2. Introduction – Cervical Carcinoma

The incidence of cervical carcinoma has declined markedly during the last 30 years. This is mainly due to the early cancer detection program introduced in 1971. However, the reduction in the incidence, partly due to treatment of preinvasive lesions, has not led to a marked reduction in the mortality rate and, in particular, the morbidity rate among patients with cervical carcinoma during the last ten 10 years (see also Chapter 3). It has not yet been possible to change this situation, despite continuing technical progress and the introduction of innovative new treatment approaches. However, current surveys on quality assurance measures show that treatment for patients with cervical carcinoma continues to be extremely heterogeneous. Many different treatment variants, with combinations of different approaches, are being used for patients. When these combined approaches and the literature reports are put together, it can be seen that there are at present more than 20 different treatment options available in the adjuvant setting for a patient with cervical carcinoma. This shows that the treatment standards used, and consequently the quality of the treatment provided, are highly variable. This might indirectly be one reason for the lack of significant improvements in relation to patients’ survival and treatment-related morbidity in recent years.

The problems of uncertain treatment, mortality and morbidity rates that have not declined during the last 15 years, and the current wide variations in treatment make an upgrading from the existing Level 2 consensus-based guideline to a Level 3 guideline necessary.

The aims of the Level 2 consensus-based guideline “Diagnostics and Treatment of Cervical Carcinoma” [1] were maintained, supplemented, and made more specific in 2014. Sections on prevention and early detection were placed in a separate Level 3 guideline on “Prevention of Cervical Carcinoma” (AWMF register no. 015/027OL). In general, the aim is to provide physicians working in private practice and in hospitals in the field of oncology with an accepted,— and as far as possible evidence-based — decision-making aid for selecting and carrying out appropriate measures in the diagnosis, treatment, and follow-up of patients with cervical carcinoma.

The recommendations are based either on an examination of the available evidence in accordance with the criteria of evidence-based medicine, adaptation of existing evidence-based national and international guidelines, or — in the absence of an evidential basis — on a consensus of participating specialists. All of the recommendations have been evaluated and voted on by a multidisciplinary group of specialists and representatives of patients’ organizations.

In addition to the general goal of improving care for patients with cervical carcinoma by optimizing the diagnostic chain and carrying out stage-appropriate treatment when the patient first contracts the disease, and at recurrence and/or metastasis, the aims of this revised Level 3 guideline are as follows:

• Establishment of a “quality standard” as the basis for individually tailored, high-quality treatment;
• Improvement of the patients’ quality of life and achieving a medium-term to long-term reduction in the mortality rate among these patients by implementing the guideline’s recommendations;
• Ensuring universal implementation of multidisciplinary, quality-assured and inter-sector care for patients with cervical carcinoma, while at the same time making specific efforts to improve psychosocial care and rehabilitation in a need-oriented and quality-assured way;
• Providing support for physicians and patients in medical decision-making by providing recommendations that have received formal consensus;
• Supporting the involvement of the patients in treatment decision-making, taking their individual needs into account;
• Creating the basis for education, training, and further training measures with targeted contents for physicians, with the guideline recommendations being systematically taken into account in education, training, and further training and in quality management systems;
• Obtaining information about the status quo in medical care, with particular reference to quality indicator 6 on adjuvant radio(chemo)therapy, — as there are no data currently available on the way in which many patients receive stage-appropriate adjuvant therapy with combined cisplatin-containing radio(chemo)therapy. In the long term, the aim is to achieve a reduction in the numbers of adjuvant treatments in favour of primary chemoradiotherapy in the group of patients at risk, or unimodal therapy.

The goals set out in the guideline remain the same as in the first version. The guideline on “Diagnosis, Treatment, and Follow-Up in Patients with Cervical Carcinoma” is intended as an evidence-based and consensus-based instrument for the care of patients with cervical carcinoma. It serves to offer patients scientifically based, up-to-date, and economic procedures in diagnosis, treatment, follow-up, and rehabilitation that are appropriate to the relevant state of the disease. The present version of the guideline is intended to provide the basis for medical decision-making processes that are relevant to practical action. This is also against the background of the “shared -decision-making” approach. Shared “decision-making” is a model for a partnership-based doctor patient relationship, characterized by a common and equal decision-making process. The information provided in the guideline can enable physicians to help patients achieve their wish to participate in decisions about their health problem. On the basis of the information provided in the guideline, physicians and patients can communicate on a basis of partnership about the objective and subjective aspects of an upcoming decision.

