Table 4.
Summary of cohort and case-control studies on all known and putative risk factors for vulvar cancer published between 1980 and 2020. Part 3.
| Risk Factor | First Author * [Ref.] | Year | Country | Design | Representativeness | Exposed | Cases | Controls | Age † |
|---|---|---|---|---|---|---|---|---|---|
| Induced abortion | Sherman [79] | 1994 | US | CC | 3-county, cancer-registry-based case series | NA | 81 | 1010 | Mean, 59 |
| Miscarriage | Sherman [79] | 1994 | US | CC | 3-county, cancer-registry-based case series | NA | 81 | 1010 | Mean, 59 |
| Prior tubal ligation | Coffey [33] | 2016 | UK | C | Cohort of attenders to a population-based MSP | 1,300,042 | 878 | NA | Range, 49–65 |
| Prior hysterectomy | Coffey [33] | 2016 | UK | C | Cohort of attenders to a population-based MSP | 1,300,042 | 718 | NA | Range, 49–65 |
| Prior hysterectomy | Brinton [30] | 2017 | US | CC | 8-state/area cohort of registered retired persons | 201,469 | 170 | NA | Mean, 61 |
| OC use | Sherman [79] | 1994 | US | CC | 3-county, cancer-registry-based case series | NA | 81 | 1010 | Mean, 59 |
| OC use | Coffey [33] | 2016 | UK | C | Cohort of attenders to a population-based MSP | 1,300,042 | 884 | NA | Range, 49–65 |
| OC use | Brinton [30] | 2017 | US | CC | 8-state/area cohort of registered retired persons | 201,469 | 170 | NA | Mean, 61 |
| Oestrogen use | Sherman [79] | 1994 | US | CC | 3-county, cancer-registry-based case series | NA | 81 | 1010 | Mean, 59 |
| Menopausal hormone use | Coffey [33] | 2016 | UK | C | Cohort of attenders to a population-based MSP | 917,711 | 653 | NA | Range, 49–65 |
| Menopausal hormone use | Brinton [30] | 2017 | US | CC | 8-state/area cohort of registered retired persons | 201,469 | 170 | NA | Mean, 61 |
| Metabolic syndrome | Nagel [64] | 2011 | Germany | C | 3-country cohort from primary prevention programmes | 288,834 | 82 | NA | Mean, 44 |
| Blood glucose | Nagel [64] | 2011 | Germany | C | 3-country cohort from primary prevention programmes | 288,834 | 82 | NA | Mean, 44 |
| Triglyceride concentration | Nagel [64] | 2011 | Germany | C | 3-country cohort from primary prevention programmes | 288,834 | 82 | NA | Mean, 44 |
| Cholesterol concentration | Nagel [64] | 2011 | Germany | C | 3-country cohort from primary prevention programmes | 288,834 | 82 | NA | Mean, 44 |
| Diabetes | Coffey [33] | 2016 | UK | C | Cohort of attenders to a population-based MSP | 1,300,042 | 897 | NA | Range, 49–65 |
| Diabetes | Brinton [30] | 2017 | US | CC | 8-state/area cohort of registered retired persons | 201,469 | 170 | NA | Mean, 61 |
| BMI | Sherman [79] | 1994 | US | CC | 3-county, cancer-registry-based case series | NA | 81 | 1010 | Mean, 59 |
| BMI | Parazzini [68] | 1995 | Italy | CC | Hospital-based case series | NA | 125 | 541 | Median, 63 |
| BMI | Parazzini [68] | 1995 | Italy | CC | Hospital-based case series | NA | 125 | 541 | Median, 63 |
| BMI | Parazzini [68] | 1995 | Italy | CC | Hospital-based case series | NA | 125 | 541 | Median, 63 |
| BMI | Nagel [64] | 2011 | Germany | C | 3-country cohort from primary prevention programmes | 288,834 | 82 | NA | Mean, 44 |
| BMI | Coffey [33] | 2016 | UK | C | Cohort of attenders to a population-based MSP | 1,300,042 | 638 | NA | Range, 49–65 |
| BMI | Coffey [33] | 2016 | UK | C | Cohort of attenders to a population-based MSP | 1,300,042 | 545 | NA | Range, 49–65 |
| BMI | Brinton [30] | 2017 | US | CC | 8-state/area cohort of registered retired persons | 201,469 | 170 | NA | Mean, 61 |
| Coffee consumption | Mabuchi [58] | 1985 | US | CC | Multicentre hospital-based case series | NA | 149 | 149 | 81% ≥50 |
