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.