I have read on Reich and Regauer, Int J Gyn Pathol 2016;36:71 that there are cervical cancers not associated with HPV and these are characterized by being thin (max 9 cell layers), without LSIL precursors and koilocytes. Of course, the tissues do not stain for HPV products.
Is there more literature on HPV-negative cervical cancer? Is it possible to discriminate histologically these types of cancer?
Thank you
A negative test result can be attributed to a variety of reasons, which of several could give false-negative results. One of them is tumor sample quality, which is of importance, especially when working with formalin-fixed paraffin-embedded material wherein protein cross binding and nucleic acid degradation over time could affect the analysis (Ludyga N, Grunwald B, Azimzadeh O, et al. Nucleic acids from long-term preserved FFPE tissues are suitable for downstream analyses. Virchows Arch 2012;460:131–40).
It has previously been described that loss of the frequently targeted viral L1 gene after viral integration could be a reason for HPV-negative test results (Walboomers JM, Meijer CJ. Do HPV-negative cervical carcinomas exist. J Pathol 1997;181:253–4).
The prognosis difference between HPVpositive and negative CC seems to depend on histology rather than HPV status (HPV-negative Tumors in a Swedish Cohort of Cervical Cancer Malin Kaliff, M.Sc., Mats G. Karlsson, M.D., Ph.D., Bengt Sorbe, M.D., Ph.D., Louise Bohr Mordhorst, M.D., Ph.D., Gisela Helenius, Ph.D., and Gabriella Lillsunde-Larsson, Ph.D., Int J Gynecol Pathol Vol. 39, No. 3, May 2020).
HPV negative cervical cancer is rare when talking about squamous cell carcinomas, but represents 10 to 15% of cervical adenocarcinomas. In scc and adc, p16 immunohistochemistry is an excellent surrogate marker of hpv induced lesions, with a nearly 100% correlation with ISH. Certain morphologic subtypes of adenocarcinomas are known to be hpv independant, for instance gastric type adc or clear cell adc.
Check the WHO classification of female genital tumours (2020), as it is the reference classification used worldwide by pathologists to diagnose these entities.
A frequently used biomarker is p16 INK4a. Others are HPV16, 18-E6/E7 mRNAs which can be detected in tissue samples using PCR.
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