Provincial Health Services Authority (PHSA) improves the health of British Columbians by seeking province-wide solutions to specialized health care needs in collaboration with BC health authorities and other partners.
Updated 8 August 2008
Cancer of the uterine cervix is the ninth most common cancer in BC women with an incidence rate of 9.8 per 100,000. Over 80% of all cervical cancer cases are squamous cell carcinomas arising in the ectocervix with further 17% being adenocarcinoma or adenosquamous carcinoma arising in the endocervical canal. The incidence rate has been steadily falling for several decades with an average annual rate of decline of about 2% (National Cancer Institute of Canada, 1998). Cervical cancer responds well to treatments, resulting in a 5-year relative survival of about 74%.
Human papillomaviruses (HPV) infection, particularly with one of several particular virus subtypes, is the major factor causally associated with cervical cancer. Several studies have observed relative risks ranging from 4 to 40 fold (Kelsey and Whittemore, 1994). There is evidence of positive relationships between cervical cancer risk and early age of first marriage, early age of pregnancy, greater number of sexual partners, as well as early age of first intercourse. The relationship with lifetime number of sexual partners appears weakened when HPV infection is taken into account.
Higher risks of cervical cancer have been observed for long-term or high-intensity smokers. However, in many recent studies, the effect of smoking has practically disappeared when HPV infection is taken into consideration.
HIV infection in women also appears to elevate risk of cervical cancer.
The early detection of precancerous lesions, through the Papanicolaou (Pap) smear, can basically prevent invasive squamous cell carcinoma of the cervix. This test was introduced in Canada in the mid-1960s and is widely used in BC. A recent Canadian workshop (Miller et al, 1991) recommended re-screening every three years, after two annual normal smears, for women age 18-69; in the context of an organized screening program.
Prevention of transmission of HPV infection appears to be unfeasible currently. Condom use cannot completely prevent the spread of HPV genital infections because the genital HPV infections are not restricted to the penile skin (Kelsey and Whittemore, 1994).
There is now a vaccine which protects against 2 types of Human Papillomaviruses that cause most cervical cancers.The vaccine is recommended for girls and women between the ages of 9 and 26 years before they come in contact with HPV. The vaccine may also benefit women who are sexually active and have not yet been infected with HPV. The vaccine prevents HPV infection but it does not get rid of it once the infection occurs.
In women who have never been infected with HPV, the vaccine:
For more information call your local Public Health Unit or speak to your Family Physician. You can also go to the links above.
National Cancer Institute of Canada. Cancer Statistics, 1998. NCIC, Toronto.
Kelsey J, Whittemore AS. Epidemiology and primary prevention of cancers of the breast, endometrium and ovary: a brief overview. Ann Epidemiology 1994;4:89-95.
Miller AB, Anderson G, Brisson J, et al. Report of a national workshop on screening for cancer of the cervix. Can Med Assoc J 1991;145:1301-1325.
Updated 4 September 2013
Screening ProgramScreening for Cancer of the Cervix: An Office Manual for Health Professionals
Handouts & MaterialsThe following recommendations have been approved for women who are or have been sexually active:
After three negative Pap smears (reported satisfactory for evaluation) at one-year intervals, screening should be continued every 24 months, until age 69.
Also see Endometrium - Screening
Cervical cancer continues to be a major problem within the province. Although significant strides have been made in the reduction of both the incidence and mortality for clinical carcinoma of the cervix, a continued effort is necessary to maintain and improve these results. High risk groups identified in our province continue to be First Nation women, recent immigrants and those women who have never participated in screening programs. Regular Pap smear screening continues to be the most effective method to try and diagnose lesions which are in a pre-clinical and pre-invasive state where the opportunity for cure is uniformly high.
Cervical Pap smears remain the most effective method of identifying the patient with possible preinvasive or preclinical cervical neoplasia. Pap smears taken in the presence of bleeding, spotting or discharge are often difficult to interpret and may be unreliable. It is recommended that women who have 3 consecutive negative smears and who have never had an abnormal Pap smear be screened every 2 years. Women who have a history of prior abnormal smears (CIN) should continue with annual smears. Refer to 4.3 above for Pap smear guidelines.
