Abstract
Background/Aim: The global impact of the COVID-19 pandemic resulted in disruptions to healthcare systems throughout the world. The numbers of cytology examinations, human papillomavirus (HPV) tests, and women referred for colposcopy decreased in many countries. There have been no reports on cervical cancer screening in Germany. This study aimed to describe changes in the numbers of colposcopies, cytology examinations, HPV tests, and histological results during the pandemic compared to the pre-pandemic years in order to evaluate the impact of the COVID-19 pandemic on cervical cancer screening. Patients and Methods: The numbers of colposcopies, cytology examinations, HPV tests, and histologic results were analyzed retrospectively for the period January 2018 to December 2022. The 2 years period before the pandemic (2018 and 2019) were compared with the 3 years period of the pandemic (2020-2022). Results: In total, 6,518 colposcopies were performed in 5,579 women. The numbers of colposcopies, cytology examinations, and high-risk HPV (hrHPV) tests increased during the pandemic years. The number of biopsies per year taken was stable (range=450-554). The relative numbers of cervical intraepithelial neoplasia (CIN) III/HSIL findings were stable, while the numbers of cervical cancers identified increased slightly from 15 (6.6%) in 2018 to 22 (7.4%) in 2022. Conclusion: Increases in numbers of women examined and colposcopies were observed in the years 2021 and 2022 during the pandemic, in comparison to the preceding years. These also led to increases in the figures for cytology, hrHPV, histology, and operations. The onset of the pandemic occurred in the same year as a newly organized screening program started in Germany. The increases might therefore be due to the newly organized screening system.
- High-grade squamous intraepithelial lesion (HSIL)
- cervical dysplasia
- cervical cancer
- COVID-19 pandemic
- cervical cancer screening
Cervical cancer (CC) is one of the most common cancers amongst women worldwide (1-5). High-grade squamous lesions (HSILs) and CC are caused by persistent infection with human papillomavirus (HPV) (6). The detection of HSIL is essential, since HSIL is able to progress to CC (7). Since the introduction of a nationwide screening program in Germany in 1971, the incidence and mortality of CC have been declining over three decades (8-11). In January 2020, a newly organized screening program was introduced in Germany. Women between age 20 and 34 now continue to have annual cytology examinations, while women over the age of 34 receive a co-test comprising cytology in combination with a high-risk HPV (hrHPV) test every 3 years. All women aged 20-65 are invited for testing by their health-insurance providers every 5 years (11-18).
Coronavirus disease 2019 (COVID-19) was declared a global pandemic on 11 March 2020, affecting countries worldwide, including Germany (19, 20). The COVID-19 pandemic led to upheavals and interruptions in health-care systems around the world (21). There have been numerous reports of reductions in primary sampling for cytology and HPV testing, as well as of fewer women being referred for colposcopy – resulting in a decline in the numbers of treatments for precancerous or cancerous lesions (21). In addition to the decline in cytology and HPV testing, the rate of HPV vaccinations dropped in the first months of the pandemic (22). In March 2020, the German government imposed physical distancing measures and contact restrictions affecting almost all parts of daily life, but health-care facilities remained open with stricter hygienic conditions (23). However, there are justified concerns that other non–COVID-19 conditions may have been affected by declining care (24). There was a decline in outpatient presentations for vascular events (stroke, transient ischemic attacks, and myocardial infarction) during the COVID-19 pandemic in Germany (24). This also raises concerns about a possible decline in screening for CC and its precursor lesions in Germany. In a cross-sectional study performed in the United States, the monthly numbers of new cancer diagnoses decreased after the start of the pandemic, although monthly counts returned to near prepandemic levels by the end of 2020 (25).
To the best of our knowledge, no data are available on cervical cancer screening in relation to the COVID-19 pandemic in Germany. There are also few long-term data on the course of cervical cancer screening during the whole period of the pandemic. The aim of this study was therefore to describe alterations in the numbers of colposcopy examinations, cytology analyses, HPV tests, and histologic results during the pandemic.
