The Epidemiology of Cervical Cancer in Germany

A register-based analysis of incidence, survival, and tumor characteristics (2003–2021)

Background: Cervical cancer is the fourth most common type of cancer in women worldwide. Its incidence and mortality have been declining in Germany since 1971, when cervical cancer screening began to be offered to all women in the German statutory health care system. In this study, we examine the trends in incidence and survival since 2003.

Methods: We analyzed data from the epidemiological cancer registries of 10 German federal states concerning the incidence of cervical cancer (ICD-10 C53) from 2003 to 2021. The data, obtained via the Center for Cancer Registry Data at the Robert Koch Institute, were classified according to tumor stage, histological subtype, histopathological grade, and patient age. Survival rates were calculated with Cox regression models.

Results: During the study period, the mean age at diagnosis was 53.5 years. The 5-year overall survival rate did not change (2003 and 2017: 65.4% in both years). The age-standardized incidence of squamous cell carcinoma declined from 11.5 per 100 000 women in 2003 to 7.7 per 100 000 in 2021. 25.4% of women with the disease were ≥ 65 years old; compared to younger women, they more often had stage T3 and T4 disease and grade G3 tumors, and their 5-year survival rate was lower. 10.8% of the women with cervical cancer were under 35 years old. The incidence fell most sharply in this age group, from 5.1 per 100 000 women per year in 2003 to 3.1 per 100 000 per year in 2021, and women in this age group were also the most likely to have stage T1a or T1b disease.

Conclusion: The incidence of squamous cell carcinoma of the cervix declined most markedly in the youngest age group, and this may be attributable to vaccination against HPV. The 5-year survival rates have not changed. The impact on survival of the organized screening program and treatment in certified gynecological cancer centers remains to be seen.

Cite this as: Stuebs FA, Beckmann MW, Poeschke P, Heindl F, Emons J, Gaß P, Haeberle L: The epidemiology of cervical cancer in Germany: A register-based analysis of incidence, survival, and tumor characteristics (2003–2021). Dtsch Arztebl Int 2025; 122: 483–8. DOI: 10.3238/arztebl.m2025.0105

Cervical cancer is the fourth most common carcinoma in women worldwide (0.57 million cases), ranking twelfth among women in Germany (1, 2, 3). In 2022, there were 4388 new cases of cervical cancer in Germany (4). Squamous cell carcinoma is the most common histological subtype, accounting for approximately 80% of all cervical cancer cases, followed by adenocarcinoma, accounting for 10–20%. Neuroendocrine carcinoma of the cervix (NECC) is much rarer (5). Since cervical cancer screening began to be offered to all women in the German statutory health care system in 1971, its incidence has been declining, most notably until the early 2000s (5, 6). This figure has fallen slightly again over the last ten years (3). The mean age at diagnosis is 53 years, both globally and in Germany (1, 3). As the result of the statutory German cancer screening program, cervical cancer mortality has declined. Twenty years ago, more than 2020 women died of cervical cancer in Germany every year (age-standardized mortality rate of 3.5/100 000 women). In 2022, 1528 women died of this diagnosis (age-standardized mortality rate of 2.2/100 000 women) (4). The relative 5-year survival in patients diagnosed with invasive cervical cancer is 64% (3). In international comparison, countries with long-established statutory cancer screening programs have lower mortality rates (3).

Persistent infection with the sexually transmitted human papillomavirus (HPV) is the main risk factor (7). A necessary pre-requisite for the development of cervical cancer is a persistent HPV infection (8). Besides persistent infection with HPV, smoking is one of the key risk factors (5). Further risk factors include immunosuppression (HIV, immunosuppressants), early start of sexual activity, promiscuity, and low socioeconomic status (5).

