# Obstetrics and Gynecology/Cervical Neoplasia
## Epidemiology

* Approximately 1/10000 women will develop cervical cancer.
* Cervical cancer accounts for 1.1% of all cancer deaths in women.
* Cervical cancer is diagnosed around ages 37 and 62, with a mean age of 52.

## Etiology, Pathophysiology, and Risk Factors

Squamocolumnar metaplasia is the basis for malignant transformation. However, this transformation is a normal process that begins at puberty and accelerates during pregnancy. Metaplastic cells are particularly vulnerable to HPV infection.
HPV infection breeds dysplasia, a process that occurs in only 1-3% of women infected with HPV, and finally progresses to invasive carcinoma.
** Note that >80% of sexually active women have been infected with HPV. However, the majority of these infections resolve spontaneously.

## Clinical Presentation and Diagnostic Approach

Cervical cancers typically present as
* An abnormal pap smear
* Abnormal bleeding
* Vaginal discharge, usually purulent
* Pain (a late symptom of advanced cervical cancer)
* Renal failure (a late symptom of advanced cervical cancer from bilateral ureteric obstruction

### Screening Guidelines for Cervical Cancer

The following guidelines are a summary of the screening guidelines for cervical cancer in Alberta, Canada.
* Screening should start at age 21 or 3 years after sexual debut, whichever occurs later.
* Perform yearly pap smears until 3 consecutive negative results, then move to every 3 years, unless woman is immunocompromised or past history of cancer/precancer.
* If at age 69 there have been no abnormalities, pap smears may cease.
Referral guidelines for cervical cancer screening results
* Continue routine screening if normal
* Repeat pap earlier: ASCUS/LSIL
* Refer for colposcopy: ASC-H/HSIL/Atypical Glandular Cells (AGC)/Adenocarcinoma in situ
* Refer to gynecological oncologist: invasive cancer

## Pathology, Histology, and Staging

Histologically, cervical cancer is split into three categories:
* Squamous cell: (80% of cervical cancers)
** These arise from the squamous epithelium in the transition zone of the cervix.
* Adenocarcinoma: (~20% of cervical cancers)
** These arise from the columnar cells in the cervical canal.
* Other: small cell neuroendocrine, Glassy cell carcinoma, Clear cell carcinoma, adenoma malignum
Cervical cancer spreads either
* Directly: typically along the parametrium, via the cardinal ligaments.
* Lymphatically: obtruator->internal iliac->common iliac->para-aortic

#### Staging

The staging of cervical cancer and the respective treatment options are presented in the table below.
| Stage | Classification | Treatment | 5 yr Survival |
| IA1 | Lesion less than 3mm deep, confined to cervix | Cone excision or radical hysterectomy | 100% |
| IA2 | Lesion between 3 and 5 mm deep, confined to cervix | Cone excision or radical hysterectomy, plus nodal dissection | 100% |
| IB1 | Lesion greater than 5mm but less than 4cm, confined to cervix | Radical hysterectomy, nodes, radiotherapy +/- chemotherapy | 85-90% |
| IB2 | Lesion greater than 4cm but confined to cervix | Radiotherapy +/- chemotherapy | 85-90% |
| IIA | Upper vagina with no parametrial involvement | Radiotherapy +/- chemotherapy, some will get surgery | 50-75% |
| IIB | Parametrial involvement | Radiotherapy +/- chemotherapy | 50-75% |
| IIIA | Lower third of the vagina with no sidewall involvement | Radiotherapy +/- chemotherapy | 30-50% |
| IIIB | Invasion of the pelvic wall and/or causes hydronephrosis | Radiotherapy +/- chemotherapy | 30-50% |
| IVA | Invasion of the bowel or bladder, but no extension past the true pelvis | Palliative radiotherapy +/- chemotherapy | 10% |
| IVB | Distant metastases | Palliative radiotherapy +/- chemotherapy | 10% |
Treatment decisions will be influenced by fitness and desire to have children.

## Management

See Staging table for management strategies.
If, at colposcopy, transitional zone lesions are found, the entire transition zone must be excised via loop electrosurgical excision procedure (LEEP). If colposcopy was unsatisfactory (i.e. unable to visualize entire lesion or adenocarcinoma in situ diagnosed), cone biopsy must be performed.
* Cone biopsy may result in cervical stenosis or incompetence.
If vaginal precancer is diagnosed at colposcopy, laser therapy can be administered.
Side effects for radiation are: Early: cystitis, diarrhea, pubic hair loss Late: radiation cystitis/proctitis, small bowel obstruction, vaginal stenosis, ovarian failure, and rarely fistula formation
For recurrent disease, surgery is the only option, with pelvic exenteration providing cure rates of 50-60%.