Vulva, vagina & female urethra

Squamous carcinoma and precursor lesions

HPV associated squamous cell carcinoma

Last author update: 1 April 2015
Last staff update: 15 March 2022

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PubMed Search: Squamous cell carcinoma [title] vulva "loattrfree full text"[sb]

Priya Nagarajan, M.D., Ph.D.
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Cite this page: Nagarajan P. HPV associated squamous cell carcinoma. website. Accessed September 26th, 2023.
Definition / general
  • Includes malignancies originating from keratinizing and nonkeratinizing squamous epithelia of vulva
  • Comprise 90 - 95% of the estimated 5,150 cancers of vulva in 2015 (CA Cancer J Clin 2015;65:5)
  • Overall 5 year survival rate is ~70% (~90% in node negative patients) (Int J Gynaecol Obstet 2014;125:97)
  • Labia majora are most common site but tumors that involve clitoris require extensive surgery
  • Two distinct pathways: (J Skin Cancer 2011;2011:951250, J Low Genit Tract Dis 2013;17:267)
  • Human papillomavirus (HPV) dependent:
    • 20 - 40% of vulvar SCCs
    • More common in younger women; associated with smoking, higher number of sexual partners and immune compromise
    • Associated with usual type vulvar intraepithelial neoplasia (uVIN)
    • May be associated with genital warts or abnormal Pap smear
    • Progression to SCC in 9 - 16% of untreated and 3% of treated patients
  • Human papillomavirus (HPV) independent:
    • Common in older, postmenopausal women
    • Associated with lichen sclerosus and differentiated type of vulvar intraepithelial neoplasia (dVIN)
    • 3 - 6% of patients develop SCC (J Am Acad Dermatol 1995;32:393)
    • Associated with p53 mutations
    • Increased risk of recurrence and death (Obstet Gynecol 1995;85:709)
Diagrams / tables

Contributed by Priya Nagarajan, M.D., Ph.D.

Schematic for measuring invasion and depth

Clinical features
  • Warty tumor, long standing ulcer, groin mass, plaque or rarely erythematous rash
  • May be asymptomatic, painful or itchy, associated with burning or soreness
  • May be associated with bleeding or discharge
  • Histologic examination is essential to determine type of carcinoma and depth of stromal invasion (most importantly)
  • Therefore, an adequate biopsy is essential
Radiology description
Prognostic factors
  • Clinical adverse prognostic factors include older age, advanced stage at presentation, smoking, ulcerated / matted inguinal lymph nodes (J Skin Cancer 2011;2011:951250)
  • Also clitoral involvement (probably due to larger tumor size), increased depth of invasion, lymphovascular space involvement (associated with metastasis to inguinofemoral lymph nodes) (Eur J Surg Oncol 2015;41:592)
  • Lymph node status: number of positive nodes, extracapsular extension, percentage of nodal replacement and size of nodal metastasis (Crit Rev Oncol Hematol 2012;83:71, Int J Gynecol Cancer 2012;22:503)
  • Perineural invasion is an independent risk factor for recurrence (Am J Surg Pathol 2015;39:1070)
  • Other published indicators of poor prognosis:
    • Tumor size ≥ 6 - 7.9 cm and depth of stromal invasion > 4 mm
    • Tumor size ≥ 8 cm irrespective of depth of stromal invasion
    • Extranodal extension
    • ≥ 2 positive lymph nodes irrespective of tumor size and depth of stromal invasion (Gynecol Oncol 2014;132:643)
    • Tumor size ≥ 35 mm, 15 mm of tumor free surgical margin and depth of stromal invasion > 4 mm (J Gynecol Oncol 2013;24:242)
Case reports
Clinical images

Images hosted on other servers:

Ulcerative lesion, upper labia minor

Gross description
  • Warty tumor, ulcer, plaque or rarely erythematous rash

Superficially invasive squamous cell carcinoma (SISCCA):
  • Previously called microinvasive squamous cell carcinoma but terminology changed based on Lower Anogenital Squamous Terminology (LAST) criteria (Int J Gynecol Pathol 2013;32:76)
  • SISCCA terminology recommended for minimally invasive squamous cell carcinomas of vulva that has been completely excised and can be safely treated with conservative surgical therapy alone
  • SISCCA refers to AJCC T1a (FIGO IA) vulvar cancer:
    • Tumor size ≤ 2 cm, confined to the vulva AND
    • Stromal invasion of ≤ 1 mm
    • No metastasis to lymph nodes
Microscopic (histologic) description
  • Similar to squamous cell carcinoma at other sites
  • However, due to its association with human papillomavirus (HPV), malignant squamous cells may be well differentiated (abundant eosinophilic cytoplasm with low nuclear to cytoplasmic ratio), moderately differentiated (with nuclear pleomorphism) or poorly differentiated (high grade features such as basophilic cytoplasm and increased nuclear to cytoplasmic ratio)
  • For detailed histologic prognostic parameters to be included in the pathology report, please refer to CAP synoptic report: CAP: Cancer Protocol Templates [Accessed 10 October 2017]
  • See also FIGO staging: Int J Gynaecol Obstet 2014;125:97
Microscopic (histologic) images

Contributed by Priya Nagarajan, M.D., Ph.D.


Sqamous cell carcinoma

Squamous cell carcinoma

Squamous cell carcinoma

Sarcomatoid carcinoma

Superficially invasive squamous cell carcinoma (SISCCA):

With VIN


Images hosted on other servers:

Sarcoma-like stroma, various images

Cytology description
  • Performed infrequently (Br J Cancer 2012;106:269, Acta Cytol 1993;37:871)
  • HPV+ neoplasms: clusters or single cells with increased nuclear to cytoplasmic ratio, irregular nuclear contours, coarse chromatin and perinuclear clearing
  • HPV- neoplasms: large cells with round / ovoid nuclei, prominent nucleoli, open / vesicular chromatin, no perinuclear halo
Positive stains
Negative stains
Molecular / cytogenetics description
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