A new organized statutory cervical cancer screening program was introduced in Germany in 2020. The contents of the cervical cancer screening program are regulated by the German Federal Joint Committee (G-BA, gemeinsamer Bundesausschuss) in the guideline for Organized Cancer Screening Programs (oKFE-RL, Richtlinie über die Durchführung der organisierten Krebsfrüherkennungsprogramme) (9). Women aged 20 and older are entitled to participate in the program (9). Women aged between 20 and 34 continue to receive an annual cytology examination. Women who are 35 years of age and above are offered a co-test, comprising a HPV test and a cytology examination (including a clinical examination) (9, 10). Irrespective of the organized screening program, women can continue to have one gynecological examination annually, if they have not already received one as part of the organized program (9).

In this study, we analyze the incidence and overall survival of women with cervical cancer during the period from 2003 to 2021 based on cancer registry data with complete capture, taking into account tumor stage, histological subtype, histopathological grade, and patient age.

Methods

Data

The Center for Cancer Registry Data (ZfKD, Zentrum für Krebsregisterdaten) of the Robert Koch Institute (RKI) provided the cervical cancer incidence data upon request (4).Only data from women aged 18 and over from cancer registries with a sufficiently complete capture (estimated degree of capture >90%) were included in our analyses.

Data from the following cancer registries for first diagnoses between 2003 and 2021 were evaluated: Schleswig-Holstein, Hamburg, Lower Saxony, Bremen, Saarland, Brandenburg, and Saxony. Data for North Rhine-Westphalia and Rhineland-Palatinate from 2008 onwards and for Baden-Württemberg from 2013 onwards were also taken into account. We included exclusively patients who were not cases documented by death certificates only (DCO), (11, 12) (for details, see eMethods).

For the analyses, cervical cancer (ICD-10 C53) was histologically classified as squamous cell carcinoma, adenocarcinoma or neuroendocrine tumor (NET) (eTable 1). Tumors were classified by tumor size (T stage), histopathological grade and nodal status. T stages have not changed in the various editions of the TNM classification (5). Patients were assigned to age groups based on the age classification in the organized cancer screening program: 18–34 years, 35–64 years and ≥ 65 years (the latter are not invited to participate in the screening program) (9).

eTable 1

Assignment of ICD-O-3 morphology codes to histological groups and frequencies of morphology codes

Statistics

The patient and tumor characteristics were summarized descriptively. We calculated the mean and standard deviation (SD) as well as the median and the first and third interquartile range (IQR) for continuous variables. In addition, descriptive statistics were compiled by age group. Patients with unknown tumor characteristics formed separate groups in the analyses.

In order to analyze changes in the composition of the patient sample over the diagnosis period, the descriptive statistics mentioned above were calculated separately for each diagnosis year and presented in a graphic format. The data of the margin years (2003, 2021) were also shown in table format.

To calculate the (absolute) overall survival rates over the diagnosis period (2003–2017), Cox regression models were applied, using the period from diagnose to death as the outcome variable and the diagnosis year as a continuous predictor (for details, see eMethods).

Crude and age-standardized incidence rates were calculated based on the Revised European Standard Population 2013 for each diagnosis year (13).

Results

Altogether, 38 296 case were included. Of these, 4142 (10.8%) were aged 18 to 34 and thus of reproductive age. At the time of diagnosis, about a quarter of affected women were older than 65 years (for the distribution of patient and tumor characteristics, see Table 1, Table 2, eTable 2, eTable 3, eFigure 1a–e). The mean age at the time of diagnosis was 53.5 years (standard deviation: 15.7 years); the median age was 52 years (eTable 2). The mean and median age at diagnosis did not change over the study period (eFigure 1a). Of all tumors, 82.7% were squamous cell carcinomas, followed by 16.8% adenocarcinomas (eTable 2). Table 1 shows that the percentage distribution of the histological subtypes remained largely unchanged across the different age groups. The age-standardized incidence rate per 100 000 women in the total population declined continuously (2003: 13.2 and 2021: 9.7) (Figure 1a, Table 2). The incidence rate (crude and age-standardized) of squamous cell carcinoma was lower in 2021 compared to 2003. Over the same period, the incidence of adenocarcinoma did not change (Figure 1b, Table 2; for details, see eResults in the eMethods section, eFigure 2a, eFigures 2 b and c).

