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KUANetal.

TABLE XXI.B.3 Evidence for HPV, molecular markers, and genetic studies in IP, IP-SCC, and DN-SCC.

Clinical endpoints

Study

Year LOE Study design Study groups

Conclusion

Lawson et al. 657

2008 2

Systematic review

887 cases

HPV detection rates

1. HPV detection varies widely 2. Similar detection rates across methods (26.8%, 25.2%, 23.6%) 3. HPV more often detected in malignant (55.1%) and recurrent tumors (57.9%) 1. High-risk HPV in 11 out of 146 (7.5%) 2. EGFR mutation in 13 out of 14 IP-SCCs 3. EGFR mutation in eight out of 132 DN-SCCs 4. No KRAS mutation detected 5. EGFR copy number gain in 41 out of 146 6. EGFR , EGFR copy number gain, and high-risk HPV are mutually exclusive 1. Subset of IPs had low-risk HPV 2. Low-risk HPV is mutually exclusive with EGFR mutations 3. All IPs and IP-SCCs negative for p16 and high-risk HPV 4. Three out of five (60%) IP-SCCs with low-risk HPV 5. Five of seven (71.4%) DN-SCCs with p16 and high-risk HPV 6. 11 out of 15 (73.3%) IPs with negative HPV had EGFR exon19 or 20 mutation 1. HPV in 0 out of 52 IPs or IP-SCCs 2. HPV in two of seven DN-SCCs 3. Transcriptionally active high-risk HPV does not play a role in IP or malignant transformation 1. All IPs and IP-SCCs demonstrated EGFR mutation or HPV HPVand EGFR are mutually exclusive except one case 1. High-risk HPV more often found in DN-SCC (28.6% vs. 4.5%) 2. Low-risk HPV found in IP-SCC (18.2% vs. 0%) 3. IP progression to IP-SCC associated with HPV and absenceof EGFR 4. EGFR mutation and HPV infection may represent

Hongo et al. 672

2021

3

Retrospective cohort

14 IP-SCCs, 132 DN-SCCs

1. Mutational

status ( EGFR , KRAS )

2. HPV status

Mehrad et al. 666

2020 3

Retrospective cohort

39 IPs, five IP-SCCs, seven DN-SCCs

1. Mutational

status (EGFR, p16)

2. HPV status

Rooper et al. 662

2017 3

Retrospective cohort

30 IPs without

Role of HPV in

dysplasia, six IPs with dysplasia, 14 IP-SCCs (synchronous), two IP-SCCs (metachronous), seven DN-SCCs 58 IPs, 22 IP-SCCs with 13 matched with IPs, 14DN-SCCs

IP and IP-SCC

Udager et al. 667

1. Mutational

2018 3

Retrospective cohort

status ( EGFR , KRAS )

2. HPV status

alternative oncogenic mechanism in IP-SCC

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