# ESCC as a thorny cancer
### ESCC hotspots in the world
Esophageal cancer has two main histological types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). ESCC accounts for about 85% of cases worldwide and remains the predominant type in most high-incidence populations ([Murphy et al., 2017](#ref-Murphy2017)). ESCC hotspots cluster along
- the **"Asian esophageal cancer belt"** from China westward through Central Asia to northeastern Iran, broadly along the ancient Silk Road ([Craddock, 1993](#ref-Craddock1993); [Jabbari et al., 2008](#ref-Jabbari2008); [Lian et al., 2019b](#ref-Lian2019b));
- the **"East African ESCC corridor"** across Sub-Saharan Africa from the Eastern Cape of South Africa to Sudan; and
- the **southeastern South America** (southern Brazil, Uruguay and northeastern Argentina) ([McCormack et al., 2017](#ref-McCormack2017); [Murphy et al., 2017](#ref-Murphy2017)) (see **Figure 1** ).
**Figure 1.** Geographical distribution of ESCC incidence globally. (Age standardized rate for males according to GLOBOCAN 2012, map modified after [Abnet et al., 2018](#ref-Abnet2018)).
### ESCC as a 'thorny cancer'?
Non-mutagenic tumor-promoting agents, environmental ones in particular, may play a more important role in ESCC etiology than previously thought ([Balmain, 2020](#ref-Balmain2020); [Moody et al., 2021](#ref-Moody2021)). Among the candidate environmental factors are **sharp spicules of biogenic silica** contaminating food, potentially scarifying a narrowed gullet and resulting in chronic irritation of the esophageal mucosa ([Lian et al., 2019a](#ref-Lian2019a); [O'Neill et al., 1986](#ref-ONeill1986), [1982](#ref-ONeill1982); [O'Neill et al., 1980](#ref-ONeill1980); [Rose, 1968](#ref-Rose1968)).
<!-- Map shows the country-level incidence rates; the ESCC hotspots with extremely high incidence cluster in northern China, eastern inland China, southeastern coastal China, East Africa and east coast of South America. -->
### Glass roots of ESCC in China?
This research team led by Tian LW have been pursuing this hypothesis of biogenic glass needles entering diet and contributing to the extremely high incidence of ESCC in northern China ([Deng et al., 2025b](#ref-Deng2025a), [2025a](#ref-Deng2025b); [Lian et al., 2019a](#ref-Lian2019a), [2019b](#ref-Lian2019b)) (**Figure 2**). The glass needles are siliceous hairs on wheat bracts, which easily contaminate wheat flour by evading the winnowing stage due to their high density, and slipping through flour sieves due to their small diameters. In southern China where wheat is consumed less, the glass needles are diatom frustules (cell walls as 'glass boxes') in the guts of trash fish (small edible fish) which are often consumed whole ([Wu et al., 2026](#ref-Wu2026)).
**Figure 2.** Glass roots of ESCC in China? (A) Map of China shows EC mortality rates of females, in 1973-75 (The National Cancer Control Office of the Ministry of Health and Nanjing Institute of Geography of Academia Sinica, 1980). No updated maps are available due to the absence of census data, but the geographic patterns disclosed in these early maps have not changed substantially in the past decades. The geographic patterns are similar between females and males (not shown), indicating some environmental causes in the high-risk areas. (B-G) Acicular, imperceptible micron-level silica fragments may contaminate daily foods from EC endemic areas of North China, North Jiangsu and East Guangdong.
<!-- These glass needles are siliceous hairs on the bract of wheat grown in semi-arid North China, and acicular diatom frustules in water bodies and then in trash fish (mainly filter-feeding fish and other low-trophic level little fish) of North Jiangsu and East Guangdong. These silica needles contaminate wheat flour in North China, river and lake trash fish (for directly making food) in northern Jiangsu and sea trash fish (for making fish sauce, fish rice and dried fish) in eastern Guangdong, then might do microneedling for human esophagus in every meal, and promote carcinogenesis by chronic inflammation. -->
### Glass roots of ESCC in Tanzania?
Lately we are extending this work from China to the world, prompted by an unexpected and alarming finding in Tanzania (**Figure 3**). The dried trash fish contained extremely high concentrations of frustules with needle-shaped ones overwhelmingly dominant.
**Figure 3.** Needle-shaped diatom frustules from water to a dining table in Tanzania. (A) Fishermen catch trash fish by a wooden canoe. (B) The trash fish catch is unloaded on the courtyard. (C) Trash fish are boiled over firewood. (D) Boiled trash fish are dried and sold at the local market. (E,F) Electron micrographs showing abundant needle-shaped diatom frustules after acid removal of organic matter from the trash fish.
Tanzania has one of the highest ESCC incidence rates in the world. It is not alone: five countries along the East African Rift Valley, namely, Tanzania, Kenya, Malawi, Uganda, and Ethiopia, rank among the top ten globally in age-standardized ESCC incidence ([Ferlay et al., 2024](#ref-GCO2024)). The convergence of extreme dietary exposure to biogenic silica needles and extreme ESCC burden within the same geographic corridor demands systematic investigation.
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