Figure 1a

Crude (solid lines) and age-standardized (dashed lines) incidence rates: Number of new cases per year per 100 000 women for all patients

Figure 1b

Histology—crude (solid lines) and age-standardized (dashed lines) incidence rates for all patients

Table 1

Tumor characteristics by age group

Table 2

Relative frequencies as well as crude and age-standardized incidence rates (number of new cases per year per 100 000 women for the years 2003 and 2021) based on the European Standard Population 2013

eFigure 1a

Distribution of patient and tumor characteristics by year of first diagnosis: Mean and median age at first diagnosis

eFigure 1b

Distribution of patient and tumor characteristics by year of first diagnosis: Percentage distribution of histology

eFigure 1c

Distribution of patient and tumor characteristics by year of first diagnosis: Percentage distribution of grades

eFigure 1d

Distribution of patient and tumor characteristics by year of first diagnosis: Percentage distribution of tumor stage

eFigure 1e

Distribution of patient and tumor characteristics by year of first diagnosis: Percentage distribution of nodal status

eFigure 2a

Crude (solid lines) and age-standardized (dashed lines) incidence rates: Number of new cases per year per 100 000 women by age group

eFigure 2c

Nodal status—crude (solid lines) and age-standardized (dashed lines) incidence rates

eTable 2

Patient and tumor characteristics (including place of residence)

eTable 3

Patient and tumor characteristics by federal state

Grade 2 tumors were the most common type in all age groups. The proportion of grade 1 tumors was significantly higher among women aged under 35 than in the other age groups and decreased with increasing age (Table 1). The proportion of grade 3 tumors increases with increasing age at first diagnosis. No relevant percentage change in tumor grades was observed in the total sample over the observation period (eFigure 2b).

eFigure 2b

Grade—crude (solid lines) and age-standardized (dashed lines) incidence rates

T1 tumors were the most common, accounting for about half of all cases, followed by T2 tumors (eTable 2). Among patients under the age of 35, 74.4% of tumors were in stage T1 (Table 1). The incidence of the various tumor stages remained largely unchanged throughout the observation period (Figure 1c). A continuously declining incidence rate was only demonstrated for stage T1b.

Figure 1c

Tumor stage—crude (solid lines) and age-standardized (dashed lines) incidence rates

Both the unadjusted 5-year survival and the 5-year survival adjusted for age at diagnosis remained unchanged over the observation period (2003 and 2017: unadjusted 65.4%, respectively; eTable 4, Figure 2a). With increasing age of women with cervical cancer, the 5-year survival deteriorated (2017: <35 years: 89.6%; 35–64: 69.7%, and ≥ 65 years: 38.5%; see eTable 4, eFigure 3a). With higher tumor grades and stages, the probability of survival declines (unadjusted 5-year survival 2017: G1: 89.7%; G3 58.4%; T1a: 95.2% T4: 20.3%; eTable 4, eFigure 3b, c). The probability of survival also decreases if nodal metastasis is found (eTable 4, Figure 2b). The 5-year survival rates for patients with squamous cell carcinoma or adenocarcinoma declined slightly over the observation period (eTable 4, eFigure 3d).

Figure 2a

5-year survival rates by year of first diagnosis for all patients: unadjusted (solid lines) and age-adjusted (dashed lines) survival rates

Figure 2b

5-year survival rates by year of first diagnosis, stratified by nodal status: unadjusted (solid lines) and age-adjusted (dashed lines) survival rates

eFigure 3a

5-year survival rates by year of first diagnosis by age group

eFigure 3b

5-year survival rates by year of first diagnosis stratified by grade: Unadjusted (solid lines) and age-adjusted (dashed lines) survival rates

eFigure 3c

5-year survival rates by year of first diagnosis stratified by tumor stage: Unadjusted (solid lines) and age-adjusted (dashed lines) rates

eFigure 3d

5-year survival rates by year of first diagnosis for all patients with squamous cell carcinoma or adenocarcinoma: Unadjusted (solid lines) and age-adjusted (dashed lines) survival rates

eTable 4

5-year survival rates (in %) with 95% confidence intervals for the years of first diagnosis 2003 and 2017

