Cervical cancer

Notes

Overview

Cervical cancer is a common malignancy whose aetiology is intimately related to human papillomavirus.

In the developing world cervical cancer is the second most common cancer in women. In the UK it is the most common cancer in women younger than 35.

It can occur in women, transgender men (with retained cervix) and non-binary individuals (assigned female at birth).

Cervical screening has helped to prevent cervical cancer by diagnosing and treating pre-malignant lesions. However unfortunately attendance to screening fluctuates and has been falling recently prompting a number of national campaigns to combat this.

Uterine anatomy

The cervix is the 'neck' of the uterus. It has an external os, continuous with the vaginal canal, and an internal os continuous with the uterine cavity. Between the two os lies the endocervical canal which is lined by simple columnar epithelium. The ectocervix is the vaginal canal facing portion of the cervix and is lined by stratified squamous non-keratinised epithelium.

Epidemiology

There are around 3,200 cases of cervical cancer in the UK each year.

In 2017, cervical cancer accounted for 2% of cancers and was the 14th most common cancer in women. In 2015 - 2017, incidence was highest in women aged 30 - 34. 

It is projected that incidence will decrease in coming decades as a result of the HPV vaccines.

HPV

Human papillomavirus (HPV) is implicated in the development of approximately 99.7% of cervical cancers.

HPV is a common virus that is normally sexually transmitted. It is estimated that 50-80% of sexually active women will have a HPV infection in their lifetime. Around 40% will be infected in the first two years of being sexually active.

There are more than 100 types though less than 20 have been strongly linked to cervical cancer (so called high risk HPV). The two most important subtypes are HPV 16 and 18 - they are responsible for 70-75% of cervical cancers.

The majority of infections are asymptomatic and resolve spontaneously. However they may lead to oncogenic changes and cervical cancer.

Non-cancer causing strains (or at least the evidence associating them with cancer is limited) HPV 6 and 11 are responsible for genital warts.

Risk factors

Certain risk factors increase the risk of cervical cancer in those with HPV infections.

  • Missed screening
  • Smoking
  • High parity
  • Family history
  • Combined oral contraceptive
  • HIV
  • Immunosuppression 

In daughters of women treated with diethylstilbestrol (DES) there is an increased risk of clear cell adenocarcinoma of the cervix. DES was a synthetic oestrogen used in the 1940’s to the 1970’s to prevent premature labour and miscarriage and was later found to be associated with cervical cancer.

Types

The most common type of cervical cancer is squamous cell carcinoma.

Around 70-80% of cervical cancers are squamous cell. The second most frequent cell type is adenocarcinoma, responsible for around 10% of cases. Other rarer causes include small cell cancer and lymphoma.

Types of cervical cancer

Adenocarcinomas tend to develop within the endocervical canal and are often diagnosed at more advanced stages.

Clinical features

The clinical features of cervical cancer are non-specific.

Features are similar to those seen in other gynaecological malignancies and infections. Features that may be seen in cervical cancer include:

  • Intermenstrual bleeding
  • Post-coital bleeding
  • Post-menopausal bleeding 
  • Malodorous discharge
  • Blood-stained discharge
  • Pelvic pain
  • Dyspareunia

On examination a malignant appearing cervical lesion may be apparent. On occasion patients will present with features of advanced disease - this can include fistulisation to surrounding structures including the bladder and bowel.

Referral

Women with suspected cervical cancer should be referred on an urgent (two-week wait) suspected cancer pathway.

The cervical cancer screening programme is the most common referral pathway. For more information on routine screening, see our note on Cervical cancer screening.

In addition NICE NG 12 Suspected cancer: recognition and referral advise urgent (two-week wait) referral if on examination the appearances of the cervix are concerning for cancer.

Symptoms of cervical cancer are non-specific and often similar to other gynaecological malignancies. Additional prompts for referral include:

  • Unexplained cervical symptoms (including discharge)
  • Postmenopausal bleeding:
    • If not on hormone replacement therapy (HRT)
    • Persistant/unexplained bleeding 6 weeks after stopping HRT
  • Premenopausal bleeding:
    • Persistant bleeding and polyp, ectropion, cervicitis, or warts and any infection treated
    • Persistent intermenstrual bleeding

Other reasons for referral includes patients with suggestive features who have not attended screening, have bleeding > 3 months, change in symptoms or failure of contraception to regulate bleeding.

Investigations

Colposcopy +/- biopsy is the key investigation in the diagnosis of cervical cancer.