Patients and Methods
A team of seven colposcopists performed 6,518 colposcopies of the cervix at the nationally certified dysplasia unit in Erlangen University Hospital, between January 2018 and December 2022. The most common reason for referral to the Dysplasia Unit was abnormal cervical cytology. All patients (n=5,579) who underwent cervical colposcopy were included, regardless of the reason for referral. Women with an inadequate colposcopy were excluded. The annual numbers of the 2 years before the pandemic (2018 and 2019) were compared with the first 3 years of the pandemic (2020, 2021, 2022).
Colposcopy. In our Department, colposcopies are conducted using a Zeiss KSK 150 FC colposcope (26). The overall evaluation follows the colposcopic terminology for the cervix established by the International Federation for Cervical Pathology and Colposcopy (IFCPC) in 2011 (27-29). A conventional cytology of the cervix, a Test for HPV [Hybrid Capture 2 test (2015-2018); Abbott RealTime high-risk HPV assay on an Abbott m2000sp (2019-2020) or Roche cobas® 4,800 HPV test, multiplex reverse transcription polymerase chain reaction (RT-PCR; since 2020)], and application of 5% acetic acid to the cervix is done routinely for every woman who is referred with suspicious cytology. To conduct a more detailed examination of the cervix and vagina, Lugol’s iodine is sometimes utilized to enhance the visibility of precancerous lesions in the vagina that were previously not detectable (5).
IFCPC terminology. The colposcopic results are categorized based on the IFCPC terminology as either “normal” or “abnormal”, further divided into “minor”, “major”, and “suspicious for invasion/cancer”. In addition, the findings of “nonspecific” and “miscellaneous” are distinguished (27). If a significant abnormality or a lesion that raises suspicion of invasion is detected, a colposcopy-guided biopsy must be performed on the most suspicious area of the lesion using biopsy forceps (Seidl Biopsy Forceps ER076R; Aesculap AG, Tuttlingen, Germany). In cases where patients have multiple lesions, more than one biopsy may be necessary. Decisions regarding surgical treatment are made based on the results of cytology, HPV testing, and histological results (5). The cytology results are reported following the Munich III nomenclature, with the Bethesda classification provided in brackets.
Patient database. All information, such as colposcopic findings, cytology and HPV test results, histological outcomes, number of biopsies, type of transformation zone, and epidemiological outcomes, were systematically documented in a database for future research purposes (5).
Procedure after colposcopy. Women who had normal or minor changes were scheduled for regular check-up examinations. If the biopsy results indicated high-grade squamous intraepithelial lesion (HSIL), a decision was made to proceed with surgery. The choice of conization procedure varied depending on factors, such as the size of the lesion, type of transformation zone (TZ), and the patient’s age. Women under the age of 25 diagnosed with HSIL were selected for observation, as there was a high likelihood of regression (30). These women were scheduled for more frequent follow-up examinations, including cytology and colposcopy. If HSIL persisted or invasion was confirmed, surgical excisional treatment was performed. In such cases, a loop electrosurgical excision procedure (LEEP) with laser coagulation of the periphery or laser conization was conducted (5, 9).
Regulations during COVID-19 pandemic. During the COVID-19 pandemic, there were strict regulations for staff and patients on hygienic standards. Staff and patients had to wear a facial mask. Patients had to be unaccompanied, and they were all checked at the entrance to the building. They were denied access if they had symptoms of COVID-19 or fever, and they had to present a negative Corona test. These restrictions remained in place until April 2023.
