The day of 8 March constitutes an important opportunity for women to celebrate progress in terms of equality and human rights, the right to health primarily. The anniversary is also a fundamental moment to reflect on how much is still to be done. In fact, "gender discrimination and unequal access to information, prevention and treatment, especially in the poorest countries", Continue to be the main cause of the disadvantage with regard to the state of health and mortality recorded among women, as highlighted by theWorld Health Organization. The situation is perhaps represented in an emblematic way by a specific female pathology: cervical cancer or cervix. According to what reported byWHO, if cervical cancer was the leading cause of death among women 50 years ago, it is currently the fourth leading cause of death by cancer. In particular, about 90% of deaths happen today in developing countries, while the figures are falling exponentially in the "rich" countries, in some of which, like Australia, it is even possible to think about the complete eradication of this tumor in the near future. 

To learn more about the pathology, and fully understand the enormous steps taken by medicine in this area and what tools are available to prevent or control it, the Journal of Italian Healthcare World has interviewed Dr. Alessandra Pipan, specializing in obstetrics and gynecology, who currently practices in Dubai. 

Dr. Alessandra Pipan

Dr. Pipan, can you explain to the Journal readers what cervical cancer consists of?

The cervix is the part of the uterus that faces the vagina. It is covered with a special fabric, very susceptible to the action of external and internal factors that are called risk factors. The tumor begins when some cells of this tissue begin to grow and multiply disorderly and without apparent control. It is thought that the transformation takes place in stages and over a period of years; therefore the incidence of cancer is statistically between 40 and 50 years.

You spoke about great susceptibility to risk factors: which are the main ones? 

Infection with HPV (Human papilloma virus) is considered the most important risk factor for cervical cancer. Causality has been demonstrated for a subset of high-risk strains considered to be oncogenes. In particular, strains 16/18 are considered globally responsible for 70% in cervical carcinomas. Going into more detail, the data of a recent revision of the Tumor Registry in America confirmed the presence of HPV DNA in 90.6 % of cervical carcinomas, 91.1% of anal carcinomas, 75% of vaginal carcinomas, 70% of oropharyngeal carcinomas, in 68.8. % of vulvar carcinomas, 63% of penile carcinomas, 32% of oral cavity carcinomas, 20% of laryngeal tumors and 98.8 % of cervical carcinomas in situ. Other risk factors are: smoking, immune deficiency, prolonged use of oral contraceptives, infection with chlamydia, in utero exposure to DES (diethylstilbestrol). Cancer linked to infection with 16/18 strains is more frequent in young women, while HPV negative neoplasms are more frequent in older women.

So, according to the data you mentioned, the oncogenic effect of HPV infection affects both sexes?

Yes: papilloma virus significantly affects different types of cancer not only female and not only related to the genital apparatus. Furthermore, although genital cancer is very rare in men, over 80% of the male partners of women with HPV infection are 'healthy' carriers.  

What are the symptoms that should never be underestimated that should prompt a woman to consult the gynecologist immediately? 

Unfortunately, the neoplasia itself and the ‘precancerous’ lesions are mostly asymptomatic: abnormal bleeding, spontaneous or after contact, pelvic pain or dyspareunia and in a few advanced forms "foul vaginal discharge".

It is therefore fundamental to carry out regular checks: what frequency do screening recommend, from what age and until what age?

The ASCCP guidelines they recommend it screening from the age of 21. In some countries it is started at the age of 25. Many programs of screening they are traditionally offered with the only one PAP smear to be repeated every three years. Second (ASCO) it would be preferable to carry out the co-testing, or the HPV test carried out concurrently with the Pap-test. It should be performed every five years in women aged 25 to 65, then discontinued except in special cases of women with a history of abnormal results or who are immunosuppressed: in this case the screening it can be extended up to 70 years of age. In clinical practice, the decision regarding which tests to perform and how often it is actually individualized on the basis of the patient's clinical history, geographical area, collateral risk factors, the possibility of performing appropriate follow up

Let's deepen the topic screening: what are the differences between the two type of test PAP smear e HPV test?

The PAP smear it is traditionally considered the test of screening par excellence: a recent review indicates a sensitivity between 50 and 94%. As mentioned above, the possibility of implementing screening based on HPV test, alone or in combination with traditional cytology (co-testing), because it has recently been shown that it has better accuracy. In fact, if 1000 women are screened, 20 will have precancerous lesions: of these 20, the HPV test is able to identify 18, the PAP smear 15. In other words, the women who will develop the tumor incorrectly identified by the type of test performed will be 2 for the HPV test and 5 for the PAP smear

What do the two tests consist of?

The PAP smear it can be collected in the traditional way (with spatula) or on a thin layer (liquid cytology). The latter method offers greater accuracy of interpretation, for example in cases with bleeding, and allows the simultaneous search for HPV DNA. The HPV test it consists in the search for the Viral DNA in a sample of cervical and vaginal cells. The levy can be contextual to the PAP smear. The HPV family consists of about 150 strains, divided between low risk (responsible for common condyloma) and high risk, potential causes of neoplasia. In case of abnormal Pap test and / or presence of high risk HPV, we proceed with investigations aimed at localizing the lesion and determining its severity. These investigations are colposcopy e biopsy. These are outpatient procedures considered second level, also used in place of screening in so-called low resources setting, ie in contexts where other diagnostics are absent.

Can you mention the diagnostic techniques available to men?

For men, the collection of superficial genital cells has not yet proved adequate. The only validated diagnostic consists of the examination of the genitals with ac. acetic and magnification (the equivalent of colposcopy). Other methods such as the detection of antibodies in the blood, which has a sensitivity of only 50%, are not used in clinical diagnostics as well as the search for HPV in urine, or the self sampling

Especially in recent times we hear a lot about the HPV vaccine. Can you explain to the readers of The Journal what it consists of, to whom it is addressed and how effective it is?

THE vaccines available today, depending on the country of residence, they are CervarixGardasil 4 e Gardasil 9. Cervarix is a bivalent vaccine related to the two high-risk HPV strains 16-18. Gardasil 4 is a quadrivalent vaccine related to the two low-risk 6-11 strains and the two high-risk strains 16-18. It is recommended in boys of both sexes aged 11-12 years, but can be given even after 9 years. Vaccination can be extended up to 26 years of age in women and 21 in men (up to 26 in men at high risk). Two doses are considered sufficient in the younger population, otherwise it is administered in three doses. Gardasil 9 extends coverage to five additional strains: 31-33-45-52-58. According to the most recent indications, the administration of Gardasil 9 is extended up to 45 years. It is believed that this vaccine prevent 90% of cervico-carcinomas, with an efficacy of 88% in generally preventing infections from strains present in the vaccine. The longest study of follow up post vaccination lasted almost 10 years and demonstrated the persistence of excellent vaccination coverage. Vaccination is not a treatment, so it cannot change the course of infection, if already present - it can on the other hand be administered even if the infection has been contracted. They are still being studied, on animal models for now, possible therapeutic vaccines.

Does or will the vaccine replace the periodic screening performed by the gynecologist?

Vaccination does not offer protection (cross protection) against the other oncogenic strains: therefore the screening periodic continues to be necessary. It is obviously also important to persist in disseminating an adequate level of correct information regarding other sexually transmitted diseases.

Dr. Pipan, thank you. You were very clear. One last question: what are the main obstacles to the definitive defeat of this disease?

The economic aspect is preponderant, since vaccination campaigns, training, equipment and education for prevention require a lot of money. It is no coincidence that the neoplasia remains widespread in countries where the health and information network is insufficient.  

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