Cervical Cancer

An overview of disease, diagnosis and treatment

Cervical Cancer

The cervix and cervical canal are the most distal parts of the uterus. 

Pre-malignant cervical lesions can be detected on screening smear  examinations. A smear tests is a screening tool, and in case of suspicious cervical lesions/tumor, the patient must be referred for specialized conclusive examination to determine, if a lesion is malignant or not.

Patients with severe dysplasia or carcinoma in situ (pre-malignant cervical lesion) may be recommended to undergo conisatio of the cervix, to prevent progression to actual cervical cancer.

Within the last decades extensive screening programs were introduced, especially in developed countries. The number of deaths from cervical cancer has effectively declined with the introduction of the screening programs and also HPV-vaccination.

Cervical cancer differs from uterine (endometrial) cancer regarding symptoms/presentation, histology, treatment and diagnosis.

Epidemiology

The majority of cervical cancers are related to persistent Human Papilloma Virus (HPV) infection, especially with the high-risk oncogenic HPV types 16 & 18. 

Patients diagnosed with cervical cancer include both very young patients in their 20’s, as well as older women.

The prognosis is dependent on the tumor stage and cell-type(s) of the cancer. It significantly affects the outcome for the patient, if the tumor has spread to local pelvic lymph nodes, para-aortic lymph nodes, bladder, rectum, or distant organs.

Diagnosis

A suspicion of cervical cancer can be based on results from smear screening, or clinically based on symptoms, or objective findings during a gynaecological examination.

Often early stages of cervical cancer do not give symptoms. Later on patients may experience bleeding, contact-bleeding during intercourse, changes in vaginal discharge, pain, bladder/bowel symptoms or leg-swellling.

Upon a suspicion of cervical malignancy patients must be referred for specialist gynaecological examination, incl. colposcopy (microscopic examination of the cervical surface lining), biopsies, and scraping from the cervical canal. All tissue samples (biopsies) taken out are send for histological verification.

The prognosis of cervical cancer depends on the histological type, stage and possible spread of the cancer at initial diagnosis. 

In many specialized facilities treating patients with cervical cancer, the woman (with cervical cancer over stage 1A) is clinically staged under full anesthesia. If involvement of bladder or rectum is suspected, a cystoscopy and/or rectoscopy must also be performed.

The extent of disease and possible spread to lymph nodes/distant organs are evaluated by radiological examination with either PET/CT, CT or MRI scan, before deciding upon the treatment plan.

Examinations methods

Cervical Colposcopy

Cervical colposcopy is performed by specialist gynaecologists. The colposcope (microscopic tool) is inserted through the vagina during an ordinary gynaecological examination. Through the microscope the doctor can inspect for abnormal lining, tumors, and bleeding of the portio (cervical mouth). 

In case of suspicious area(s), or abnormal tissue/cells, the doctor performs biopsies/cervical scraping, and the retrieved tissue samples are send for histological examination. 

HPV Test

Infection with Human Papilloma Virus (HPV) can be detected by examining for genetic material from HPV. The majority of cases of HPV infection is cleared by patients spontaneously. However, in a minority with persistent HPV infection, it may lead to pre-cancerous or even cancerous lesion in the cervix. Therefor regular screening smear test is recommended, for possible lesions to be detected early.

Smear Test (Pap test/ Pap smear)

During a gynaecological examination with smear test, cells are retrieved from the cervical surface lining. The material is send for pathological examination, where the histologically stained cells are inspected through a microsope.

More specifically, cervical cells are removed by scraping and brushing the cervix, then spread on a slide, stained with a special staining solution (which identifies atypical/malignant cells), and then microscopically quantified.

A smear test is used as a screening tool for the early detection of abnormal or cancerous cells, and its preliminary stages. If actual cancer is suspected, then a smear test is insufficient, and the patient must have representative biopsies taken and examined for histological verification.

Treatments

Cervical cancer can be treated with either surgery, radiation, chemoradiation, or chemotherapy depending on the stage and possible spread of the disease. The recommended treatment option is best decided after thorough staging and evaluation of histological tumor tissue (biopsies).

In early stages (1A-1B) complete surgical removal can be recommended. If unsuspected spread to lymphnodes is followingly verified, patients may be referred for postoperative radiation/chemoradiation as well.