The guideline is intended to contribute to ensuring appropriate health care in the diagnosis, treatment and follow-up of patients with cervical carcinoma and to provide the basis for individually stage-adapted, quality-assured therapy that respects the patient’s wishes. Like its predecessor, this revised Level 3 guideline allows national implementation of interdisciplinary, quality-assured, inter-sector therapy. The aim of comprehensive distribution and implementation of the revised Level 3 guideline is to improve the diagnostic chain and stage-appropriate therapy both for the initial disease and also for recurrences and metastases.

Group of patients

This Level 3 guideline is aimed at all patients who have developed cervical carcinoma (cancer of the uterine cervix) (including microinvasive lesions / high-grade precursor lesions but excluding early stages / preinvasive lesions), as well as their relatives.

Target group of users

The recommendations given in the guideline are aimed at all physicians and members of professional groups who are concerned with outpatient and/or in-patient care for patients with cervical carcinoma — particularly gynecologists, gynecological oncologists, radiologists, pathologists, radio-oncologists, psycho-oncologists, and nursing staff.

The guideline also continues to provide information for family physicians and hemato-oncologists.

The intended audience also includes:

• Medical and scientific specialist societies and professional associations
• Groups representing the interests of women (women's organizations, patients' organizations, and self-help organizations)
• Quality assurance institutions and projects at the national and state level (e.g., AQUA, KoQK, ADT, IQWiG, GEKID, „gesundheitsziele.de”, IQTIG)
• Health-policy institutions and decision-makers at the national and state level
• Certification institutes (e.g., DKG)
• Funding bodies

The guideline is valid until the next updating, or at the latest  until October 2025. Its need for updating is continuously monitored. The current literature is researched and methodically reviewed on an annual basis in a “living guideline” framework. The central guideline group decides on the need to update individual chapters.

When necessary — e.g. when studies providing relevant results or warnings become known — the updating procedure can be started earlier or a short-term amendment to the guideline may be made, depending on urgency.

Comments and suggested changes would be welcomed at the following address:

Prof. Dr. M. W. Beckmann
Dr. Frederik A. Stübs
Central Guideline Coordination (Level 3 Guideline on Cervical Carcinoma)
Universitätsfrauenklinik Erlangen
Universitätsstrasse 21 - 23
91054 Erlangen
Germany

fk-leitliniensekretariat@uk-erlangen.de
Tel:      +49-9131 85-33553
Fax:     +49-9131 85-33445

The system developed by the Scottish Intercollegiate Guidelines Network (SIGN), presented in Table 3, has been used in this guideline to classify the risk of distortion in the studies identified (see http://www.sign.ac.uk/pdf/sign50.pdf).

Table 3: The SIGN evidence classification scheme

Grade	Description
1++	Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of systematic error (bias)
1+	Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of systematic error (bias)
1-	Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of systematic error (bias)
2++	High-quality systematic reviews of case control or cohort studies or High-quality case control or cohort studies with a very low risk of systematic distortion (confounding, bias, chance) and with a high probability of the association being causative
2+	Well-conducted case-control studies or cohort studies with a low risk of systematic distortion (confounding, bias, chance) and a moderate probability of the association being causative
2-	Case-control studies or cohort studies with a high risk of systematic distortion (confounding, bias, chance) and a significant risk of the association not being causative
3	Nonanalytic studies, e.g., case reports, case series
4	Expert opinion

 

Statements/recommendations that have been decided on the basis of an expert consensus in the guideline group are marked as „expert consensus (EC)”. No symbols have been used to grade these recommendations; the strength of the expert consensus is indicated by the form of expression used (shall, should, or can) in accordance with the gradation given in Table 4.

Expert consensus (EC) after systematic research
Systematic research was carried out on a few key questions, without any relevant literature related to them being identified. The following study designs were defined as inclusion criteria for all population, intervention, comparison, and outcome (PICO) questions:

• Randomized controlled studies (RCTs), including quasi-randomized controlled studies.

