Table 1 Summary of existing studies on cancer risk in relation to tonsillectomy

Hematopoietic malignancies

 Vestergaard (2010) [8] Denmark

Cohort study

2.1 million person-years in individuals with tonsillectomy; 72 incident cases of HD

Among persons under 15 years of age:

1–4 years after tonsillectomy, RR = 3.9 (95%CI: 1.4–11)

 > 5 years after tonsillectomy, RR = 3.5 (95%CI: 1.4–8.5)

 Liaw (1997) [9] Sweden

Cohort study

55,169 individuals with tonsillectomy; 20 incident cases of HD

 > 1 year after tonsillectomy:

Overall SIR = 1.4 (95%CI: 0.9–2.2)

Age at tonsillectomy < 12: SIR = 4.1 (95%CI: 1.6–8.4)

Age at tonsillectomy 12–19: SIR = 1.3 (95%CI: 0.6–2.5)

Age at tonsillectomy ≥ 20: SIR = 0.7 (95%CI: 0.2–1.8)

 Becker (2005) [10] Germany

Case–control study

710 cases (115 HD, 554 B-NHL, 35 T-NHL, and 6 others) and 710 controls

Overall:

HD: OR = 1.32 (95%CI: 0.80–2.19)

Follicular lymphoma: OR = 1.84 (95%CI: 1.15–2.93)

CLL: OR = 1.42 (95%CI: 0.88–2.29)

B-NHL: OR = 1.24 (95%CI: 0.96–1.61)

T-NHL: OR = 0.86 (95%CI: 0.36–2.06)

MM: OR = 0.78 (95%CI: 0.42–1.43)

Age at tonsillectomy ≤ 6 years:

HD: OR = 2.05 (95%CI: 0.72–5.84)

Follicular lymphoma: OR = 4.93 (95%CI: 1.97–12.3)

CLL: OR = 4.01 (95%CI: 1.43–11.3)

B-NHL: OR = 2.97 (95%CI: 1.57–5.62)

T-NHL: OR = 3.46 (95%CI: 0.69–17.3)

MM: OR = 1.00 (95%CI: 0.13–8.12)

 Vineis (2003) [11] Italy

Case–control study

574 cases (261 LL and 313 ML) and 1718 controls

LL: OR = 0.9 (95%CI: 0.7–1.3)

ML: OR = 0.9 (95%CI: 0.6–1.1)

 Vineis (2000) [12] Italy

Case–control study

2669 cases (1388 NHL, 354 HD, 263 MM, 261 LL, 313 ML, and 90 others) and 1718 controls

NHL: OR = 1.1 (95%CI: 0.9–1.3)

HD: OR = 1.0 (95%CI: 0.7–1.3)

MM: OR = 0.8 (95%CI: 0.6–1.2)

LL: OR = 0.8 (95%CI: 0.6–1.1)

ML: OR = 0.8 (95%CI: 0.6–1.1)

 Schüz (1999) [13] Germany

Case–control study

1010 children with acute leukemia and 1010 controls

OR = 1.4 (95%CI: 1.0–1.9)

 Gledović (1991) [14] Serbia

Case–control study

113 cases with HD, 113 neighborhood controls, and 113 hospital controls

Neighborhood controls: OR = 0.91 (95%CI: 0.45–1.81)

Hospital controls: OR = 0.74 (95%CI: 0.38–1.43)

 Serraino (1991) [15] Italy

Case–control study

152 cases with HD and 613 controls

Any histology type: OR = 0.9 (95%CI: 0.6–1.4)

Nodular sclerosis: OR = 1.1 (95%CI: 0.6–1.9)

 Bonelli (1990) [16] Italy

Case–control study

160 cases with HD and 185 hospital controls

Age at tonsillectomy < 10: RR = 0.46 (95%CI: 0.22–0.94)

Age at tonsillectomy 11–20: RR = 1.10 (95%CI: 0.39–2.82)

Age at tonsillectomy ≥ 21: RR = 1.14 (95%CI: 0.37–3.51)

 Mueller (1987) [17] USA

Case–control studies

684 cases with HD and 786 sibling controls

15–39 years: RR = 1.0 (95%CI: 0.72–1.4)

40–54 years: RR = 1.5 (95%CI: 0.67–3.3)