Discussion

In this study on the epidemiology of cervical cancer in Germany, which is based on cancer registries of 10 German federal states, the mean age at diagnosis remained stable. The incidence of cervical cancer declined during the study period. The 5-year survival rates did not changed between 2003 and 2017. The majority of women with cervical cancer were between 35 and 64 years of age. In women under the age of 35, low tumor stages and G1 tumors were significantly more common than in other patient groups. During the period analyzed, the incidence of squamous cell carcinoma declined, while the incidence of adenocarcinoma remained unchanged.

In the WHO classification 2020, a distinction is made between HPV-associated and HPV-independent cervical cancer. Squamous cell carcinoma is mainly caused by persistent HPV infection (14). HPV-independent adenocarcinoma has a significantly poorer prognosis compared to HPV+ adenocarcinoma (15, 16). In addition, the rate of lymphatic vessel invasion and nodal metastasis is significantly higher in patients with HPV-independent adenocarcinoma (17). The stable incidence of adenocarcinoma may be attributable to the endocervical growth pattern of the pre-invasive lesions and the resulting delay in detection as well as the partly HPV-independent etiology (2, 18, 19).

On a global scale, the incidence rates of cervical cancer show considerable regional variation. The worldwide age-adjusted incidence is estimated to be 13.1 per 100 000 women in 2018 (2). The low incidence of cervical cancer in Germany (age-adjusted incidence in 2018: 9.3) is largely attributable to the cytological smear-based statutory cancer screening program, which was implemented in 1971 (3, 4, 20). It has enabled timely detection and successful treatment of precancerous lesions and early stages of cervical cancer (5, 21). Approximately 56% of all cervical cancers diagnosed in Germany in 2016 were detected via the screening program (4, 22). Since the introduction of cervical cancer screening, a reduction in incidence has also been observed in other countries, such as the USA (23).

During the period 2017–2019, the rate of participation in the opportunistic cervical cancer screening program was 37% (24). According to 2021 and 2022 screening program data, participation rates were at 45.2% and 47.1% for the statutory organized cancer screening program and the cytology-based primary screening of women under the age of 35, respectively. For the co-test offered to women aged 35 and above, the estimated participation rate was 9.2% (2021) and 5.1% (2022) across all age groups. The participation rate fell from 20.8% in the age group 35–39 years to less than 10% in the age group 55 years and above. The authors, however, point out that the number of participants in the co-test is potentially underestimated. They did not take the year 2020 into account due to a lack of mandatory documentation, the evaluation center did not yet have all data available and a connection to the cancer registries of German federal states is still missing (25, 26). The high rates of T1a and T1b tumors observed in women below age 35 may be attributable to the high participation rates among young women. Early detection of cervical cancer and its precursors is particularly important in women of childbearing age, as it is a prerequisite for organ-preserving surgical treatment (6, 27). The rate of participation of older women aged 65 and above in the statutory screening program is significantly lower (below 5%). In this study, we found a significantly increased frequency of advanced T3 and T4 tumors (9.9% and 8.8%, respectively) for this age group, and 23.1% of the affected women had T2 tumors. This is likely to be one of the reasons for the comparatively low 5-year survival. Since many older women only see a gynecologist if they experience symptoms, higher tumor stages are found at the time of first diagnosis which in turn are associated with a poorer prognosis and increased mortality. Commonly, older patients are treated less aggressively and not in compliance with the guidelines, a fact that has an additional negative impact on prognosis (28, 29). Whether the statutory organized cancer screening program will further reduce the incidence and mortality of cervical cancer remains to be seen.

