Pathologic types

This large squamous carcinoma (bottom of picture) has obliterated the cervix and invaded the lower uterine segment. The uterus also has a round
leiomyoma up higher.

Micrograph of a (cervical) adenosquamous carcinoma, a type of cervical cancer. H&E stain.

Potentially precancerous lesions

Cervical intraepithelial neoplasia, the potential precursor to cervical cancer, is often diagnosed on examination of cervical biopsies by a pathologist. For
premalignant dysplastic changes, the CIN (cervical intraepithelial neoplasia) grading is used.

The naming and histologic classification of cervical carcinoma percursor lesions has changed many times over the 20th century. The World Health
Organization classification[22][23] system was descriptive of the lesions, naming them mild, moderate or severe dysplasia or carcinoma in situ (CIS). The
term, Cervical Intraepithelial Neoplasia (CIN) was developed to place emphasis on the spectrum of abnormality in these lesions, and to help standardise
treatment.[23] It classifies mild dysplasia as CIN1, moderate dysplasia as CIN2, and severe dysplasia and CIS as CIN3. More recently, CIN2 and CIN3
have been combined into CIN2/3. These results are what a pathologist might report from a biopsy.

Thhese should not be confused with the Bethesda System terms for Pap smear (cytology) results. Among the Bethesda results: Low-grade Squamous
Intraepithelial Lesion (LSIL) and High-grade Squamous Intraepithelial Lesion (HSIL). An LSIL Pap may correspond to CIN1, and HSIL may correspond
to CIN2 and CIN3,[23] however they are results of different tests, and the Pap smear results need not match the histologic findings.

Cancer subtypes

Histologic subtypes of invasive cervical carcinoma include the following:[24][25] Though squamous cell carcinoma is the cervical cancer with the most
incidence, the incidence of adenocarcinoma of the cervix has been increasing in recent decades.[1]

• squamous cell carcinoma (about 80-85%[citation needed])

Non-carcinoma malignancies which can rarely occur in the cervix include

• melanoma
• lymphoma

Note that the FIGO stage does not incorporate lymph node involvement in contrast to the TNM staging for most other cancers.

For cases treated surgically, information obtained from the pathologist can be used in assigning a separate pathologic stage but is not to replace the
original clinical stage.

Staging

Cervical cancer is staged by the International Federation of Gynecology and Obstetrics (FIGO) staging system, which is based on clinical examination,
rather than surgical findings. It allows only the following diagnostic tests to be used in determining the stage: palpation, inspection, colposcopy,
endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and X-ray examination of the lungs and skeleton, and cervical
conization.

The TNM staging system for cervical cancer is analogous to the FIGO stage.

• Stage 0 - full-thickness involvement of the epithelium without invasion into the stroma (carcinoma in situ)
• Stage I - limited to the cervix
o IA - diagnosed only by microscopy; no visible lesions
 IA1 - stromal invasion less than 3 mm in depth and 7 mm or less in horizontal spread
 IA2 - stromal invasion between 3 and 5 mm with horizontal spread of 7 mm or less
o IB - visible lesion or a microscopic lesion with more than 5 mm of depth or horizontal spread of more than 7 mm
 IB1 - visible lesion 4 cm or less in greatest dimension
 IB2 - visible lesion more than 4 cm
• Stage II - invades beyond cervix
o IIA - without parametrial invasion, but involve upper 2/3 of vagina
o IIB - with parametrial invasion
 • Stage III - extends to pelvic wall or lower third of the vagina
o IIIA - involves lower third of vagina
o IIIB - extends to pelvic wall and/or causes hydronephrosis or non-functioning kidney
• IVA - invades mucosa of bladder or rectum and/or extends beyond true pelvis
• IVB - distant metastasis
• Presentation and risk factors
• The cervix is the inferior part of the uterus, which protrudes into the vagina. It is characterised by two types of epithelium: the endocervical
epithelium lines the uterus and superior part of the cervix, while the squamous epithelium is located distal to the endocervical epithelium. The
two cell types meet in a region known as the transformation zone, where most cellular abnormalities arise. Cervical cancer can develop from
the squamous cells or endocervical epithelium, but squamous cell carcinomas are the most common and account for 85-90 per cent of
cervical malignancies (Wright, 2001).
• The mean age of presentation is 54 years, although intraepithelial lesions are often diagnosed at a much earlier age suggesting long latency
between cellular abnormality and malignancy (Cannistra and Niloff, 1996).
• The most common presenting symptom of cervical cancer is abnormal bleeding, perhaps between periods, after intercourse or
postmenopause. This may be accompanied by offensive vaginal discharge. Risk factors include (Cannistra and Niloff, 1996):
• - Intercourse at an early age;
• - Multiple sexual partners (or a sexual relationship with a man who has had multiple partners);
• - Smoking;
• - Immunosuppression.
• Women who present before the cancer becomes too advanced have the best prognosis; cervical screening is effective because cervical
neoplasia has a long pre-invasive phase (Goodman and Wilbur, 2003).

(http://www.medicalnewstoday.com/articles/198468.php) Significant Advance Announced In Treatment Of Cervical Cancer

Dr Paul Symonds from the Department of Cancer Studies and Molecular Medicine has demonstrated that the use of a particular drug in collaboration
with radiotherapy gives significantly better results than radiotherapy alone.

The study used the case histories of 1,412 patients from 42 different cancer treatment centres which were collected in 2001-2 as part of an audit which
Dr Symonds led for the Royal College of Radiologists. This information included not only the treatment used but also follow-up notes which continued for
five years on average, indicating whether or not cancer recurred in the pelvic area.

The new research, supported by the Medical Research Council (MRC), studied the use of a drug called cisplatin, a platinum-based molecule which
directly affects the DNA strands within cells to cause controlled cell death or 'apoptosis'. It was already known that a combination of radiotherapy and
cisplatin was more effective than radiotherapy alone in curing cancer of the cervix but there was no reliable data on the long-term effects of the
combined treatment.

Working with colleagues in London and Manchester, Dr Symonds examined the long-term survival rates of patients after the treatment was complete.
Complex statistical analysis was used to eliminate variable factors in comparing radiotherapy with 'chemoradiotherapy'.

The results showed that the addition of cisplatin to radiotherapy treatment of cervical cancer reduces the likelihood of death by a full 23 per cent. This is
an important breakthrough and will be featured in the September issue of the publication Clinical Oncology alongside an editorial written by patients who
have recovered through the dual treatment and another editorial presenting a doctor's view.

Dr Symonds, who is also a Consultant Clinical Oncologist at Leicester Royal Infirmary, said: "The addition of cisplatin to radiation has literally saved the
lives of hundreds of women with locally advanced cancer in the east midlands.

"What the national audit has shown is that the addition of cisplatin improves survival. The addition of cisplatin in routine UK practice reduces the odds of
death by 23%. As this is curative treatment we can genuinely say that this is a reduction in the odds of death.

"This audit showed a marked improvement in 5-year survival of locally advanced cervix cancer compared to the last national audit of patients who were
treated in 1993. Moreover the UK results, as derived from a total of 42 centres (most district general hospitals) show that the results in the UK are now
compatible with the best international practice."

Source:
Dr. Paul Symonds
University of Leicester