Patients presenting with physical symptoms often have advanced tumours (stage 2-3), and therefor are more difficult to treat. These patients will instead of surgery be referred directly to an oncological department for radiation/chemoradiation. Patients with advanced stage 4B disease can receive treatment with chemotherapy.

Cervical cancer is optimally treated in specialized centers where oncologists/gynaecologist work in a multidisciplinary team with radiologists, pathologists, radiation therapists, and specialized nursing staff.

Surgery

The earliest stage of cervical cancer can be treated with limited surgery (conization), where a cone-shaped piece of the distal cervical tissue (incl. the tumor) is resected. The rest of the cervix is left intact. The operation is performed via the vagina, under local or general anesthesia. After a conization a woman can still become pregnant, as the rest of the cervix and the uterus are left intact.

With more advanced stage and larger cervical cancers, a conization is insufficient. A limited number of patients may be treated with a surgical procedure called a trachelectomy, where a larger part of the cervix is removed. Again, this will make pregnancy an option for the younger patients.

The most advanced form of surgery is a hysterectomy, where the cervix and uterus are removed along with adjacent connective tissue and lymph nodes. The procedure is performed under general anesthesia via the vagina, or through an abdominal incision. 

The abovementioned surgical procedures are all curatively intended, if they are performed by skilled surgeons on sufficiently and correct  staged patients.

Chemotherapy and antibody therapy

For recurrent or disseminated cervical cancer, where curative treatment is not an option, chemotherapy and antibody treatment can be given intravenously to decrease tumor burden and alleviate symptoms for the patients. The addition of antibody therapy to combination chemotherapy, have demonstrated good effects, and can hopefully prolong life for treated patients. 

The antibody targets cancer cells by blocking their blood supply and thereby inhibiting tumor growth.

The combination treatment can be associated with side effects, and it is important to discuss the risks and possible treatment options with your oncologist prior to starting treatment.

Radiation Therapy

Radiation therapy uses high-powered energy beams (usually fotons) to destroy and kill cancer cells. The cervical tumor and uterus etc. is irradiated from the outside through the skin (external beam radiation therapy), or from the inside through the vagina (brachytherapy). In a range of patients a combination of the two modalities is recommended for sufficient effect.

During radiation treatment care is taken to protect the surrounding normal tissue such as bladder, rectum, bowel, kidneys etc. However, it is often unavoidable that a limited dose affects the surrounding tissue, and consequentially results in side effects of varying degree.

The side effects may be urinary problems, diarrhea, inflammation of the mucous membranes in the vagina, bladder, rectum and bowel, as well as nausea, discomfort/pain, development of scar-tissue in the pelvic area (fibrosis), and swelling af the leg(s) due to lymphoedema. Brachytherapy can result in shortening and hardening (due to fibrosis) of the top of the vagina, resulting in sexual disabilities.

Always discuss the risks and possible treatment options with your radiation oncologist prior to commencing your treatment.

When radiation therapy is combined with chemotherapy as treatment for locally advanced cervical cancers (usually stage 2-3), it is referred to as chemoradiation treatment. It may also be given following surgery for a group of high risk patients to decrease their risk of recurrence of cancer.  

Making Decisions About your Care

The choice of therapy for your cancer is an individual decision, and many factors are taken in to consideration, when your doctor(s) discuss the best option(s) with you. These include the type, size and location/spread of the tumor, as well as your age and general health status. 

We recommend, that you have a thorough discussion with your doctor(s) about the results upon your diagnosis, the treatment-plan and your chances of recovery (e.g. prognosis).

You are encouraged to include family and/or friends for participation in doctors appointments etc. for improving your/their understanding and remembrance of relevant information, as well as for emotional and physical support during appointments and treatments. 

Your doctor can give a detailed explanation of the various therapy options, and has knowledge of the possibility to participate in a clinical trial. Each patient is different and so is their wish upon information needed/wanted prior to making important decisions. 

Well designed and conducted clinical trials are essential to determine the effectiveness of a promising new drug or intervention. Many gynaecologic oncology departments have studies open for inclusion during the course of your cancer treatment. Talk to your doctor(s) about your thoughts regarding possible inclusion in a clinical trial now or in the future.

                                                                                                               (References; www.DGCG.DK, Kræft Klinik og sygepleje, FADL’s forlag 2019) 

Author: Kristine Madsen, MD, Deputy Medical Director NSGO-CTU

Privacy Policy for NSGO

NSGO treats personal information and complies with the laws and principles of good data processing practices. Therefore, we have adopted this Privacy Policy, which briefly describes how we treat personal information, so legal and transparent processing is ensured.

