Discussion
We encountered a case in which a condyloma-like papillary tumor was
repeatedly treated as condyloma; however, there was repeated recurrence.
Therefore, the patient was re-diagnosed and treated for non-invasive
cervical cancer with HPV6 infection. In 1986, Randall reported nine
cases of PSCC for the first time worldwide. The characteristic
pathological finding of PSCC is full-thickness dysplasia cells in a
papillary architecture with fibrovascular cores and an invasive
component that is usually deep to the papillary
excrescences.2 Colposcopy findings of PSCC are
characterized by the development of a condyloma-like mass with exophytic
growth.1 However, they clearly distinguished PSCC from
squamous papilloma, condyloma, and verrucous
carcinoma.2 Compared to conventional SCC, PSCC is
characterized by slow progression of lesions. In addition, the
possibility that PSCC is different from traditional SCC, in terms of the
high frequency of late metastasis and recurrence, is also
indicated.3 For instance, Randall reported that two
cases of PSCC recurred over more than 7 years (87 months and 106 months)
after resection, and Koenig also reported vaginal recurrence of PSCC 12
years after the initial diagnosis.2,3 Because PSCC is
a rare histological type, the treatment strategy is the same as that for
conventional SCC.1,3
In this case, treatment for condyloma was performed several times for
non-invasive PSCC. However, despite inadequate treatment for
non-invasive PSCC, the tumor did not invade or spread, indicating slow
progression of PSCC, as previously reported.1It is also known that PSCC is
difficult to be diagnosed preoperatively. Nagura et al. reported 28
cases of PSCC diagnosed by colposcopic biopsy, of which 12 (43%) were
true PSCC and the other cases were non-keratinized or microinvasive
SCC.1 They also reported that PSCC is difficult to be
diagnosed via biopsy specimens because of the degree of stromal
invasion. If MRI shows stromal invasion of ≥ 3 mm,
radical hysterectomy or radical
trachelectomy is considered. It has been reported that conization or
simple hysterectomy is considered if stromal invasion of ≤ 3 mm is
suspected on MRI.1
It is also necessary to pay attention to the difficulty in diagnosis and
pitfalls, and it is necessary to consider PSCC when an intractable
condyloma-like mass is observed. Additionally, it is necessary to
consider a re-diagnosis of the pathology if PSCC is suspected. It has
been reported that the positive rate of high-risk HPV in PSCC is lower
than that in cases of conventional SCC (50% vs. > 95%).
High-risk HPV positivity in PSCC is often associated with type
16.4,5 Immunochemistry data from previous reports
showed that the expression of Ki 67, p 63, and p 16 is higher in PSCC
than in condyloma.6,7 A strong positive result for p
16 was also observed in our case. We performed high-risk HPV screening
tests several times before surgery, but they were negative; HPV6 was
identified by HPV DNA genotyping of tumor samples after surgery. Sixteen
HPV infections were specifically detected in cryosurgery specimens using
the PapiPlexTM method. To the best of our knowledge, this is the first
report of HPV6 infection in PSCC. The possibility of HPV6 infection in a
high-risk HPV-negative case in a previous report has been indicated.
Although HPV6 is not a high-risk HPV, a report showed that HPV6
infection was observed in CIN 2/3, 8 and a report of
laryngeal cancer reported integration of HPV6 causing malignant
transformation.9 It is considered that HPV6 infection
can be a cause of non-invasive PSCC based on the above report and the
slow progress in this case.
From the above, it is possible that the mechanisms of generation and
progress of PSCC and conventional SCC are different. However, further
investigation is necessary in the future.