Yonsei Med J.  2014 Mar;55(2):331-338.

Diagnostic Algorithm to Reflect Regressive Changes of Human Papilloma Virus in Tissue Biopsies

• Lhee MJ
• Cha YJ
• Bae JM
• Kim YT
• Cho NH

Abstract

PURPOSE
Landmark indicators have not yet to be developed to detect the regression of cervical intraepithelial neoplasia (CIN). We propose that quantitative viral load and indicative histological criteria can be used to differentiate between atypical squamous cells of undetermined significance (ASCUS) and a CIN of grade 1.
MATERIALS AND METHODS
We collected 115 tissue biopsies from women who tested positive for the human papilloma virus (HPV). Nine morphological parameters including nuclear size, perinuclear halo, hyperchromasia, typical koilocyte (TK), abortive koilocyte (AK), bi-/multi-nucleation, keratohyaline granules, inflammation, and dyskeratosis were examined for each case. Correlation analyses, cumulative logistic regression, and binary logistic regression were used to determine optimal cut-off values of HPV copy numbers. The parameters TK, perinuclear halo, multi-nucleation, and nuclear size were significantly correlated quantitatively to HPV copy number.
RESULTS
An HPV loading number of 58.9 and AK number of 20 were optimal to discriminate between negative and subtle findings in biopsies. An HPV loading number of 271.49 and AK of 20 were optimal for discriminating between equivocal changes and obvious koilocytosis.
CONCLUSION
We propose that a squamous epithelial lesion with AK of >20 and quantitative HPV copy number between 58.9-271.49 represents a new spectrum of subtle pathological findings, characterized by AK in ASCUS. This can be described as a distinct entity and called "regressing koilocytosis".

Keyword

HPV; loading concentration; ASCUS; CIN; regressing koilocytosis

MeSH Terms

Biopsy*
Cervical Intraepithelial Neoplasia
Female
Humans*
Inflammation
Logistic Models
Methods
Papilloma*
Viral Load
Viruses*

Figure

• 

  Fig. 1 Microscopic examination of biopsied specimens: the spectrum of koilocytosis is variable between abortive and typical koilocytosis, from the diagnosis of CNI, cervical epithelia within normal limits or chronic inflammation (a), to CIN1, cervical intraepithelial neoplasm 1 (g), depending on whether the cell meets all the criteria of an acentric, hyperchromatic, moderately enlarged nucleus (c) displaced by a large perinuclear halo (f) or multinucleation (e). Other variables such as keratohyaline granules (b) and dyskeratosis, presumed to be inflammatory effects (d), were noted occasionally. AK, abortive koilocyte; TK, typical koilocyte.

• 

  Fig. 2 Receiver operating characteristic (ROC) curves of log (HPV), AK, and a priori for age, for discrimination between (A) negative (0) and equivocal findings (1, 2); and (B) equivocal changes (0, 1) and obvious koilocytosis (2) in biopsies. AK, abortive koilocyte; HPV, human papilloma virus.

• 

  Fig. 3 Diagnostic algorithm for abnormal squamous cell lesions. Optimal cut-off values for ASCUS: regressing koilocytes matched ASCUS in the quantitative HPV copy number over the range of 58.9-271.49 when more than 20 AKs were detected.⊖, the cases which do not meet any of the above three criteria;⊕, the cases which meet only one of the above three criteria;, the cases which meet two of the above three criteria;, the cases which meet all of the above three criteria. ASCUS, atypical squamous cells of undetermined significance; AK, abortive koilocyte; TK, typical koilocyte; HC, hybrid capture; CNI, cervical epithelia within normal limits or chronic inflammation; CIN1, cervical intraepithelial neoplasm 1; LR HPV, low risk human papilloma virus.

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