**2. Etiology**

The risk factors for pre malignant tumors of larynx are primarily similar to those of laryngeal carcinoma. These risk factors may cause conversion of a dysplastic lesion into metaplasia and eventually may lead to malignancy but the laryngeal

#### *Premalignant Conditions of Larynx DOI: http://dx.doi.org/10.5772/intechopen.97870*

neoplasia is a preventable disease in the vast majority of cases, which points out the role of various environmental and social factors. The most commonly and strongly implicated factor remains smoking. Burning cigarettes release tar that contains polycyclic aromatic hydrocarbons which have been proven to be carcinogenic and act by damaging the nucleic acids in the cells. Similarly, alcohol consumption may be an independent risk factor & in such people, supraglottic carcinoma is frequently seen. Though alcohol is directly implicated in carcinogenesis, it may be associated with other co morbidities and deficiencies as in malnutrition or vitamin deficiencies. When alcohol consumption is combined with smoking, the risk of neoplasia multiplies.

Other known etiological factor for oropharyngeal carcinoma includes the Human Papilloma Virus or the HPV; the serotypes strongly associated with oropharyngeal carcinoma are 16 and 18 (as seen in carcinoma cervix) [8].

In most HPV positive laryngeal carcinomas, serotype 16 is frequently isolated, while in recurrent respiratory papillomatosis, serotypes 6 and 11 are commonly isolated.

Recurrent respiratory papillomatosis does not usually turn into squamous carcinoma, owing to different pathogenesis, however this transformation may be seen in patients who have a history of exposure to radiation.

The epidemiological studies have shown that the prevalence of HPV in patients of laryngeal carcinoma varies greatly i.e., between 0% to 58% (grossly around 25%), depending upon the investigations and the population [9]. Lately, studies have shown that HPV and carcinoma larynx are not strongly co related. On the other hand, it has been seen that HPV can be present in people with otherwise histologically normal epithelium of larynx and with no signs or symptoms [10].

The association of GERD (Gastro Esophageal Reflux Disorder) with laryngeal malignancy has been explored by many researchers. Olson in 1983 was the pioneer to study the role of chronic laryngopharyngeal reflux (LPR) in laryngeal carcinoma [11]. He found a significant relationship between these two pathologies, where the incidence of laryngeal carcinoma was higher in patients suffering from LPR [7]. On the contrary Chen et al. found no association between GERD and laryngeal neoplasia [12].

Many other environmental factors have been known to increase the risk of laryngeal malignancy such as industrial pollutants like asbestos, malnutrition, lower socioeconomic status etc. [13]. Exposure to radiation for managing other neck tumors like thyroid cancer can also predispose to laryngeal malignancies [14].

Even the role of genetic factors have been implicated to increase the susceptibility of an individual to develop laryngeal neoplasia such as enzymatic polymorphisms in elimination and detoxification of alcohol and smoke produced carcinogens [15].

## **3. Molecular genetics**

The concept of field cancerization was introduced by Slaughter et al in a study of oral cancer [16]. He found that there occurred histopathological abnormalities in the epithelium surrounding the invasive cancer and the abnormalities ranged from keratosis, dysplasia and hyperkeratosis, epithelial hyperplasia etc. With this concept many researchers tried to study the genetics around the tumor site and premalignant conditions to predict their clinical outcome. In many tumor types, including HNSCC (Head and Neck squamous cell carcinoma), p53 inactivation apparently occurs in the transition from the preinvasive to the invasive state [17]. A second

17p13 locus may be altered earlier in progression. Existence of an alternate gene in this region has been implied in the genetic progression of brain and breast cancer [18, 19]. In a study by Califano et al the analysis of premalignant lesions was carried out a genetic level, they concluded that early genetic study of a premalignant lesion could aid and influence our treatment strategies from a conservative to a more aggressive one according to the genetic events detected [20].