• Nonrandomized controlled studies (non-RCTs) — i.e., experimental prospective studies that only differ from RCTs in that the assignment of patients to the intervention groups was carried out without randomization, while the intervention groups were compared with each other.

• Prospective comparative observational studies.

• Systematic reviews on the above-mentioned study designs, with the following characteristics: 
  
  • The literature search was carried out in at least two electronic databases.
  • The study question was formulated as a PICO question.    
  • The description of the study population, the results of the analysis of the risk of bias, and the   results were presented in tabular form and comparably, in such a way that they can be clearly assigned to the individual studies.

As these questions were prioritized in advance for external processing, due to their high level of clinical relevance, the guideline group nevertheless formulated statements/recommendations on them. In the absence of data, these were thus ultimately based on an expert consensus in the guideline group. These statements/recommendations are marked as “expert consensus (EC) after systematic research” and linked to the corresponding key questions. The precise research strategy and research results are explained in the guideline report. Symbols are not used to grade these recommendations; the strength of the expert consensus is conveyed by the formulation used (must/should/can) in accordance with the gradation given in Table 4. The way in which the grade of recommendation was established, in view of the absence of an evidence base, is explained in each background text.

German Cancer Aid (DKH) provided the funding for the preparation of the guideline, via the Oncology Guideline Program. These funds were used for staff costs, office materials, purchasing of literature, and for the consensus conferences (room hire, technical facilities, catering, chairpersons’ fees, participants’ travel costs). The guideline was prepared with editorial independence from the funding organisation. All members provided a written declaration concerning any conflicts of interest during the guideline preparation process. The disclosed conflicts of interest are listed in the guideline report for this guideline (https://www.leitlinienprogramm-onkologie.de/leitlinien/zervixkarzinom/).

In accordance with the requirements of the AWMF, all members of the guideline group were asked to disclose their conflicts of interest at the beginning of the guideline project. For this purpose, a standardized AWMF form was sent to all members. Submission of a completed conflict of interest (COI) form was mandatory for further participation in the guideline process. This applied not only to office-holders, but to everyone involved in the guideline. If the form was not available prior to the commencement of substantive work, it automatically resulted in disqualification from participation. The evaluation procedure for COIs was explained in detail to the guideline group at the first consensus conference. All COI forms were reviewed by the guideline coordinators and classified in accordance with formal criteria into the categories shown in Table 6. The guideline coordinators were not permitted to have any guideline-specific financial COIs (even of minor relevance). The results of this evaluation were presented at the first guideline group consensus conference.

Table 6: Categories for evaluating conflicts of interest

Category	Classification
Low	Less than moderate
Moderate	Advisory work / industrial third-party funding or speaking fees > with an absolute value > 5000€/year, share ownership ≤ 5000€
High	Share ownership < 5000€; patent ownership, third-party funding > € 50,000€

 

Guideline staff in supervisory positions (e.g., as members of steering committees / steering groups, working group leaders, persons primarily responsible for evidence preparation, chairpersons) were permitted to have a maximum of low COIs. Office-holders with a moderate or high COI were not permitted to vote on the topic-related statements/recommendations and had to abstain from voting. Unless their expertise could be dispensed with, they had the status of advisory, nonvoting experts.

The guideline group was composed of representatives from various specialist disciplines as well as members of the Oncology Guidelines Office, the AWMF, the DKG, and patient representatives. The study evidence was reviewed by external collaborators.

Before the second consensus conference and before voting on the statements and recommendations, all office-holders and participants in the guideline group were asked to update their COI statements. These were then presented again at the second consensus conference.

All statements and recommendations were approved with a strong or very strong consensus.

All COIs are published along with names in the guideline report (without stating the financial sums concerned).

Topicality of recommendations and statements

It has been noted in the headers of the recommendations and statements when they were created or updated and whether they have been modified or newly created. The following categories of marking are used:

• Checked 2021: the recommendation or statement was made at the time when the guideline was written (2014). The validity of the recommendation or statement was reviewed during the 2021 update process, and a decision was made to retain the content.
• Modified 2021: the recommendation or statement was modified in part or in its entirety during the 2021 update process.
• New 2021: the recommendation or statement was made for the first time during the 2021 update process.