We are responsible for processing your personal information:

NSGO is the data controller and you can always contact the organization’s data protection officer:

Kristine Madsen

Nordic Society of Gynecologic Oncology – Clinical Trial Unit
Copenhagen University Hospital
Department of Oncology, 9431
Blegdamsvej 60
DK-2100 Copenhagen
Office phone: +45 35 45 33 78
fax: +45 3545 2898
nsgo-dpo.rigshospitalet@regionh.dk

We treat the following personal information about members:

  • General personal information: For example, contact information such as name, work address, work phone number, private phone number, date of birth, email address, country, work title, date of membership, date of membership termination and cv in relation to membership application. Parts of credit card number via Epay and, if applicable, Bank account number for reimbursement purposes. When applicable, Board Members may be asked to give NSGO copies of other personal documents (for example passport or tax bill) in relation to the Danish Laundering Act.
  • Other information: For example, positions of trust, board membership and other duties in relation to the organization.

We collect personal information from:

Usually we will get the information from you, when you register to become a member of NSGO and when you apply for reimbursements or pay your membership fee

The organization’s legal basis to process personal information:

  • That we as an organization have a (legitimate) interest in processing your information
  • That it is necessary for us to fulfill an agreement with you
  • You have agreed that we can process your information via becoming a member of the

The purpose of processing personal information:

  • That we can run the organization’s activities, including planning, implementing and following up on them
  • To invite to vote for Board and President Elect elections
  • To distribute newsletters
  • To comply with legislation
  • To deliver services, in the form of the possibility to participate in the Annual Meeting, Investigator Meeting and if applicable Strategic Meetings, Board Meetings, Scientific Committee Meetings, Foundation Meetings.
  • To notify members about other Gynecologic Cancer Managing your relationship with the organization
  • To handle your membership rights
  • For you to fulfill your obligations as a member of the organization, including paying the membership fee, etc.
  • Being able to display situation images from a specific event in the organization for instance from NSGO Annual Meetings
  • To maintain historical value data for statistics and the like

Consent:

When you become a member, we have a legal basis to process your personal information for the (legitimate) interest of the organization. However, it may happen that we judge it necessary to obtain your written consent for other purposes. In that case you will have the opportunity to voluntarily agree, and you may withdraw it at any time by notifying us.

Dispatch of your personal information:

We do not disclose information about you to anyone outside the organization without your consent, however, it should be noted, that if you e.g. accept an invitation to a meeting, your personal information might be forwarded to the meeting location or the meeting organizer. Only personal information relevant for the 3rd party will be disclosed in these circumstances.

Storing and deleting your personal information:

For historical reasons and as your details might be saved in old attendance lists, email correspondence and minutes from meetings, we cannot promise that all personal information about you will be deleted, if you terminate your membership.

Your rights:

You have a number of rights via the General Data Protection Regulation (GDPR):

  • The Right to Information (to be informed what information we process about you)
  • The Right to Rectification (to have false information about you corrected)
  • The Right to Restriction of processing (under certain conditions, to have the processing of your data restricted)
  • The Right to Object (to object to your information being used for wrong purposes)

You may make use of your rights by contacting us. If you submit a request to have your personal information corrected or deleted, we will investigate whether the conditions are met and, in that case, make changes or deletions as soon as possible and, if applicable, also notify our data processors to do so.

You can file a complaint with the supervisory authorities – The Danish ‘Datatilsynet’ – About processing your personal information (www.datatilsynet.dk).

Revision of Privacy Policy:

We reserve the right to change the organization’s privacy policy. When we change privacy policy, we also change the date and version number at the bottom of this document. In case of significant changes, you will receive a notification.

The current privacy policy is always available on our website.

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Privacy Policy for NSGO-CTU

NSGO-CTU treats personal information and complies with the laws and principles of good data
processing practices. Therefore, we have adopted this Privacy Policy, which briefly describes how we treat personal information, so legal and transparent processing is ensured.

