uterine cervical cancer in the population of Nosy Be, Madagascar

Pathologist at the microscope and local staff reviewing the cytological reports

In a previous post I described the results of a medical mission we made in september 2010 to promote secondary prevention of uterine cervical cancer by pap smear cytological screening in women living in Nosy Be Island, Madagascar. The mission was repeated in April 2011 and took place at the Dispensaire of the Organisation Medicale Interenterpresises of Nosy Be (OMINO) in Hellville. The data we collected confirm our previous results that in the population of Nosy Be the incidence of uterine cervical carcinoma and its precursor lesions is significantly high. 
So far, we have examined cumulatively 278 women aged 16 to 57. In both missions we managed to perform pap smear evaluation with immediate reporting and immediate colposcopy and biopsy on a same-day basis. To summarize, pap smear sampling started early in the morning and was performed by two physicians, then slides were immediately stained and interpreted by a Pathologist who was able to release a cytopathological report at the end of the morning. Then, women bearing abnormalities in their pap smear were invited to undergo immediate colposcopy which was performed in the  early afternoon. Biopsy samples were then collected and processed for histological evaluation. Histological processing was completed in Italy at the department of Pathology, Fatebenefratelli Hospital, in Milano, Italy. 

women waiting for their turn for pap smear sampling

Immediate cytological reporting allowed for women with pap smear abnormalities to undergo immediate colposcopy thus preventing the risk of patients’ drop out in the screening programme. This is the most rewarding result for our efforts because women in these countries often fail to show up again when they are subsequently (i.e. many days or even months later) invited to undergo further evaluation, and the screening procedure thus fails to confirm cervical lesions by colposcopy and histology. 
Overall, we detected 5 women with high grade lesions according to the Bethesda System, 2001, and three of them were diagnosed as having squamous cell carcinoma in situ on biopsy examination.  Low grade lesions were found in other 25 women who are going to be re-evaluated within 6 months after the first pap smear. The overall cumulative incidence of pap smear abnormalities in this population is 10.79%, and this value is higher than the World Health Organization’s estimates of 10% (see "Comprehensive Cervical Cancer Control. A guide to essential practice", p. 40, World Health Organization, 2006) for the previously unscreened population in Madagascar. The above value is about 5-fold to 8-fold higher than the incidence of abnormalities in the screened population living in countries of the high-income developed world.

In un precedente post ho parlato della missione medica da noi eseguita in settembre del 2010 e finalizzata a promuovere la prevenzione del carcinoma della cervice uterina nella popolazione residente di Nosy Be, in Madagascar. Tale missione è stata ripetuta in Aprile 2011 e ha avuto luogo presso il Dispensario della Organisation Medicale Interenterprises di Nosy Be (OMINO) a Hellville, il capoluogo dell'isola. I dati raccolti confermano la nostra precedente impressione che l’incidenza di questa neoplasia in quell’area geografica è decisamente elevata. Abbiamo esaminato in tutto 278 donne e identificato 5 casi con lesioni ad "alto rischio" di cui 3 con carcinoma. Sono state identificate inoltre 25 donne portatrici di lesioni a “basso rischio” che verranno sottoposte a controllo ravvicinato. In entrambe le missioni abbiamo provveduto a eseguire la lettura immediata del pap test allo scopo di poter sottoporre le pazienti che necessitavano di colposcopia e biopsia nello stesso giorno. Questa modalità operativa ha consentito di annullare la quota di casi che solitamente non si ripresenta al controllo quando le pazienti vengono riconvocate a distanza di tempo dal pap test e ciò ha ottimizzato gli effetti dello screening. L’incidenza di lesioni riscontrate, pari al 10,79%, appare decisamente elevata se si pensa che l’Organizzazione Mondiale della Sanità stima un’incidenza massima del 10% per la popolazione del Madagascar. L’incidenza è da 5 a 8 volte superiore a quella riscontrata nella popolazione femminile sottoposta a regolare screening nei paesi occidentali.

Metronomic chemotherapy to treat cancer in low-resources countries

Treatment of many types of cancer is based on the use of chemotherapy. According to this approach, some special drugs, the chemotherapeutic agents, are administered in high doses which are lethal for cancer cells with the aim of eradicating them from the body. High dosage causes, however, severe side effects and drug resistance, thus chemotherapy has often to be stopped and/or becomes useless. As an alternative to conventional chemotherapy metronomic chemotherapy is gaining a great interest in the current scenario of oncological therapy. The theory behind “metronomic” chemotherapy is to administer very low doses of conventional anti-cancer drugs to attack vascular cells that supply oxygen and nourishment to the tumor (socalled “antiangiogenic” effect). The dosages are too low to kill the cancer cells directly, but high enough to arrest the growth of vessels that supply nutrients to the cancer cells. In other words, giving the drug in very low doses, and for a prolonged period of time (“metronomic” administration), such a therapy can prevent the formation of new capillaries, keeping the cancer from growing. Several studies have established the efficacy of metronomic chemotherapy in the treatment of a variety of cancer types. The efficacy seems not only to be based upon anti-angiogenic effect but also on the restoration of anticancer immune response and induction of tumor dormancy, as recently discussed by Pasquier et al. in an article which appeared in Nature Review Clinical Oncology. The chance of obtaining a successful treatment while minimizing side effects and drug resistance also means that chemotherapeutic agents can be administered in small cancer centers with minimal supportive care and this is of paramount importance to provide effective cancer treatment in the low-income and low-resources developing countries.  In fact, in many types of childhood and adult cancers, metronomic treatment protocols prove to be effective even if used on a totally outpatient basis and, most importantly, with no significant side effect. Thus the metronomic approach  represents a promising, innovative, simple, and affordable tool to treat cancer patients in the low-resources settings of the world. Metronomic protocols are now being implemented to treat leukemia and malignant lymphomas, but also cancer of the breast, ovary and the gastrointestinal tract.

HPV vaccination in male to prevent uterine cervical cancer

The origin of cancer of the cervix uteri is directly linked to a chronic infection of selected (so called “high risk”) types of human papilloma virus (HPV).  The virus is readily transmitted from men to women by the sexual intercourse and greatly affects the risk of disease in women. It is for this reason that understanding the nature of HPV in men is of crucial public health importance and can be used in modeling to establish whether vaccinating men against HPV would be cost effective. An Article published by Professor Anna R Giuliano and colleagues, of the H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA, in the prestigous medical journal the Lancet  shows that approximately 50% of men from a sample of the general population are infected with the virus. The study analysed 1159 men aged 18 to 70 years (mean 32 years) from the USA, Brazil, and Mexico, all of whom were HIV negative and had no history of cancer. They were assessed every six months for an average of more than two years. The incidence of a new genital HPV infection with any HPV type was 38.4 per 1000 person months. The chances of cancer-causing (oncogenic) HPV infection was 2.4 times higher from men who had had many female partners compared with no partners or just one partner. The authors say: 'We noted no association with age and incidence of any, oncogenic, or non-oncogenic HPV types, although the probability of clearing these infections increased with age." They conclude: "The incidence of genital HPV infection in men was high and relatively constant across age groups in Brazil, Mexico, and the USA. The results from this study provide much needed data about the incidence and clearance of HPV infection in men; these data are essential for the development of realistic cost-effectiveness models for male HPV vaccination internationally". HPV vaccination of men will protect not only them but will also have great implications for their sexual partner. Vaccination of both females and males could represent the best way to fight uterine cervical cancer.