Cervical carcinoma

Aim to detect pre-invasive disease. ~1600 women die yearly of cervical cancer in the UK. Many have had no smear, but this is changing: 

Causes

The main cause is human papilloma virus (eg HPV 16, 18, and 33). Type 16 is associated with squamous carcinoma, type 18 with adenocarcinoma. Vaccines are effective (if combined with screening this is a cost-effective preventive strategy;also, if given locally to the uterus, CIN 1, 2 & 3 can regress). Prolonged Pill use is thought to be an important co-factor (may increase risk 4-fold in those +ve for HPV DNA). Other risk factors: high parity; many (>4) sexual partners or a partner with many other partners (especially if that male is uncircumcized); early first coitus; HIV; other STDs; smoking.

Management of abnormal smears

Either a repeat smear or colposcopy and biopsy are needed, depending on likelihood of the smear reflecting CIN III or small volume invasive disease (<3mm).

Abnormal smears cause anxiety and guilt. Explain. Give support.

Treatment of pre-invasive carcinoma

Examine the cervix by colposcope ( binocular microscope). Abnormal epithelium has characteristic blood vessel patterns and stains white with acetic acid. Take punch biopsies for histology. CIN is destroyed by cryotherapy, laser, cold coagulation, or large loop excision of transformation zone (LLETZ). These give ~90% cure rates with one treatment. She needs annual smears for at least 10 years. If the squamocolumnar junction cannot be seen, or if small volume invasive carcinoma is found on histology, the abnormal tissue is removed by cone biopsy, which may be curative. Colposcopy does not detect adenocarcinoma (it usually lies within endocervical canal).

Invasive disease

Most are squamous cancers. 15-30% are adenocarcinomas (from endocervical epithelium, with unknown risk factors), especially affecting women under 40. Spread is local and lymphatic.

• Stage I tumours are confined to the cervix.
• Stage II have extended locally to upper 2/3 vagina; IIb if to parametria.
• Stage III have spread to lower 1/3 of vagina IIla; or pelvic wall IIlb.
• Stage IV have spread to bladder or rectum. IVb if spread to distant organs.

Most present in stages I or II.

Diagnosis

Overt carcinoma is rarely detected on a smear. Non-menstrual bleeding is the classic symptom. The early tumour is firm. It grows as a friable mass which bleeds on contact.

Treating invasive cancers

Stage Ia1 (microscopic lesions, invasion <3mm) may be treated by cervical conization in those wishing to preserve fertility, extrafascial hysterectomy for those with completed families.

Radical hysterectomy with pelvic lymphadenectomy or radiotherapy is used for stage Ia2 (microscopic, invasion 3-5mm depth <7mm horizontally) disease and some stage Ib1 (macroscopic, tumour <4cm). Chemoradiation is the gold standard for most stage Ib, II or bulky stage II disease. It is also used for stage III and IV disease.

Use of chemotherapy in advanced and recurrent disease is palliative.

The main chemotherapy agent is cisplatin. Pelvic exenteration is sometimes used in stage IVa disease. Cure rates for stages I (80% 5-yr survival) and II (60%).

Radiotherapy causes vaginal stenosis: so encourage intercourse within 2 months of treatment (+lubricant). Follow-up: annual smears. Smears are of no value after radical radiotherapy. Terminal problems are pain, fistulae, and GI/GU obstruction.

CIN I = mild dysplasia; CIN II = moderate dysplasia; CIN III = Severe dysplasia/carcinoma-in-situ

 

The table above shows comparative terms and the recommended action. The third column, headed histology, shows the percentage of smears in each Papanicolaou (cytological) class which have more serious lesions (CIN II or III) on histology. With inflammatory smears, swabs should be taken and any infection treated. 6% of inflammatory smears have serious pathology, hence the recommendation for colposcopy if inflammation persists.

 

Borderline nuclear abnormality (BNA)

implies doubt as to the neoplastic nature of any change. Re-smearing (eg at 3-6 months), or colposcopy (eg after 2 smears with BNA, if numbers of affected cells are static over time). Such colposcopy should be seen as part of the screening process, and need not prompt treatment. This goes part of the way to avoid false negatives, as well as to avoid the problems of overtreatment.

In the UK, 6×10⁶ smears are done per year on women up to 65yrs old, and cervical cancer deaths have fallen by 15% in recent years to <1900/yr. The incidence of cervical cancer in England and Wales fell by 42% between 1988 and 1997. 

Cervical screening is thought to prevent 5000 deaths/year in the UK. 2.4% of smears show mild dyskaryosis, and 2.2% have BNA. As most of these will eventually need colposcopy because of further smear results and 48% can be expected to have CIN II or III, and as a significant proportion may be lost to follow-up, it is suggested that immediate colposcopy with directed biopsy is indicated. However,[bomb] this would be very expensive, and anxiety-provoking. The cost in the USA of adopting this policy is ~$1 billion, and the benefits are uncertain as no randomized trials have been done.

Terminology used in reporting smears changed in the 1980s, and different countries use different nomenclature eg the Bethesda system.