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New Treatments for Cancer of the Cervix, Vulva, and Vagina

Herpes simplex virus infections increase that woman’s risk, women that are HIV positive are at much higher risk, those that are smokers, and those that are immunosuppressed or renal transplant patients for example that have an HPV infection are at much higher risk to go on to develop cervical cancer. There are at least 10-20 million women with HPV infections and cancer of the cervix.

Most patients with invasive cervix cancer we would hope would be picked up with an abnormal Pap smear, appropriately referred to a gynecologist. The patient would undergo colposcopy, which is nothing more than a 15 power dissecting binocular microscope.

The symptoms associated with cervix cancer is vaginal bleeding. It is one of the classic symptoms, although not oftentimes volunteered in my experience, but if you ask the patient, yes she has had bleeding after intercourse; it stops after a day or so and doesn’t reoccur.

The histology of cervix cancer is by and large, about 90% at least, squamous lesions. The other 10% are adenocarcinomas arising in the endocervical canal. Really for purposes of treatment and staging, we treat all the same with one little exception so that the pathologist will subdivide for you the biopsy. Saying this is a squamous cell lesion, it’s a large cell non-keratinizing.

In staging the patients with cervix cancer, the spread patterns are fairly monotonous and routine. Local spread to the vagina, the perimetria, the tissue next to the cervix and invading the cervical stroma are the initial routes of spread. From there into lymphatics and the lymphatics.

The staging system that we use and have modified over the years is a clinical staging system, rather than a surgical staging system that we use for endometrial cancer or for ovarian cancer. Cervix cancer is a clinically staged disease because most patients won’t undergo surgery as part of their treatment. They’ll be treated with radiation therapy and chemotherapy now.

If the patient has stage IIIb disease or if that’s disease extending sidewall to sidewall in the pelvis, she has about a 30% chance of having positive periaortic lymph nodes. And those are decisions that the radiation therapist is going have to make in consultation with others.

The radiation therapy plan that is conventionally used has been out there for a number of decades, 50 years or so. It’s usually a combination of external beam radiation therapy - either to the whole pelvis or an extended field of whole pelvis plus periaortic radiation - given in a fractionated fashion, approaching 4500 -5000 centigray to the whole pelvis. The periaortic chain tolerates about 4500 centigray before we start to talk about significant GI injury. In combination with the external beam radiation therapy that the patient gets at the initiation of her treatment.

Surgical management for the early stage patients. A radical hysterectomy is an operation that is done by GYN-oncologists. It’s not the operation that your local gynecologist would do. Because it requires more training, first of all, but more extensive resection; not only of the uterus and cervix but a portion of the upper vagina and all the perimetria, the tissue lateral to the cervix, to the pelvic sidewall. It’s thought of as an en block resection of the cervix and its perimetria, which is the lymphatic drainage, out to the sidewall combined with a lymphadenectomy.

Radiation therapy to treat an early stage patient is easily done in most patients. If the patient isn’t a surgical candidate, clearly radiation should be offered. There is really minimal immediate morbidity aside from the acute side effects of radiation with radiation proctitis, cystitis, radiation sickness. But all of that usually clears.

The next study to look at is the subsequent trial done by the GOG, which basically took the same group of patients. Radiation therapy plus one of three arms. Hydroxyurea remained in this protocol because the prior protocol 85 hadn’t been completely analyzed and mature by the time this trial got started. The next arm got 5FU, cisplatin and hydroxyurea, a fairly intense combination of sensitizers. And then the third arm received weekly cisplatin at 40 mg.