p-value | ||
|---|---|---|---|---|---|---|---|
| Lower limits | Upper limits | ||||||
| Number of follow-up for conservative management of low-grade lesions | 585 | 448 | −26.7 | −39.0 | −14.4 | <0.001 | |
| Negative | 326 | 207 | −45.4 | −62.8 | −28.0 | <0.001 | |
| Low-grade lesion or HR-HPV-positivity | 238 | 237 | −4.0 | −18.4 | 17.6 | 0.963 | |
| High-grade lesion or AIS | 16 | 3 | −167.4 | −707.9 | −44.1 | 0.008 | |
| Invasive | 5 | 1 | −160.9 | −375.6 | 53.8 | 0.142 | |
Variation (%) = coefficient estimates of the Poisson regression (B) (%).
AIS, adenocarcinoma in situ; CI, confidence interval; HR-HPV, high-risk human papillomavirus.
A reduction of −51.0% (95% CI=−58.1% to −43.9%; p<0.001) in the number of follow-up appointments after cervical excision during the pandemic emerged. The reduction was more evident for high-grade lesion/AIS (−76.8%; 95% CI=−112.2% to −41.5%; p<0.001) than for the negative and CIN1 findings (Table 3).
Table 3. Comparison of follow-up after cervical excision outcomes between pre-pandemic and pandemic period (Poisson regression analysis).
| Outcome | Pre-pandemic | Pandemic | Variation (%) | 95% CI (%) | p-value | ||
|---|---|---|---|---|---|---|---|
| Lower limits | Upper limits | ||||||
| Number of follow-ups after cervical excision | 2,055 | 1,234 | −51.0 | −58.1 | −43.9 | <0.001 | |
| Negative | 1,553 | 946 | −49.6 | −57.7 | −41.5 | <0.001 | |
| Low-grade lesion or HR-HPV-positivity | 394 | 239 | −50.0 | −66.1 | −33.9 | <0.001 | |
| High-grade lesion or AIS | 97 | 45 | −76.8 | −112.2 | −41.5 | <0.001 | |
| Invasive | 11 | 4 | −101.2 | −215.6 | 13.3 | 0.083 | |
Variation (%) = coefficient estimates of the Poisson regression (B) (%).
AIS, adenocarcinoma in situ; CI, confidence interval; HR-HPV, high-risk human papillomavirus.
DISCUSSION
The analysis of data from the present study has shown a −8.8% reduction in the number of cervical excisions performed in the 14 included colposcopy clinics in the pandemic period (March 1, 2020 to February 28, 2021). Follow-up appointments have also undergone a reduction during the pandemic period, with a percentage reduction of −26.7% for follow-up appointments for conservative management of low-grade lesions and −51.0% for follow-up appointments post-cervical excision.
The differences in the activities of the colposcopy clinics between the 2 periods can be mainly explained by the reorganization of the Italian healthcare system due to the adoption of preventive measures for SARS-CoV-2 diffusion and the need to reduce the impact on the workload of healthcare facilities.
This reorganization seems to have had a limited (−8.8%) impact on the number of cervical excisions performed in the included colposcopy clinics, probably because indications to excisional treatment were among those considered as “not-postponable” and which had to be guaranteed within 3 months at the latest [2,3]. This condition made it possible to keep secondary prevention of cervical cancer active during the pandemic period, maintaining diagnosis and treatment of high-grade intraepithelial lesions and invasive lesions to a volume of activity comparable to that of the pre-pandemic period. A similar reduction trend was identified in the study by Ivanuš et al. [9] of 2021, who reported that cervical treatments were around 10% below the reference value during the pandemic.
Cervical excisions procedures were less frequently performed in the operating room (−35.1%), while the number of outpatient procedures did not differ between the 2 periods. This was an expected result since inpatient operating rooms were mainly reserved for surgical emergencies or major interventions for oncological indications or were converted into intensive care beds. Moreover, a large number of anesthetists (who are needed for operating room procedures) were assigned to care for COVID patients in intensive care units (ICUs). It is desirable that this trend should be maintained, considering that outpatient procedures are comparable in efficacy and safety to inpatient procedures [10], require only local analgesia, reduce the length of stay, and have less impact on the healthcare facility. The 2021 European consensus statement on essential colposcopy has also indicated that local treatments should be performed, wherever possible, in outpatients and with local analgesia [11].
The analysis of data about the screening modality showed that the spontaneous screening was more affected by the reduction of activities than organized screening; this may have been linked to the fact that organized screening activities are entirely managed by the public health system, which could have resumed its activities earlier than other healthcare facilities where spontaneous screening can be performed.
During the pandemic period, we observed a higher reduction (−17.3%) in the number of cervical excisions performed within the 6 months after the screening test with respect to the number of cervical excisions performed within the 3 months after the screening test (−9.3%), and no difference in the number of cervical excisions performed more than the 6 months after the screening test. These differences can be interpreted as a delay in accessing second-level diagnostic and therapeutic procedures. However, the reduction was lower than that reported in the literature: Meggetto et al. [12] reported that 29.2% of patients with high-grade cytology waited more than 6 months for a colposcopy during the pandemic in Ontario, Canada.
