Table 1  Pathogenetically based clinicopathological characteristics of vulvar squamous cell carcinoma 2 ,  4 ,  5 ,  6 ,  10 ,  11 ,  20 ,  42 .

	HPV-associated	HPV-independent	Uncertain
	p16 + /p53 −	p16 − /p53 +	p16 − /p53 −
Frequency	40%	50 – 60%	20%
Age	40 – 60 years of age	50 – 70 years of age	60 – 70 years of age
Precancerous lesion	VIN 2/3 (H-SIL)	HPV-independent VIN (d-VIN,? VAAD,? DEVIL)	? (d-VIN-/VAAD-like?)
Etiopathogenesis	High-risk HPV infection	p53 alteration	? (NOTCH-1/HRAS/ PIK3CA mutation?)
Biomarker expression	p16 positive (block staining)	p53-aberrant staining pattern	p16 negative/p53 wt
Histology (Heller et al. 2020)	Non-keratinizing (ca. 66%)	Keratinizing (80 – 90%)	Keratinizing/ non-keratinizing
Inguinal lymph node metastases	30%	40%	30%
Radio(chemo)sensitivity	Usually sensitive	Less sensitive	Possibly less sensitive
Prognosis	Better	Poorer	Intermediate
Local recurrence (Nooij et al. 2017) 10	5.3%	22.6%	16.3%
2-year DFS (Woelber et al. 2021) 11	64%	47%	60%
5-year DSS (Barlow et al. 2020) 5	89%	75%	83%
Overall survival (Woelber et al. 2021) 11	82%	70%	75%