2.15.2 Treatment Options of Carcinoma in Situ
Treatment of carcinoma in situ includes following: LEEP
It is the removal of abnormal areas from the cervix using a loop made of thin wire powered by an electrosurgical unit. The loop tool cuts and coagulates at the same time, and this is followed by use of a ball electrode to complete the coagulation. LEEP aims to remove the lesion and the entire transformation zone. Cold knife conisation (CKC)
It is the removal of a cone-shaped area from the cervix; including portions of the outer (ectocervix) and inner cervix (endocervix). The amount of tissue removed will depend on the size of the lesion and the likelihood of finding invasive cancer. Cryosurgery
This treatment option eliminates precancerous areas on the cervix by freezing (an ablative method). It involves applying a highly cooled metal disc (cryoprobe) to the cervix and freezing the abnormal areas (along with normal areas) covered by it. Simple hysterectomy
It is the surgical removal of the entire uterus, including the cervix; either through an incision in the lower abdomen or through the vagina with or without using laparoscopy. The tubes and ovaries are not routinely removed, but they may be in postmenopausal women or if they appear abnormal. Simple hysterectomy is indicated for the treatment of early microinvasive cervical cancers in postmenopausal women and younger women who are not interested in preserving fertility. Radical hysterectomy
It is the most common surgery for early invasive cancers. This surgery removes tissue to the side of the uterus and often lymph nodes in the pelvis and around the aorta.
2.15.3 Treatment Options for Cervical Cancer at Various Stages
Early stages of cervical cancer are normally treated either surgically, including radical hysterectomy or pelvic lymph node dissection, or by a combination of chemotherapy and radiation (Rasty, Hauspy et al. 2009). For the small stage IA cervical cancers, surgery is the common treatment. Patients with locally advanced cervical cancers (stage IB2 – IVA) and patients with extra-cervical disease such as lymph node metastases, are primarily treated with concurrent chemoradiation comprising external beam irradiation and brachytherapy in combination with platinum-based chemotherapy (Movva, Rodriguez et al. 2009, Rasty, Hauspy et al. 2009, Klopp and Eifel 2011). Patients with stage IVB are not given the standard treatment, but are treated individually, usually with 5FU followed by surgery or conventional radiotherapy as for the other stages.
2.15.4 Treatment Options for Recurrent Cervical Cancer
Treatment of recurrent cervical cancer includes pelvic exenterating followed by radiation therapy combined with chemotherapy, chemotherapy as palliative therapy to relieve symptoms caused by the cancer and improve quality of life and clinical trials of new anti cancer drugs or drug combinations.
2.16 Prevention Using Vaccination
Two vaccines manufactured by recombinant DNA technology have been licensed globally and are available; a quadrivalent vaccine (Gardasil™ marketed by Merck) and a bivalent vaccine (Cervarix™ marketed by Glaxo Smith Kline) (Indian Academy of Pediatrics Committee on 2008).
Clinical trials with both vaccines have used efficacy against CIN-2/3 and adenocarcinoma in situ (AIS) caused by HPV strains contained in the concerned vaccine as primary end points (Indian Academy of Pediatrics Committee on 2008).
Gardasil is a mixture of L1 proteins of HPV serotypes 16, 18, 6 and 11 with aluminium containing adjuvant. Clinical trials with three doses at 0, 2 and 6 months in more than 16,000 women aged 16–26 years from five continents, including Asia, have shown 100% efficacy at a median follow-up of 1.9 years against types 16/18-related CIN-2/3 and AIS in the per-protocol analysis (women who received all three doses of the vaccine and who remained uninfected with vaccine HPV type at onset and for 1 month after completion of the vaccine schedule (Villa, Costa et al. 2005). This vaccine confers protection against both cervical cancer and genital warts.
Cervarix is a mixture of L1 proteins of HPV serotypes 16 and 18 with AS04 as an adjuvant. Clinical trials with three doses at 0, 1 and 6 months in more than 18,000 women globally has shown 90% efficacy against type 16/18-related CIN-2/3 and AIS at the 15-month follow-up in modified intention to treat analysis (included women who were at baseline negative for HPV DNA of vaccine type virus and who received at least one dose of the vaccine). Follow-up studies in a subset of participants over 4–5 years showed no evidence of waning immunity (Harper, Franco et al. 2004). In women already infected with a targeted HPV type, the vaccines do not prevent disease from that HPV type but protect against other vaccine types.
2.16.1 Side effects and Contraindications
The most common adverse reactions are local reactions like pain (mild to moderate) in 83%, swelling with erythema in 25% and systemic adverse effects such as fever in 4% of the vaccines. No serious vaccine-related adverse events have been reported (Markowitz, Dunne et al. 2014). It is contraindicated in people with a history of immediate hypersensitivity to yeast or to any vaccine component. The vaccine should be deferred in patients with moderate or severe acute illnesses. The vaccine is not recommended for use in pregnant women. Lactating women and immune-suppressed female patients can receive the vaccine. The efficacy and the degree of immune response could be poor in the latter (Markowitz, Dunne et al. 2014). HPV vaccination is for primary prevention (serotype-specific with limited cross protection) of carcinoma cervix. There is no risk of getting an HPV infection from the vaccine as the vaccine does not contain live virus. HPV vaccination and regular cervical screening is the most effective way to prevent cervical cancer (Kaarthigeyan 2012).