Results
Between January 2018 and December 2022, 6,518 colposcopies were performed in 5,579 women. The numbers of colposcopies (1,200; 1,106; 1,254) and women (1,021; 923; 1,062) was stable during the years 2018-2020 and increased during 2021 and 2022 (for colposcopies 1,518 and 1,440, and for women 1,338 and 1,235). The numbers of cytology analyses also increased after 2021 in comparison with before the pandemic. The numbers of II-p (atypical squamous cells of undetermined significance, ASC-US) findings more than doubled, from 120 (10.4%) in 2018 to 294 (21.2%) in 2022. The numbers of IIID1 (low-grade intraepithelial lesion, LSIL) findings also increased after 2020, but remained fairly stable in relation to the total numbers. IIID2 (HSIL) findings were stable in total but decreased in relation to the total numbers. The numbers of IVa-p (HSIL) findings decreased from 200 (17.3%) in 2018 to 115 (8.3%) in 2022 (Table I). The numbers of hrHPV findings also increased for the two years 2021 and 2022. The rates of positive and negative hrHPV findings were similar over the years (Table II). The numbers of biopsies taken were similar over the years and ranged from 450 to 554. The ratios of cervical intraepithelial neoplasia (CIN) III/HSIL were between 29.1% and 38.4%. The total numbers of carcinomas also remained stable for 2018-2021, between 11 and 15 each year. In 2022, seven carcinomas were histologically confirmed in the Erlangen dysplasia unit (Table III). The numbers of operations performed were also higher in 2021 and 2022 in comparison with the years 2018-2020 (Table IV). The relative rates of CIN III/HSIL remained stable throughout the years. The total numbers of carcinomas increased slightly from 15 (6.6) in 2018 to 22 (7.4%) in 2022 (Table IV).
Cytology findings before and during the COVID-19 pandemic.
Human papillomavirus (HPV) findings before and during the COVID-19 pandemic.
Histological findings in biopsy samples before and during the COVID-19 pandemic.
Histological findings in surgical samples before and during the COVID-19 pandemic.
Discussion
This study provides an overview of the numbers of colposcopies, cytology analyses, hrHPV tests, histology samples, and operations carried out in a certified dysplasia unit during the 2 years before the COVID-19 pandemic and in the first 3 years of the pandemic. Increases were observed in the numbers of women and colposcopies in the years 2021 and 2022 during the pandemic in comparison with the years before the pandemic. This also led to an increase in cytology analyses, hrHPV findings, histology examinations, and surgery.
The increase in numbers during the pandemic is in contrast to many other published findings. There have been many reports stating that the number of women seen for cervical cancer screening dropped significantly during the first month of the pandemic (19, 21, 22, 31). Except for the first 4 weeks of the pandemic, scheduling in our certified dysplasia unit remained unaffected by the pandemic. During the first 4 weeks, all appointments for lichen, condylomata, vulvodynia, etc. were canceled. Women with HSIL+ requiring urgent treatment filled the appointment slots. During the pandemic, strict hygienic standards were in place, as described above. In many other countries, cervical cancer screening was interrupted by the pandemic. In Italy, the number of patients receiving spontaneous screening declined by 14% and use of the CO2 laser technique fell by 30% in the period March 1, 2020 to February 28, 2021 in comparison with March 1, 2019 to February 29, 2020 (31). In a Canadian study in Ontario, the reduction in cervical cancer screening was 51% in the first 6 months of the pandemic, but started to recover by August 2020, almost reaching prepandemic levels based on historical data (19). An Australian model suggests that the COVID-19 pandemic led to a 1.1-3.6% increase in cervical cancer diagnoses in that country. The same model estimated that between 2020 and 2022, more CCs would be diagnosed at a later stage, resulting in additional cervical cancer mortality, morbidity, or both in the longer term due to delays in diagnosis caused by the COVID-19 pandemic (19, 32). In the United States, when cervical cancer screening in January through June 2020 was compared with average monthly screening numbers in 2017-2019, a decline of 94% was observed after the national emergency declaration; even after stay-at-home orders were lifted, screening remained 35% below historical averages (22).
No data for Germany have yet been published. We observed stable data during the first year of the pandemic and an increase in cervical cancer screening rates in 2021 and 2022. There are two probable reasons for the increase. Firstly, the dysplasia unit in Erlangen was reorganized in 2020, increasing the number of time slots available for women with suspicious screening results (26). Secondly and more importantly, a new system for cervical cancer screening was implemented in Germany in January 2020. Women between 20 and 65 are now invited for cervical cancer screening by their health-insurance provider every 3 years. In case of suspicious cytology, these women are referred to dysplasia units (12). Before 2020, opportunistic screening was in place (11). The newly organized screening system will most likely increase the number of women attending for cervical cancer screening. This may be one of the reasons why the number of women increased despite the pandemic. Data from Italy show that spontaneous screening was more strongly affected by the reduction in activities than organized screening; this may have been linked to the fact that organized screening activities are entirely managed by the public health-care system in Italy, which may have resumed its activities earlier than other health-care facilities in which spontaneous screening is performed (31).