 ≥ 55 years: RR = 3.0 (95%CI: 1.3–6.9)

 Hardell (1983) [18] Sweden

Case‐control study

59 cases with HD and 117 controls

RR = 2.7 (95%CI: 0.6–11.6)

 Silingardi (1982) [19] Italy

Case–control study

505 cases with HD, 226 cases with NHL, and 731 controls

HD: RR = 0.88 (p: NS)

NHL: RR = 1.23 (p: NS)

 Vianna (1980) [20] USA

Case‐control study

81 cases with HD and 81 sibling controls

RR = 2.7 (95%CI: 1.1–6.5)

 Kirchhoff (1980) [21] Brazil

Case–control study

70 cases with HD and 128 sibling controls

RR = 2.5 (95%CI: 1.0–6.0)

 Henderson (1979) [22] USA

Case–control study

218 cases with HD and 218 controls

RR = 0.98 (p: NS)

 Andersen (1978) [23] Denmark

Case‐control study

63 cases with HD and 182 controls

No association (p = 0.79)

 Abramson (1978) [24] Israel

Case–control study

403 of cases with HD and 403 controls

HD: RR = 1.3 (p: NS)

Mixed cellularity: RR = 8.5 (p < 0.0004)

Nodular sclerosis: RR = 0.7 (p: NS)

 Paffenbarger (1977) [25] USA

Case–control study

45 cases with HD and 180 classmate controls

RR = 0.9 (p: 0.84)

 Vianna (1974) [26] USA

Case–control study

95 cases with HD and 95 sibling controls

RR = 2.0 (95%CI: 1.1–3.6)

 Johnson (1972) [27] USA

Case–control study

174 cases with HD and 472 sibling controls

No association (p: NS)

 Vianna (1971) [28] USA

Case–control study

109 cases with HD and 109 controls

67 of 101 cases vs. 43 of 107 controls with tonsillectomy (p < 0.001)

 Ruuskanen (1971) [29] Finland

Case–control study

53 cases with HD and 53 controls

5 of 53 cases vs. 7 of 53 controls with tonsillectomy (p: NS)

 Freeman (1971) [30] USA

Case–control study

310 children with acute leukemia and 855 controls

No association (p: NS)

Solid tumors

 Chaturvedi (2016) [31] Sweden

Cohort study

225,718 individuals with tonsillectomy; 144 incident cases of head and neck cancer

> 1 year after tonsillectomy:

Tonsil: SIR = 0.31 (95%CI: 0.08–0.79)

Non-tonsil oropharyngeal: SIR = 1.61 (95%CI: 0.77–2.95)

Base of tongue: SIR = 1.63 (95%CI: 0.66–3.36)

Other head and neck: SIR = 0.92 (95%CI: 0.64–1.27)

> 5 years after tonsillectomy:

Tonsil: SIR = 0.17 (95%CI: 0.02–0.62)

Base of tongue: SIR = 1.31 (95%CI: 0.42–3.05)

 Fakhry (2015) [32] Denmark

Cohort study

90,775 individuals with tonsillectomy; 52 incident cases of oropharyngeal cancer

> 1 year after tonsillectomy:

< 60 years:

Oropharyngeal: RR = 0.6 (95%CI: 0.4–0.9)

Tonsil: RR = 0.2 (95%CI: 0.06–0.4)

Base of tongue: RR = 0.5 (95%CI: 0.2–1.4)

≥ 60 years:

Oropharyngeal: RR = 2.5 (95%CI: 1.7–3.8)

Tonsil: RR = 1.8 (95%CI: 0.9–3.6)

Base of tongue: RR = 4.2 (95%CI: 1.8–9.3)

 Combes (2021) [33] France

Case-case study

363 cases with oropharyngeal cancer and 682 cases with non-oropharyngeal head and neck cancers

Oropharyngeal: OR = 1.1 (95%CI: 0.8–1.4)

Tonsil: OR = 0.4 (95%CI: 0.2–0.8)

Base of tongue: OR = 1.8 (95%CI: 1.1–3.1)

Tonsil and base of tongue: OR = 0.9 (95%CI: 0.6–1.4)

Other oropharyngeal cancer: OR = 1.2 (95%CI: 0.9–1.7)