The optimum time for taking smears in the pre-menopausal women is in mid-cycle. However, for practical purposes this is not always possible, but if there is difficulty in obtaining good smears in these individuals then repeat smears should be scheduled for this interval. There is no single sampling device which is adequate for all cases, but in the vast majority of individuals the standard wooden Ayres spatula is satisfactory. Individuals who are post-menopausal or in whom the squamocolumnar junction may be placed within the endocervical canal because of previous surgery or other factors, may require sampling with an endocervical cytobrush or other devices to obtain specimens from this area. If a cytobrush is used immediate fixation with cytospray is required. Conversely, individuals who have a large area of columnar epithelium on the ectocervical surface need to have sampling from the peripheral margins of this transformation zone. If an endocervical specimen is taken as well as the standard scrape both specimens should be placed on the same slide using the opposite half of the glass slide.
Simple lack of endocervical cells in the Pap smear report does not necessarily mean that the smear in itself is inadequate. In older individuals where difficulties may be present in obtaining good quality smear, particularly in the post-menopausal women or women who have undergone radiation treatments to the pelvis, often a short course of topical or oral estrogen therapy will thicken the epithelium and produce a much better quality smear for evaluation.
It should be emphasized that an office punch biopsy should be taken of any clinically suspicious or so-called "target lesion" noted at the time of pelvic examination.
The recommended method of investigation of patients with abnormal Pap smears where no target lesion exists is with colposcopy. Regional colposcopy clinics have been established throughout the province for this purpose and their locations are listed in Appendix V. It is to be noted that patients are referred to the regional clinics for assessment, not to the individual performing colposcopy at these locations. Patients are then returned to the original physician for decision as to further management and disposition based on the results and findings of the colposcopic examination. Private practice office colposcopy is not part of the BCCA Provincial Colposcopy Program and as such is not subject to the Agency's Quality Control Program.
HISTOLOGICAL CLASSIFICATION OF INVASIVE CERVICAL CARCINOMAS
(synonyms: malignant carcinoid tumours, neuroendocrine carcinomas, arygyrophilic carcinomas, apudomas)
*Most carcinomas referred to in the older literature as "small cell carcinomas" would, by current criteria, likely be placed in the category of small cell carcinoma.
Microscopic description for cervical tumours should include the following features:
Click image for larger version
Following biopsy confirmation of carcinoma of the cervix, history and physical examination and staging, the following lab and radiological studies should be done:
Referral, however, should not be delayed.
Updated 17 May 2006
Koilocytosis on a Pap smear is evidence of an HPV infection, but does not mean that a patient needs routine colposcopic assessment. Often this change will be in conjunction with mildly dyskaryotic cells. If the problem persists then colposcopic examination is recommended. If evidence of a clinical HPV lesion (condyloma is noted on the cervix or upper vagina) is noted, then colposcopic examination may help the assessment of the severity and location of lesions.
Patients in whom the initial cytological examination shows mild dysplasia are generally followed by repeat smear on a six month basis. Persistence or progression of these lesions should lead to treatment by appropriate methods. In young women with persisting dysplasia of this type and ectocervically located lesions, cryotherapy or laser therapy may be employed to eradicate the lesion.
Patients with Pap tests showing moderate dyskaryosis or CIN II should be evaluated by colposcopy. Moderate dysplasia is usually treated with cryotherapy or laser therapy.
No distinction is made between these two lesions with regard to basic treatment recommendations.
A variety of treatment methods are available for the management of these lesions. A decision as to the appropriate treatment method is made after consideration of several factors amongst which is the age of the patient and her desire for future pregnancies.
In women who have completed their families and in whom other gynecological conditions exist simple hysterectomy either by the abdominal or vaginal route remains an acceptable method of treatment with the lowest recurrence or new disease rates for this disorder. This method also precludes further cervical or uterine pathology.