| Coffee consumption | Mabuchi [58] | 1985 | US | CC | Multicentre hospital-based case series | NA | 149 | 149 | 81% ≥50 |
| Coffee consumption | Parazzini [68] | 1995 | Italy | CC | Hospital-based case series | NA | 125 | 541 | Median, 63 |
| Meat consumption | Parazzini [68] | 1995 | Italy | CC | Hospital-based case series | NA | 125 | 541 | Median, 63 |
| Meat consumption | Parazzini [68] | 1995 | Italy | CC | Hospital-based case series | NA | 125 | 541 | Median, 63 |
| Green vegetable consumption | Parazzini [68] | 1995 | Italy | CC | Hospital-based case series | NA | 125 | 541 | Median, 63 |
| Green vegetable consumption | Parazzini [68] | 1995 | Italy | CC | Hospital-based case series | NA | 125 | 541 | Median, 63 |
| Carrot consumption | Parazzini [68] | 1995 | Italy | CC | Hospital-based case series | NA | 125 | 541 | Median, 63 |
| Carrot consumption | Parazzini [68] | 1995 | Italy | CC | Hospital-based case series | NA | 125 | 541 | Median, 63 |
| Alcohol consumption | Parazzini [68] | 1995 | Italy | CC | Hospital-based case series | NA | 125 | 541 | Median, 63 |
| Alcohol consumption | Weiderpass [87] | 2001 | Sweden | C | Nationwide, population-based cohort | 36,856 | 8 | NA | Mean, 42 |
| Alcohol consumption | Madsen [61] | 2008 | Denmark | CC | Nationwide, cancer-registry-based series | NA | 116 | 518 | Median, 63 |
| Alcohol consumption | Coffey [33] | 2016 | UK | C | Cohort of attenders to a population-based MSP | 1,300,042 | 890 | NA | Range, 49–65 |
| Alcohol consumption | Brinton [30] | 2017 | US | CC | 8-state/area cohort of registered retired persons | 201,469 | 170 | NA | Mean, 61 |
| Risk factor | [Ref.] | Comparison | Disease | Measure | Result (95% CI) | Adjustment variables | |||
| Induced abortion | [79] | Exposure vs. no exposure | VSCC | OR | 1.9 (1.0–3.8) | Age, EDU, smoking, no. of sexual partners, genital warts | |||
| Miscarriage | [79] | Exposure vs. no exposure | VSCC | OR | 0.9 (0.5–1.7) | Age, EDU, smoking, no. of sexual partners, genital warts | |||
| Prior tubal ligation | [33] | Exposure vs. no exposure | VC | RR | 0.91 (0.77–1.07) | Age, DEPRI, smoking, alcohol, BMI, D, age at M, parity, OC, HYST, CIN3 | |||
| Prior hysterectomy | [33] | HYST + oophorect. vs. no HYST | VC | RR | 1.08 (0.83–1.39) | Age, DEPRI, smoking, alcohol, BMI, D, age at M, parity, OC, CIN3 | |||
| Prior hysterectomy | [30] | Exposure vs. no exposure | VC | HR | 1.30 (0.92–1.83) | Age, race, smoking, BMI, marital status, OC, menopausal hormone | |||
| OC use | [79] | ≥5 years vs. never | VSCC | OR | 0.4 (0.2–1.3) | Age, EDU, smoking, no. of sexual partners, genital warts | |||
| OC use | [33] | Ever vs. never | VC | RR | 1.08 (0.94–1.24) | Age, DEPRI, smoking, alcohol, BMI, D, age at M, parity, HYST, CIN3 | |||
| OC use | [30] | ≥10 years vs. <1 | VC | HR | 0.75 (0.39–1.45) | Age, race, smoking, BMI, marital status, menopausal hormone | |||
| Oestrogen use | [79] | Ever vs. never | VSCC | OR | 1.2 (0.6–2.3) | Age, EDU, smoking, no. of sexual partners, genital warts | |||
| Menopausal hormone use | [33] | Current vs. never | VC | RR | 0.86 (0.73–1.02) | Age, DEPRI, smoking, alcohol, BMI, D, age at M, parity, OC, HYST, CIN3 | |||
| Menopausal hormone use | [30] | Current, ≥10 years vs. never | VC | HR | 0.88 (0.58–1.36) | Age, race, smoking, BMI, marital status, OC | |||
| Metabolic syndrome | [64] | For 1 SD INC in the stand. z-score | VC | HR | 1.78 (1.30–2.41) | Age, smoking | |||
| Blood glucose | [64] | For 1 SD INC in the stand. z-score | VC | HR | 1.98 (1.10–3.58) | Age, smoking | |||
| Triglyceride concentration | [64] | For 1 SD INC in the stand. z-score | VC | HR | 2.09 (1.39–3.15) | Age, smoking | |||