Primary prevention via HPV vaccination is one way to reduce the incidence of cervical cancer. The German Standing Committee on Vaccination (STIKO, Ständige Impfkommission) has recommended HPV vaccination for girls since 2007. This STIKO recommendation has been expanded to cover boys and girls aged 9 to 14 years since 2018 (30). The effect of HPV vaccination was demonstrated in a Swedish registry study. After adjustment of all covariables, the incidence rate was 0.12 (95% confidence interval: [0.00; 0.34]) for women who had been vaccinated with the quadrivalent HPV vaccine prior to age 17 (31). Another study showed that the earlier a child is vaccinated, the better the protection by the vaccination (32). For the first time, data on the potential effects of HPV vaccination are now available from Germany. In women born in 1992, the incidence of having cervical cancer was 24% lower compared to women of the reference cohort born in 1989 (relative risk: 0.76; [0.68; 0.86]) (33). Nationwide, 55% of 15-year-old girls had received a complete HPV vaccination series (34). Given that vaccinations are mainly administered to adolescents, the incidence and mortality rates in the older unvaccinated population will remain unchanged. In this study, we found that the relative decrease in age-standardized incidence rates was highest in the group of the 18– to 34-year-olds. To achieve a significant reduction in cervical cancer incidence, it is necessary to increase the vaccination coverage rates among children and adolescents.

The first gynecological cancer centers certified by the German Cancer Society (DKG, Deutsche Krebsgesellschaft) and the German Society of Gynecology and Obstetrics (DGGG, Deutsche Gesellschaft für Gynäkologie und Geburtshilfe) were established in 2008 (35). The certification system for gynecological dysplasia clinic and gynecological dysplasia units was introduced in 2014 to facilitate access to certified gynecological cancer centers and establish a longitudinal care chain (36, 37). The WiZen study showed a higher overall survival in women who received initial cancer treatment in a certified gynecological cancer center. In women with cervical cancer, this lead to an absolute risk reduction of 4.61 months (hazard ratio [HR] 0.83 [0.76; 0.92]; P = 0.001). During the study period 2009–2017, however, the majority of patients with cervical cancer underwent initial treatment in a non-certified hospital (38). The proportion of women treated in certified gynecological cancer centers needs to increase to ensure that overall survival rates do improve.

With the introduction of new therapies, studies found improved survival rates in women with cervical cancer. One example is bevacizumab which was granted approval for the treatment of women with metastatic cervical cancer during the observation period of this study. For this drug, a significant survival benefit was shown (16.8 versus 13.3 months (HR 0.77 [0.62; 0.95]; p = 0.007) (39). It thus remains to be seen what effect new treatments (e.g., pembrolizumab, cemiplimab and tisotumab vedotin) will have on overall survival in the total population of patients with cervical cancer.

Strengths and weaknesses

In this study, we examined a large cohort of 38 296 cases of cervical cancer. For the majority of German federal states, the study period of almost 20 years is comparatively long. Three further federal states were included later during the study period when they had achieved completeness of their data. This change of the population has the potential to create bias in the data. However, it was possible to significantly increase the total number of included cervical cancer cases. We conducted a sensitivity analysis to rule out potential bias (eSupplement). In addition, tumor-related information, such as tumor stage, grade and nodal status, is missing in some cases. This can also be a source of bias in the data

Conclusion

The incidence of squamous cell carcinoma has declined since 2003. The mean age at diagnosis and the 5-year survival rates remained stable. The statutory organized cervical cancer screening program is a strategy to reduce mortality by detecting well-treatable severe cervical dysplasia and early tumor stages. To achieve a reduction in the overall incidence of cervical cancer, participation rates must significantly increase, in particular in the population of women older than 65 years. In addition, cervical cancer patients should be treated in certified centers in order to improve their prognosis. The HPV vaccination rate needs to increase further. Future analyses will show whether and to what extent these measures will improve survival in the total population of patients with cervical cancer.

Acknowledgement

We would like to thank the Robert Koch Institute and the Center for Cancer Registry Data, specifically Nina Buttmann-Schweiger, Karsten Berg and Klaus Kraywinkel, for their methodological support in the preparation of this paper.

Conflict of interest
The authors declare no conflict of interest.

Manuscript received on 21 November 2024; revised version accepted on 5 June 2025

Translated from the original German by Ralf Thoene, M.D.

Correspondence
PD Dr. med. Frederik Stuebs

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