In women who have not yet completed their families and in whom the colposcopic examination has been classified as satisfactory, i.e., visualizing the entire lesion squamocolumnar junction with good cytologic and colposcopic correlation, cryotherapy, electrosurgical loop excision procedures or laser therapy may be employed to eradicate the disease focus. These methods have a negligible complication rate and will not adversely affect fertility or further reproductive function. In addition they have the advantage of being ambulatory treatment methods without the need of anaesthesia and minimal analgesia. For women in whom the lesions extend into the endocervical canal or in whom the colposcopic examination is unsatisfactory, cervical conization becomes the recommended method. We recommend cold-knife conization rather than loop electrosurgical techniques if diagnostic cone biopsy is needed because of the generally superior histological specimen with the former technique. If properly performed, cervical conization will have minimal effects on future reproductive function and will have a complication rate of less than five to ten percent. Patients who have undergone treatment with surgical conization in whom questionable margins or incomplete excision has been reported required meticulous follow-up. Smears and endocervical curettage may help ensure persisting disease or more advanced pathology does not go unrecognized. Routine Pap smear follow-up for these individuals may be somewhat less than ideal as it may be difficult to obtain good quality smears from the area at greatest risk.
The treatment of these lesions will be based on a thorough histologic examination of a properly obtained cone biopsy specimen. It is strongly recommended that all these patients have their slides reviewed at the BC Cancer Agency and that the patient be presented to the Gyne Disposition group for a treatment recommendation.
Patients presenting with Stage Ia microinvasive carcinoma with 3 mm or less of invasion without lymphatic vascular space involvement, conservative treatment with simple hysterectomy will be recommended. Occasionally, for very early disease removed with a satisfactory margin, conization may be considered adequate therapy, if fertility preservation is an issue.
If invasion is 3 mm or less and lymphatic vascular space invasion is present, treatment recommendation will be made after slide review and may vary from conservative to radical therapy.
In the case of adenocarcinoma, the need for further treatment will be individualized depending upon the extent of the disease. Therapy will be tailored accordingly and will range from cone biopsy only to radical hysterectomy with lymph node dissection.
In the case of patients with lesions exceeding 3 mm in depth, Stage Ia2, radical treatment will be required. This will usually be surgical, including treatment of the nodes. If the patient is not a surgical candidate, then radical radiotherapy would be used with a combination of external beam treatment plus intracavitary therapy.
When simple hysterectomy is inadvertently performed in the face of invasive carcinoma, post operative radiotherapy will be recommended. Post operative radiotherapy will also be recommended following radical hysterectomy in the face of poor prognostic factors
The treatment of patients with Stage Ib and IIa tumours is highly individualized depending on various specific histologic and clinical findings. Patients with tumour diameter <4 cm will be treated with either radical surgery or primary radiotherapy. Radiotherapy usually involves intracavitary insertions as well as external beam radiation treatment.
Radical hysterectomy and pelvic lymphadenectomy may be considered as primary therapy in the following situations:
Patients not fulfilling this criteria will be treated with primary radiotherapy.
In the case of patients treated surgically and in whom the pathologic specimen review reveals metastatic tumour within lymph nodes or positive surgical margins, lymphatic invasion, or a deeply invasive lesion, external beam therapy to the pelvis will usually be recommended after discussion at the gyne disposition meeting.
Lesions will be managed with external radiation treatment delivered to the pelvic region. Following external radiation treatment the patients undergo pelvic examination and, if the disease has regressed centrally, the treatment is completed with two intracavitary cesium insertions one week apart. However, if significant parametrial or side wall disease persists, instead of intracavitary treatment, further external beam boost treatment is delivered . If disease persists after radiotherapy further surgery may be considered.
Adenocarcinomas of the cervix are treated in the same manner as the more common squamous carcinomas.
