SCCA is a member of serine protease inhibitor (serpins) ovalbumin family at the gene level, which is transcribed by two highly homologous genes, SCCA1 and SCCA2 . At the macromolecular level, SCCA is a sub component of tumor-associated antigens and derived from SCC tissue, which was first isolated from cervical SCC tissue. Elevated SCCA can be detected in SCC of the tongue, esophagus, tonsil, epidermal follicle, lung and uterus. At present, SCCA has become a recognized relatively specific disease-related monitoring index for cervical SCC. It has important clinical significance for the diagnosis, efficacy monitoring and prognosis of the disease, and it is also an important indicator for follow-up of patients with cervical SCC after treatment. The SCCA of the patient we reported was significantly elevated at the time of initial diagnosis, being more than 10 times the upper limit of normal value. During chemoradiotherapy, the lesions regressed satisfactorily, but the SCCA only showed a slow decline and remained at a high level (14.62ng/mL) at the end of treatment. During the subsequent months of outpatient follow-up, it was found that the SCCA remained high (> 10ng/mL) and gradually increased. We first considered the possibility of cervical SCC progression, but no abnormalities were found in related examinations. To further investigate the cause, we performed a whole-body PET/CT scan on the patient and found a metabolically significantly elevated soft tissue shadow in the left maxillary sinus. After surgical resection, the SCCA rapidly dropped to normal (1.49 ng/mL) after surgical excision, and the discovery for SIP recurrence was due to a slow and gradual increase in SCCA after surgery, which again rapidly decreased to normal after the second surgical excision. As a routine and relatively specific indicator of cervical SCC, SCCA appears to be less impact on the progression of cervical SCC, a malignant tumor, than the benign tumor SIP, which leads us to be interested in the possible association between SCCA and cervical SCC and SIP.
SP was first reported in 1854 by Ward and it was thought to originate from schnerderian epithelium located in the sinuses. The cause of the disease is still unknown, but different etiologies have been postulated, including human papilloma virus (HPV) infection, chronic inflammation, environmental pollution and occupational exposure (such as welding fumes, nickel compounds and organic solvents). It usually occurs in the lateral nasal wall, ethmoid sinus, and maxillary sinus, but rarely in the frontal and sphenoid sinuses[17–18]. The disease has the characteristics of destructive growth pattern, high recurrence rate and easy canceration. At present, the preferred treatment is endoscopic sinus inverted papilloma resection . However, even after extensive resection of the tumor, there is still a risk of recurrence or malignancy. Moreover, the recurrence rate (RR) of SIP is also largely affected by the location of tumor growth and invasion. In 2000, Krouse proposed a staging system based on the extent of tumor involvement noted on endoscopic examination of the nasal cavity and imaging examination evaluation . A study has shown that in the Krouse staging system, as the invasion of specific areas from stage I to IV changes, the postoperative RR will gradually increase. Therefore, when the preoperative imaging examination shows that the tumor invades the maxillary sinus, frontal sinus, and sphenoid sinus, the surgeon should pay special attention to the thoroughness of tumor resection and the possibility of postoperative recurrence. The surgical approach also affects the RR of SIP, and the present systematic review indicates that endoscopic approach which has a lower RR is a favorable treatment option compared to external approaches . In addition to these factors, the recurrence rate of SIP is also related to factors such as tumor biological variation . Early diagnosis, treatment and close post-operative follow-up are important for the prognosis of patients. Therefore, it is one of the hot spots to find disease-specific indicators in order to assess the efficacy and timely detection of tumor recurrence. Some studies[23–27] have reported that serum SCCA was elevated in patients with SIP and decreased accordingly after treatment. Yamashita et al.  conducted a study on 30 cases of SIP patients undergoing surgical treatment from January 2006 to January 2015. Among them, 25 patients had elevated SCCA levels, with a median preoperative serum SCCA level of 2.4 ng/mL (interquartile range 1.7–5.2 ng/mL) and 1.0 ng/mL (interquartile range 0.8–1.4 ng/mL) in the postoperative period. There was a statistically significant difference in SCCA levels between the preoperative and postoperative phases of this study (p < 0.001), and it was therefore suggested that SCCA can be used as an indicator for the diagnosis of SIP and for monitoring disease recurrence. Another study showed that preoperative SCCA levels were not associated with the risk of SIP recurrence, while the postoperative SCCA was positively correlated with the risk of disease recurrence (p < 0.001), and that patients with serum SCCA > 1.6ng/mL had a very high probability of tumor recurrence in the further. Therefore, it was recommended that the follow-up frequency should be increased and more comprehensive examination should be carried out for these patients .