The numbers of IVa-p (HSIL) findings decreased significantly in 2022, to 115 (8.3%) in comparison with 221 (19.7%) in 2019. On the other hand, II-p (ASC-US) findings increased from 146 (13.0%) in 2019 to 236 (17.0%) in 2022. The reason for the decrease in IVa-p is unclear. The numbers of CIN III/HSIL findings were stable on both the histology samples obtained during colposcopic examinations and surgery. This effect is most likely not due to the pandemic, but to the newly organized screening system. The numbers of women with externally diagnosed findings of I (negative for intraepithelial lesion or malignancy, NILM)/II-p (ASC-US) and positive hrHPV tests who were referred to our dysplasia unit increased at the start of the new screening system (11). In previously published data from the dysplasia unit, we reported that 22.4% of women with II-p (ASC-US) and positive hrHPV had CIN III/HSIL (11). Fewer carcinomas were diagnosed histologically during colposcopic examinations. On the one hand, this is because in 2022 there were significant numbers of women with externally diagnosed histologic findings of CC without another biopsy in the dysplasia unit, while on the other hand many CIN III/HSIL findings represented microinvasive (pT1a1) carcinoma after excision. These effects have nothing to do with the pandemic. The total numbers of operations also increased in 2021 and 2022. Operations for CIN III/HSIL or carcinoma were not postponed during the pandemic, due to their urgency.
In order to reduce numbers of visits to health-care facilities and associated COVID-19 transmissions, HPV self-sampling was promoted in various countries (19, 33). Another advantage of self-sampling is the opportunity to overcome barriers to screening that prevent women from attending (21). Barriers to the uptake of cervical screening before the pandemic included embarrassment, fear of the procedure being painful, fear of the possibility of cancer, the view that screening is less relevant for some women, stigmatizing judgments in the woman’s community, inconvenience, physical disability, trauma, female genital mutilation (FGM), familiarity with the sample taker, and lack of understanding of the procedure (21). Nine percent of women did not wish to attend screening because of the COVID-19 pandemic (21). It is important to triage women more likely to benefit from screening in order to reduce the viral transmission (33). Another measure for reducing viral transmission was the extension of screening intervals. In Scotland, for example, the intervention depends on the presence or absence of hrHPV. If no HPV is found, the recall interval is now 5 years, regardless of age, which for the 25-49 age group represents an extension of 2 years (34). Another important point for increasing participation in screening is the need for greater education and public awareness. Forty-three percent of women stated that they would be more likely to attend screening if more guidance was made available to them (21).
Strengths and limitations. The strength of this study is the comparatively large group of women included. In comparison to other reports, this study covered almost the whole duration of the pandemic. Limitations are that the beginning of the pandemic was almost parallel to the start of the newly organized screening program. This is probably the most important potential element of bias in the study.
Conclusion
The COVID-19 pandemic led to temporary interruptions in health-care services around the world, with a reduction in the numbers of patients attending for screening examinations. We were able to increase the numbers of women during the pandemic. Patients had to adhere to strict hygienic standards. The numbers of CIN III/HSIL findings were stable or even increased during the pandemic. We were able to continue cervical cancer screening assessment during the pandemic.
Acknowledgements
English editing was carried out by Michael Robertson.
Footnotes
Authors’ Contributions
Conceptualization, F.A.S., M.W.B. and A.K.D.; data curation, F.A.S., M.C.K., A.K.D., C.G., A.H., A.K., M.W.B., G.M., C.E.S., A.S.B., A.S. and P.G.; formal analysis, F.A.S., W.A. and A.K.D.; methodology, F.A.S.; project administration, F.A.S.; writing – original draft, F.A.S., M.W.B. and A.K.D. All Authors have read and agreed to the published version of the manuscript.
Conflicts of Interest
P.G. has received honoraria from Novartis, MSD, and AstraZeneca. None of the other Authors have any conflicts of interest.
- Received November 13, 2023.
- Revision received December 28, 2023.
- Accepted January 15, 2024.
- Copyright © 2024 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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