The higher number of positive ectocervical in the pandemic period was an unexpected result, which cannot be fully explained by the available data and solid conclusions cannot be drawn.
The effect of colposcopic clinic activities disruption was even more evident when comparing the number of follow-up appointments after cervical excision between the pre-pandemic and pandemic period, which showed a decrease of −51.0%. This reduction could have had a significant impact on the efficacy of cervical cancer prevention, leading to missed diagnosis of both high-grade and invasive lesions in high-risk women, such as those in post-cervical excision follow-up.
Regarding the performed follow-ups, the comparison of outcomes showed a similar pattern to that observed in treatment with a larger reduction in the pandemic period, compared to the pre-pandemic period, of the most severe lesions (Table 2).
The most significant impact on the activities of Italian colposcopy clinics seems to have been on post-treatment follow-ups rather than cervical excisions or follow-ups for conservative management of low-grade lesions. In this context, the main challenge of the post-pandemic period will be the reintroduction of cervical cancer prevention services [13,14], and numerous factors will need to be taken into consideration: changes in resource availability, changes in women’s willingness to undergo screening, the need for social distancing, and the need for additional time for healthcare services [13,14]. The resolution of the backlog of disrupted services cannot rely solely on expanding service capacity with a generic re-calling of women who have not been screened, but it should first focus on high-risk women [8,13,14]. The level of risk can be defined by age, previous screen history, HPV vaccination status, smoking habit, immunosuppression, economic status, or geographical location [13,14]. Our results suggest that women in follow-up after excisional treatment should be re-called first since they experienced the most significant reduction of services during the pandemic. Risk-based prioritization, starting from women needing excisional treatment, colposcopy, or surveillance, allows to include a smaller number of women, which could have a more significant effect on the number of cervical cancer cases prevented [8].
An implementation for national cervical cancer screening services that may allow to reduce the number of accesses to healthcare facilities and COVID-19 transmission is HPV self-sampling, that should be promoted during disruption periods [3].
This study is strengthened by the large number of included cases from 14 colposcopy clinics distributed throughout the Italian national territory. One of the limitations is that we cannot exclude those factors other than the COVID-19 pandemic that can explain the highlighted differences; however, the only substantial changes in colposcopy clinics organization during the considered periods were those related to COVID-19 and, therefore, this bias may have a limited impact on the results. Moreover, since the included centers are a national reference for the pathology, we cannot rule out if the patients preferred to carry out the control exams close to their homes in a context of limited national travel due to the COVID-19 pandemic. Furthermore, in some geographic areas, urgent oncologic patients were referred to covid-free hospitals, usually oncological centers, while most of the participating centers in our study are multispecialty facilities. It is not possible from our data to distinguish between patients who missed their appointments due to COVID-19 positivity or due to healthcare services disruption.
In conclusion, the reorganization of healthcare services during the COVID-19 pandemic seems to have had the most significant impact on follow-ups after cervical excision, while cervical excision procedures and follow-ups for conservative management of low-grade lesions were less impacted. It is advisable that the trend of performing cervical excision as an outpatient procedure also continue in the post-pandemic period. The resumption of disrupted activities should follow a risk-based prioritization, starting from women in follow-up after cervical excision and maybe in those where a previous screen history is missing. Each clinic should define a list of patients from the highest to the lowest risk to organize re-calling of missed patients. Collecting data about the volume of activities in the post-pandemic period should also be a priority to monitor the resumption of cervical cancer prevention and verify the recovery of high-risk patients.
Footnotes
Conflict of Interest: No potential conflict of interest relevant to this article was reported.
- Conceptualization: D.C.G., G.R.P., C.A.
- Data curation: G.L., D.G.J., C.N., S.F., B.M., B.G., D.V.R., O.M., C.F., G.B., D.M., M.E., L.C.A., V.A., P.A., A.A., A.C., A.M., C.P., P.A., S.G.
- Formal analysis: D.C.G., G.R.P., D.G.J., C.N., S.F., B.M., B.G., D.V.R., O.M., C.F., G.B., D.M., M.E., L.C.A., V.A., P.A., A.A., A.C., A.M., C.P., P.A., S.G.
- Investigation: D.C.G., G.L., D.G.J., C.N., S.F., B.M., B.G., D.V.R., O.M., C.F., G.B., D.M., M.E., L.C.A., V.A., P.A., A.A., A.C., A.M., C.P., P.A., S.G.
- Methodology: G.R.P., G.L., D.G.J., C.A.
- Project administration: C.A.
- Supervision: C.A.
- Writing - original draft: D.C.G.
- Writing - review & editing: G.R.P., C.A.