This is an uncommon variant of cervical carcinoma which, like lung small cell, is usually systemic in spread and has a much worse 5 year survival. All patients need urgent chemotherapy +/- radiotherapy to the pelvis and para-aortic regions to try to improve both local and systemic control. Definitive surgery is not recommended, and urgent referral is advised.
Recent results from each of five randomized phase III trials show an average overall survival advantage for cisplatin-based therapy given concurrently with radiation therapy. Although the trials vary somewhat in terms of stage of disease, dose of radiation, and schedule of cisplatin and radiation, they all demonstrate significant survival benefit for this combined approach. The risk of death from cervical cancer would decrease by 30-50% by addition of concurrent chemotherapy treatment. Based on these results, we advise concurrent cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for the treatment of stage IB2 or larger cervical cancer or for those patients with involved pelvic or para-aortic lymph nodes. The protocol designation for this therapy is
GOCXCRT. It consists of weekly cisplatin at 40 mg/m2 weekly for five weeks during external beam radiation therapy.
Chemotherapy may be offered in the palliative setting of cancer of the cervix or as part of investigatory protocols. Our current standard is based upon cisplatin and etoposide (GOCXADV).
No data exist to show a contraindication for hormone replacement in cervical or vaginal cancer. Many of these patients are young and at high risk for estrogen deprivation related morbidity. It is the feeling of the group that these patients should be encouraged to take estrogen replacement. In the presence of a uterus we recommend continuous estrogen and progestogen with the estrogen at a moderate dose (0.625-1.25 mg Premarin) and the progestogen at a low dose (2.5 mg Provera). Histologic studies have shown that continuous therapy with combined estrogen and progestogen induces an atrophic bland endometrium. This regime may result in some initial bleeding for the first one to two months but in general the women are amenorrheic.
An alternative regime would be to use cyclical estrogen and progestogen. This has the disadvantage of inducing a withdrawal bleed in some patients who have not had total ablation of the endometrium. Hematometra may develop if there is cervical stenosis present leading to abdominal pain or a mass.
Recommendation: Continuous estrogen and progestogen, e.g.: Premarin; 0.625-1.25mg Provera 2.5 mg (note: these small doses of Provera do not seem to have the same deleterious effects on serum lipids as the higher doses.)
In the absence of a uterus there is no theoretical need for progestogen, therefore estrogen alone in usual doses is recommended.
Disease in the pregnant woman is generally managed as in the non-pregnant woman. If no suspicious target lesion is present on the cervix and Pap smears are positive, colposcopy should be performed. In the rare cases where colposcopy is unsatisfactory and the cytology positive, wedge or cone biopsy should be done, preferably in the middle trimester to minimize the risk to mother and fetus. Should invasive carcinoma be discovered in early pregnancy and thought to be unsuitable for primary surgical therapy, termination of the pregnancy is usually carried out with the method depending on the gestational age and is followed by radiotherapy. Certain patients with early stages of disease may be treated primarily with radical hysterectomy and pelvic lymphadenectomy. If the carcinoma is discovered in the later weeks of pregnancy, a delay in treatment is considered permissible to allow for viability of the fetus. For those patients diagnosed in the latter stage of pregnancy with a viable fetus, delivery by caesarean section is usually recommended although studies have not shown that vaginal delivery has produced a higher morbidity or decreased survival in patients delivered this way.
These treatment policies must be individualized as to the stage and extent of disease, gestational age and, in particular, the wishes of the patient.
Patients should be reminded that it is their responsibility to keep their recommended follow-up appointments. The objectives of the follow-up visits are as follows:
These objectives are best met by having the initial follow-up examination performed by the Agency medical staff. When appropriate, arrangements will be made for follow-up by the referring physician.
Note: Follow-up consists of general exam, pelvic exam, Pap smear. Other investigations such as CT can be requested as required for specific indications. Interpretation of Pap smears in the first 3 months after surgery or radiotherapy can be extremely difficult and not helpful. After this interval they can be performed.
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