We are responsible for processing your personal information:

NSGO-CTU is the data controller and you can contact the organization’s data protection officer:

Kristine Madsen

Nordic Society of Gynecologic Oncology – Clinical Trial Unit
Copenhagen University Hospital
Department of Oncology, 9431
Blegdamsvej 60
DK-2100 Copenhagen
Office phone: +45 35 45 33 78
fax: +45 3545 2898
nsgo-dpo.rigshospitalet@regionh.dk

We treat the following personal information about personnel participating in NSGO-CTU trials:
• General personal information: For example; contact information such as name, work
address, work phone number, date of birth, email address, country, work title, date of start
of participation and termination in a trial and, if applicable, CV, GCP certificates, records of
training and other qualification data.
• If applicable, financial disclosure forms and/or Bank account number for reimbursement
purposes.

We collect personal information from:
• We will ask you to provide us the information yourself, when you in decide to take part
in NSGO-CTU trials.
The organization’s legal basis to process personal information:
• That we as an organization have a (legitimate) interest in processing your information, for
example to secure your qualifications in handling the care of the participants in a trial.
• That it is necessary for us to fulfill an agreement with your employer
• You have agreed that we can process your information via signing the delegation log.
The purpose of processing personal information:
• The participation of an investigator or of other individuals in a clinical trial which is being
conducted according to the principals governing clinical research as set out in the
Declaration of Helsinki and with the acceptance of all involved Regulatory Health
Authorities and involved Ethical Committees, requires collection, recording, storage,
transfer and/or other use of personal data (personal data processing).
• Communicate regarding studies.
• To handle payments and reimbursements.
• To comply with legislation.
• To deliver services, in the form of the possibility to participate in the Annual Meeting,
Investigator Meeting.
• To be able to give you access to IT systems, databases, eCRFs etc. related to the functioning
of each individual trial.

Consent:
When you decide to take part in a NSGO-CTU trial NSGO-CTU either makes a contract with you or
your employer where terms and conditions are described, or if you put your name on the
Delegation Log of a trial, you agree to the information described in this Privacy Policy.
However, it may happen that we judge it necessary to obtain your written consent for other
purposes. In that case you will have the opportunity to voluntarily agree, and you may withdraw it
at any time by notifying us.
Be aware that there are legal bases for certain forms of processing of your data for the abovementioned purposes and that your consent is the only legal basis for other forms of processing.

Dispatch of your personal information:
Depending on your role in a trial, your personal information might be shared with personnel at
other sites, monitors, group staff in other countries, NSGO-CTU office staff, members of NSGO,
CRO staff, Ethics Committees and Competent Authorities, both in Europe, but also in countries
outside the European Economic Area (for example the US). If your data (personal information) has
been transferred, they will be subject to the data protection legislation of the respective country,
also if a less severe data protection law should exist.
We do not disclose information about you to anyone outside the organization without the above
consent, however, it should be noted, that if you e.g. accept an invitation to a meeting, your
personal information might be forwarded to the meeting location or the meeting organizer. Only
personal information relevant for the 3rd party will be disclosed in these circumstances.
Furthermore, your data can be transmitted to public databases for registration, as well as
publication of a trial and your data can be stored and published in those databases.
Storing and deleting your personal information:
For historical reasons and as your details might be saved in old attendance lists, email
correspondence and minutes from meetings, we cannot promise that all personal information
about you will be deleted, when you end your participation in a study. In general, all information
about a trial is deleted at least 20 years after end of study.

Your rights:
You have a number of rights via the General Data Protection Regulation (GDPR):
• The Right to Information (to be informed what information we process about you)
• The Right of Access (to get a print of the information we process about you)
• The Right to Rectification (to have false information about you corrected)
• The Right to Erasure (to delete information we process about you, however, information
already received cannot be deleted)
• The Right to Restriction of processing (under certain conditions, to have the processing of
your data restricted)
• The Right to Object (to object to your information being used for wrong purposes)

You may make use of your rights by contacting us, however, the legality of the processing carried out
prior to e.g., a withdrawal will not be affected. If you submit a request to have your personal
information corrected or deleted, we will investigate whether the conditions are met and, in that
case, make changes or deletions as soon as possible and, if applicable, also notify our data
processors to do so.

If you do not believe that NSGO-CTU handles your data correctly, you can file a complaint with the
supervisory authorities – The Danish ‘Datatilsynet’ – About processing your personal information
(www.datatilsynet.dk).

Revision of Privacy Policy:
We reserve the right to change the organization’s privacy policy. When we change privacy policy,
we also change the date and version number at the bottom of this document. In case of significant
changes, you will receive a notification.

The current privacy policy for NSGO-CTU is always available on our website.

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