 Garman (2020) [34] USA

Case–control study

396 cases with esophageal adenocarcinoma and 1102 controls

OR = 1.8 (95%CI: 1.2–2.7)

 Zevallos (2016) [2] USA

Case–control study

361 cases with oropharyngeal cancer and 1378 controls

Oropharyngeal: OR = 0.63 (95%CI: 0.47–0.85)

Base of tongue: OR = 1.95 (95%CI: 1.25–3.06)

HPV-positive base of tongue: OR = 2.46 (95%CI: 1.22–4.95)

Tonsil: OR = 0.22 (95%CI: 0.13–0.36)

HPV-positive tonsil: OR = 0.17 (95%CI: 0.08–0.34)

P16-positive base of tongue: OR = 2.24 (95%CI: 1.16–4.35)

P16-positive tonsil: OR = 0.14 (95%CI: 0.07–0.31)

 Zhang (2014) [35] USA

Case–control study

215 cases with pancreatic cancer and 676 controls

OR = 0.67 (95%CI: 0.48–0.94)

 Brasky (2009) [36] USA

Case–control study

740 cases with breast cancer and 810 controls

Premenopausal: OR = 1.50 (95%CI: 1.08–2.08)

Postmenopausal: OR = 1.05 (95%CI: 0.79–1.38)

 Zivaljevic (2004) [37] Serbia

Case–control study

110 cases with thyroid cancer and 110 hospital controls

OR = 1.11 (95%CI: 0.58–2.11)

 Yasui (2001) [38] USA

Case–control study

537 cases with breast cancer and 492 controls

Age at tonsillectomy 0–4: OR = 0.82 (95%CI: 0.50–1.35)

Age at tonsillectomy 5–9: OR = 1.05 (95%CI: 0.76–1.43)

Age at tonsillectomy 10–14: OR = 1.08 (95%CI: 0.72–1.64)

Age at tonsillectomy ≥ 15: OR = 1.68 (95%CI: 1.09–2.6)

 Ilić (1996) [39] Serbia

Case–control study

101 cases with prostate cancer and 202 controls

7 of 101 cases vs. 10 of 202 controls with tonsillectomy (p: NS)

 Bueno (1992) [40] Netherlands

Case–control study

176 cases with exocrine pancreatic carcinoma and 487 controls

OR = 0.86 (95%CI: 0.55–1.36)

 Whittemore (1985) [41] USA

Case–control study

243 cases with prostate cancer and 972 controls

RR = 1.9 (95%CI: 1.4–2.6)

 Gold (1985) [42] USA

Case–control study

201 cases with pancreatic cancer and 402 controls (201 hospital controls and 201 non-hospital controls)

Hospital controls: OR = 0.29 (95%CI: 0.14–0.59)

Non-hospital controls: OR = 0.26 (95%CI: 0.12–0.59)

 Lubin (1982) [43] Canada

Case–control study

577 cases with breast cancer and 826 controls

> 65 years: RR = 2.3 (95%CI: 1.3–3.9)

Any cancer

 Sun (2015) [44] Taiwan

Cohort study

997 individuals with tonsillectomy, 37 incident cases of cancer

> 3 years after tonsillectomy: IRR = 1.57 (95%CI: 1.02–2.41)

 Cassimos (1973) [45] Greece

Case–control study

500 patients with cancer and 500 controls

11 of 500 cases vs. 45 of 500 controls with tonsillectomy (p < 0.01)

 Gross (1966) [46] USA

Case–control study

300 cases with cancer and 200 controls with noncancerous diseases

23% of cases vs. 24% of controls with tonsillectomy (p: NS)

 Howie (1996) [47] Scotland

Case–control study

1019 cases with cancer and 623 controls

23% of cases vs. 12% of controls with tonsillectomy (p < 0.05)

 Kessler (1969) [48] USA

Case–control study

461 cases with cancer and 223 controls

Overall: RR = 1.17 (p: NS)

Male: RR = 1.26 (p: NS)

Female: RR = 1.06 (p: NS)

Cancer site:

Buccal cavity (male): RR = 1.71 (p: NS)

Colon and rectum (Male): RR = 1.87 (p: NS)

Respiratory (male): RR = 1.43 (p: NS)

Breast (female): RR = 1.07 (p: NS)

Genitalia (female): RR = 0.79 (p: NS)