Bloods

  • FBC
  • UE
  • LFT

Colposcopy 

Colposcopy allows optimal and magnified visualisation of the cervix and for biopsies to be taken. 

Imaging

CT, MRI and PET may all be used to assess disease burden and spread. 

FIGO staging

The International Federation of Gynecology and Obstetrics (FIGO) staging system is commonly used to stage cervical cancer.

Stage 1

IA: Invasive carcinoma diagnosed only by microscopy, with maximum depth of invasion <5mm

  • IA1: Measured stromal invasion <3 mm in depth
  • IA2: Measured stromal invasion >/=3 mm and <5 mm in depth

IB: Invasive carcinoma with measured deepest invasion >/= 5 mm(greater than Stage IA), lesion limited to the cervix uteri

  • IB1: Invasive carcinoma >/= 5 mm depth of stromal invasion, and <2 cm in greatest dimension
  • IB2: Invasive carcinoma >/= 2 cm and < 4 cm in greatest dimension
  • IB3: Invasive carcinoma >/= 4 cm in greatest dimension

 

Stage 2

IIA: Involvement limited to the upper two-thirds of the vagina without parametrial involvement

  • IIA1: Invasive carcinoma < 4cm in greatest dimension
  • IIA2: Invasive carcinoma >/= 4 cm in greatest dimension

IIB: With parametrial involvement but not up to the pelvic wall

 

Stage 3

IIIA: Carcinoma involves the lower third of the vagina with no extension to the pelvic wall

IIIB: Extension to the pelvic wall and and/or causes hydronephrosis or non-functioning kidney

IIIC: Involvement of pelvic and/or para-aortic lymph nodes, irrespective of tumour size and extent (with r and p notations)

  • IIIC1: Pelvic lymph node metastasis only
  • IIIC2: Para-aortic lymph node metastasis

 

​​​​​​​Stage 4

IVA: Spread to adjacent pelvic organs

IVB: Spread to distant organs

Management

Management is dependent on staging and patient wishes.

The aim is to achieve cure (if possible) or prolong disease and complication free life. Here we discuss the broad principles of management of cervical cancer. In advanced disease palliative care input can be essential.

Stage IA1 (microinvasive disease)

Large loop excision of the transformation zone (LLETZ) or knife cone biopsy can be used. The risk of lymph node metastasis is low and lymphadenectomy is rarely warranted. 

Simple hysterectomy may also be considered, particularly if preserving fertility is not an issue.

Stages IA2-IIA (early stage disease)

Stage IA2 have risk of spread to the pelvic and para-aortic lymph nodes. One option for treatment is a modified radical hysterectomy with lymphadenectomy.

Stage IBI and stage IIA less than 4cm are often treated with radical hysterectomy with lymphadenectomy.

In pre-menopausal women, ovarian conservation may be discussed and fertility sparing treatments can be considered if the patient has not completed their family. This will depend on exact staging and patient wishes.

For those with disease > 4cm, chemoradiation is the treatment of choice.

Stage IIB-IVA (locally advanced disease)

Chemoradiation tends to be the treatment of choice.

Stage IVB (metastatic disease)

Combination chemotherapy, single agent therapy and palliative radiotherapy may all be used.

Prevention

There are three key elements in prevention; vaccination, screening and safe sex.

In addition standard advice on leading a healthy lifestyle is appropriate. Smoking cessation reduces risk of cervical cancer.

HPV Vaccine

The HPV vaccine requires two doses and is offered to both boys and girls. The first dose is given at ages 12-13 whilst the second is given 6-12 months later.

Currently Gardasil is used, a vaccine that protects against four subtypes of HPV: 6, 11, 16, 18. As described above, HPV 16 and 18 are responsible for around 70% of cervical cancer cases, whilst HPV 6 and 11 are implicated in the development of genital warts.

Screening

The NHS Cervical Screening Programme (NHSCSP) is a key to reducing the rate of invasive cancers. For more information see our note.

Safe sex

Practical information should be given on safe sex. Using barrier methods of contraception (i.e. condoms - note that these do not eliminate risk) results in reduced exposure to HPV, as does having fewer partners.

It is important to understand that many patients will want an active sex life. Provide information and support for adults and young people to make decisions that are best for them.

Prognosis

Prognosis is dependent on stage at diagnosis, 96% diagnosed at the earliest stage survive a year or more.

  • 81.1% of women survive one year or more after diagnosis
  • 61.4% of women survive five years or more after diagnosis

Those who are younger at diagnosis have improved survival. About 90% of women aged 15-39 survive five years whilst just 25% over the age of 80 will.

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