References
- 1.Italian Ministry of Health. Guidelines for remodeling of the deferrable planned activity during COVID-19 emergency [Internet] Roma: Italian Ministry of Health; 2020. [cited 2022 Mar 16]. Available from: https://www.trovanorme.salute.gov.it/norme/renderNormsanPdf?anno=2020&codLeg=73675&parte=1%20&serie=null . [Google Scholar]
- 2.Ciavattini A, Delli Carpini G, Giannella L, De Vincenzo R, Frega A, Cattani P, et al. Expert consensus from the Italian Society for Colposcopy and Cervico-Vaginal Pathology (SICPCV) for colposcopy and outpatient surgery of the lower genital tract during the COVID-19 pandemic. Int J Gynaecol Obstet. 2020;149:269–272. doi: 10.1002/ijgo.13158. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Ciavattini A, Delli Carpini G, Giannella L, Arbyn M, Kyrgiou M, Joura EA, et al. European Federation for Colposcopy (EFC) and European Society of Gynaecological Oncology (ESGO) joint considerations about human papillomavirus (HPV) vaccination, screening programs, colposcopy, and surgery during and after the COVID-19 pandemic. Int J Gynecol Cancer. 2020;30:1097–1100. doi: 10.1136/ijgc-2020-001617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Italian Ministry of Health. Guidelines for progressive reactivation of Linee di indirizzo per la progressiva riattivazione of the planned activities considered deferrable during COVID-19 emergency [Internet] Roma: Italian Ministry of Health; 2020. [cited 2022 Mar 16]. Available from: https://www.trovanorme.salute.gov.it/norme/renderNormsanPdf?anno=2020&codLeg=77493&parte=1%20&serie=null . [Google Scholar]
- 5.Italian Ministry of Health. Organizational Guidelines for the management of the COVID-10 emergency in the current pandemic phase [Internet] Roma: Italian Ministry of Health; 2020. [cited 2022 Mar 16]. Available from: https://www.trovanorme.salute.gov.it/norme/renderNormsanPdf?anno=2020&codLeg=77493&parte=1%20&serie=null . [Google Scholar]
- 6.Miller MJ, Xu L, Qin J, Hahn EE, Ngo-Metzger Q, Mittman B, et al. Impact of COVID-19 on cervical cancer screening rates among women aged 21-65 years in a large integrated health care system - Southern California, January 1-September 30, 2019, and January 1-September 30, 2020. MMWR Morb Mortal Wkly Rep. 2021;70:109–113. doi: 10.15585/mmwr.mm7004a1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Wentzensen N, Clarke MA, Perkins RB. Impact of COVID-19 on cervical cancer screening: challenges and opportunities to improving resilience and reduce disparities. Prev Med. 2021;151:106596. doi: 10.1016/j.ypmed.2021.106596. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Burger EA, Jansen EE, Killen J, Kok IM, Smith MA, Sy S, et al. Impact of COVID-19-related care disruptions on cervical cancer screening in the United States. J Med Screen. 2021;28:213–216. doi: 10.1177/09691413211001097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Ivanuš U, Jerman T, Gašper Oblak U, Meglič L, Florjančič M, Strojan Fležar M, et al. The impact of the COVID-19 pandemic on organised cervical cancer screening: The first results of the Slovenian cervical screening programme and registry. Lancet Reg Health Eur. 2021;5:100101. doi: 10.1016/j.lanepe.2021.100101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Leimbacher B, Samartzis N, Imesch P, Dedes KJ, Fink D, Canonica C. Inpatient and outpatient loop electrosurgery excision procedure for cervical intraepithelial neoplasia: a retrospective analysis. Arch Gynecol Obstet. 2012;285:1441–1445. doi: 10.1007/s00404-011-2148-7. [DOI] [PubMed] [Google Scholar]
- 11.Redman CWE, Kesic V, Cruickshank ME, Gultekin M, Carcopino X, Castro Sanchez M, et al. European consensus statement on essential colposcopy. Eur J Obstet Gynecol Reprod Biol. 2021;256:57–62. doi: 10.1016/j.ejogrb.2020.06.029. [DOI] [PubMed] [Google Scholar]
- 12.Meggetto O, Jembere N, Gao J, Walker MJ, Rey M, Rabeneck L, et al. The impact of the COVID-19 pandemic on the Ontario Cervical Screening Program, colposcopy and treatment services in Ontario, Canada: a population-based study. BJOG. 2021;128:1503–1510. doi: 10.1111/1471-0528.16741. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Castanon A, Rebolj M, Burger EA, de Kok IM, Smith MA, Hanley SJ, et al. Cervical screening during the COVID-19 pandemic: optimising recovery strategies. Lancet Public Health. 2021;6:e522–e527. doi: 10.1016/S2468-2667(21)00078-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Castanon A, Rebolj M, Pesola F, Sasieni P. Recovery strategies following COVID-19 disruption to cervical cancer screening and their impact on excess diagnoses. Br J Cancer. 2021;124:1361–1365. doi: 10.1038/s41416-021-01275-3. [DOI] [PMC free article] [PubMed] [Google Scholar]