| Cholesterol concentration | [64] | For 1 SD INC in the stand. z-score | VC | HR | 1.08 (0.77–1.49) | Age, smoking | |||
| Diabetes | [33] | Exposure vs. no exposure | VC | RR | 0.87 (0.58–1.30) | Age, DEPRI, smoking, alcohol, BMI, age at M, parity, OC, HYST, CIN3 | |||
| Diabetes | [30] | Exposure vs. no exposure | VC | HR | 1.05 (0.58–1.93) | Age, race, smoking, BMI, marital status, OC, menopausal hormone | |||
| BMI | [79] | Highest vs. lowest category | VSCC | OR | 2.9 (1.5–5.8) | Age, EDU, smoking, no. of sexual partners, genital warts | |||
| BMI | [68] | 23.5–25.3 vs. <21.3 | VC | OR | 1.8 (0.8–3.6) | Age, EDU | |||
| BMI | [68] | 25.4–28.1 vs. <21.3 | VC | OR | 2.5 (1.2–5.0) | Age, EDU | |||
| BMI | [68] | ≥28.2 vs. 21.3 | VC | OR | 2.5 (1.2–5.2) | Age, EDU | |||
| BMI | [64] | For 1 SD INC in the stand. z-score | VC | HR | 1.36 (1.11–1.69) | Age, smoking | |||
| BMI | [33] | 25.0–29.9 vs. <25.0 | VC | RR | 1.19 (1.02–1.39) | Age, DEPRI, smoking, alcohol, D, age at M, parity, OC, HYST, CIN3 | |||
| BMI | [33] | ≥30.0 vs. <25.0 | VC | RR | 1.71 (1.44–2.04) | Age, DEPRI, smoking, alcohol, D, age at M, parity, OC, HYST, CIN3 | |||
| BMI | [30] | ≥30.0 vs. <25.0 | VC | HR | 1.62 (1.10–2.40) | Age, race, smoking, marital status, OC, menopausal hormone | |||
| Coffee consumption | [58] | 3–4 cups/day vs. <1 | VC | OR | 2.99 (NR, p < 0.05) | NR | |||
| Coffee consumption | [58] | ≥5 cups/day vs. <1 | VC | OR | 2.42 (NR, p < 0.05) | NR | |||
| Coffee consumption | [68] | ≥3 cups/day vs. 0 | VC | OR | 0.8 (0.4–1.3) | Age, EDU, BMI | |||
| Meat consumption | [68] | 4–5 portions/week vs. ≥6 portions | VC | OR | 1.0 (0.5–1.8) | Age, EDU, BMI | |||
| Meat consumption | [68] | <4 portions/week vs. ≥6 | VC | OR | 1.5 (0.9–2.4) | Age, EDU, BMI | |||
| Green vegetable consumption | [68] | 7–13 portions/week vs. ≥14 | VC | OR | 1.1 (0.6–1.8) | Age, EDU, BMI | |||
| Green vegetable consumption | [68] | <7 portions/week vs. ≥14 | VC | OR | 2.0 (1.2–3.4) | Age, EDU, BMI | |||
| Carrot consumption | [68] | 1 portion/week vs. ≥2 | VC | OR | 1.3 (0.7–2.2) | Age, EDU, BMI | |||
| Carrot consumption | [68] | <1 portion/week vs. ≥2 | VC | OR | 1.4 (0.9–2.2) | Age, EDU, BMI | |||
| Alcohol consumption | [68] | Regular vs. never | VC | OR | 1.1 (0.7–1.7) | Age, EDU, BMI | |||
| Alcohol consumption | [87] | Exposed vs. general population | VSCC | SIR | 1.0 (0.4–2.0) | Age, year | |||
| Alcohol consumption | [61] | 0 consumption-years vs. <10 | VSCC | OR | 0.37 (0.20–0.70) | Age, EDU, smoking, marital status, anogenital warts | |||
| Alcohol consumption | [33] | ≥3 units/week vs. 0–2 | VC | RR | 0.87 (0.75–1.00) | Age, DEPRI, smoking, BMI, D, age at M, parity, OC, HYST, CIN3 | |||
| Alcohol consumption | [30] | ≥1.0 vs. 0 | VC | HR | 0.77 (0.44–1.33) | Age, race, smoking, BMI, marital status, OC, menopausal hormone | |||
BMI = body mass index; C = cohort; CC = case-control; CIN = cervical intraepithelial neoplasia; D = diabetes; DEPRI = deprivation; EDU = education; HR = hazard ratio; HYST = hysterectomy; INC = increment; M = menarche; MSP = mammography screening programme; NA = not applicable; NR = not reported; OC = oral contraceptive; oophorect. = oophorectomy; OR = odds ratio; ref. = reference; RR = relative risk; SD = standard deviation; stand. = standardised; UK = United Kingdom; US = United States; VC = vulvar cancer; vs. = versus; VSCC = vulvar squamous cell carcinoma. * In the case of international authorship, the country of the first author is indicated. † The best information made available in the article is indicated. In general, age refers to the age of cases at diagnosis in case-control studies and the age at entry into cohort studies. If possible, age is expressed in completed years.