Serum SCCA levels correlate with both cervical cancer and SIP, both of which can vary with the occurrence and progression of the disease. However, from the whole course of this patient, cervical cancer, as a malignant tumor, seems to have little impact on the changes of SCCA before and after treatment, while SIP, as a benign tumor, affects the general trend of SCCA level. Therefore, it is difficult to determine whether the treatment effect of cervical SCC is poor or the SCCA level remains high due to SIP only through the serum SCCA level. Serum SCCA levels reflect the total amount of serum SCCA1 and SCCA2, and there may be different mechanisms for elevated serum SCCA in benign tumors and SCC. Yasumatsu et al. reported that SCCA1 was more strongly expressed in SIP tissues than in SCC tissues and, conversely. On the contrary, SCCA2 was predominantly expressed in SCC tissues. The results of this study are consistent with those of previous studies in cervical cancer. Previous studies have found that SCCA2 levels are more strongly expressed in malignant cervical tissues than in normal tissues. Appropriate tumor markers can greatly help clinicians deal with various neoplastic diseases, including SIP and cervical cancer. We can distinguish whether SIP or cervical SCC plays a major role in the increase of serum SCCA concentration by detecting SCCA1 and SCCA2. However, this patient did not detected SCCA1 and SCCA2 because this project did not carry out in our hospital. It is possible that this patient has elevated SCCA1 levels due to SIP, and on the whole, SCCA changes with the condition of SIP.
HPV is a circular double-stranded DNA virus that mainly infects epithelial cells of the skin and mucosal tissue. It is a common pahtogen of sexually transmitted infection, and more than 200 subtypes have been found to exist. According to the carcinogenicity, HPV is divided into high-risk types with carcinogenicity, and low-risk types without carcinogenicity. HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 are the identified high-risk types. The continuous infection of these high-risk HPV is easy to lead to a variety of cancers, especially closely related to the occurrence of cervical cancer. 71% of cervical cancers are caused by infection of HPV 16 and 18. HPV infection is a controversial risk factor for SIP, but is now considered to play an important role in the development of SIP. Gupta et al. summarized 26 studies on HPV infection in SIP patients after April 2012 onwards, a total of 1416 samples of SIP patients were analyzed and 330 cases were found to be HPV positive (23.3%), and the average HPV positive detection rate in SIP patients in different studies ranged from 0–62%. Of the 80 SIP patients reported by Pähler Vor der Holte et al. , 38 cases were HPV positive (38.8%), with the most common HPV genotypes were HPV6 (21/80, 26.3%) and HPV16 (18/80, 22.5%), followed by HPV11 (10/80, 12.5%), HPV58 (4/80, 5%), HPV42 and HPV83 (1/80, 1.3%); they also compared recurrent SP with non-recurrent SP, where the positive detection rate for HPV infection in recurrent and non-recurrent SP were 64.3% (18/28) and 41.9% (36/86), respectively. It can be inferred that HPV infection is a risk factor for SIP and plays a role in promoting the recurrence of SIP, but the detection rate varies greatly among different studies, which is not as clear as the correlation between cervical cancer and HPV. HPV may be transmitted in three ways: sexual transmission, vertical transmission, and extragenital contact. The patient reported in this case was cervical cancer combined with SIP, for which HPV16 was the common risk subtype, and extragenital contact appears to be a more plausible route of transmission for the nasopharyngeal HPV infection in this case, but oral sex has also been reported as a risk factor for HPV transmission. So we speculate that it is possible that the HPV that causes cervical SCC reached the sinus region by some route, causing a local infection that contributed to the development of SIP.
At present, the patient has been followed up for more than 9 months after the second operation. The patient is generally in good condition and the SCCA has been within the normal range, and no abnormalities have been found in relevant examinations. It will be followed up for a longer time to observe the clinical outcome of the patient.
This case gives us some enlightenment: (1) SCCA, as a tumor marker closely associated with cervical SCC, is an important indicator for monitoring changes of cervical SCC. When the change of this indicator is inconsistent with the prognosis of cervical SCC, we should be vigilant about the possibility of combining with other diseases in other sites, especially tumors associated with HPV infection. At the end of radiotherapy and chemotherapy for cervical cancer, when the cervical lesions and pelvic lymph node lesions have resolved satisfactorily but the SCCA is still high, other sites should be promptly investigated for the cause, which may lead to earlier detection and earlier treatment of SIP. (2) When cervical SCC and SIP exist at the same time, it seems that SIP has a greater impact on SCCA than cervical SCC, and that SCCA is more closely related to SIP. Combined with the literature, we recommend that SCCA can be used as a routine monitoring index for SIP. If available, a combination of SCCA1 and SCCA2 can be tried for further judgement. (3) For SIP with a high recurrence rate, can anti-HPV treatment be taken after operation to reduce the risk of recurrence? This may allow the patient to avoid the second surgery within 8 months and its physical and psychological impact on the patient (the patient has a certain impact on the nasal shape after the second operation).